Extending Innovation From Lymphoma to Myeloma: The Next Wave of Bispecific Antibody Breakthroughs for Clinical Care
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Jun 27, 2024
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About This Presentation
Chair and Presenter, Sundar Jagannath, MD, FASCO, Sabarish Ayyappan, MD, and Jennifer Crombie, MD, discuss lymphoma and myeloma in this CME/MOC/NCPD/AAPA/IPCE activity titled “Extending Innovation From Lymphoma to Myeloma: The Next Wave of Bispecific Antibody Breakthroughs for Clinical Care.” Fo...
Slide Content
Extending Innovation From
Lymphoma to Myeloma
The Next Wave of Bispecific Antibody Breakthroughs
for Clinical Care
Sabarish Ayyappan, MD =)
Clinical Associate Professor and Medical We W
Director of Hematologic Malignancies a
City of Hope Atlanta =
Sundar Jagannath, MD, FASCO E o Georgia aad
Professor of Medicine WA }
a
Icahn School of Medicine at Mount Sinai
New York, New York Jennifer Crombie, MD
he Assistant Professor of Medicine,
Harvard Medical School
Dana-Farber Cancer Institute
Boston, Massachusetts
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2024, PeerView
Lymphoma to Myeloma
The Next Wave of Bispecific Antibody Breakthroughs
for Clinical Care
Sabarish Ayyappan, MD =)
Clinical Associate Professor and Medical We W
Director of Hematologic Malignancies a
City of Hope Atlanta =
Sundar Jagannath, MD, FASCO E o Georgia aad
Professor of Medicine WA }
a
Icahn School of Medicine at Mount Sinai
New York, New York Jennifer Crombie, MD
he Assistant Professor of Medicine,
Harvard Medical School
Dana-Farber Cancer Institute
Boston, Massachusetts
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2024, PeerView
In Multiple Myeloma, an Ongoing Need to Integrate Modern
Therapy in Triple-Class-Exposed (TCE) Settings
Estimate of Time to Discontinuation
Cohen MM Events Censored _Madhan (95% C0)
Tce zum 134 1498 10002108)
TOR 64 (6088)
pe a ss 186987)
PETCR 74 45 MO 6206587)
Medicare and Medicaid Claims Data
for Patients With MM from November
14, 2006-December 31, 20201
An increased use of standard
therapies over multiple LOT led
N = 2,830 TCE; 1,371 triple-class
to more rapid discontinuation
refractory (TCR); 1,121 penta-
exposed (PE); and 774 PE-TCR
patients
Probability of Remaining on Treatment
TTD, TTNT, and OS were short
and healthcare resource
Time, mo
utilization and costs were high A need for better therapies in RR and TCR
myeloma—what is the role of bispecifics?
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1. Delea Total. ASH 2023. Abstract 3773
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Therapy in Triple-Class-Exposed (TCE) Settings
Estimate of Time to Discontinuation
Cohen MM Events Censored _Madhan (95% C0)
Tce zum 134 1498 10002108)
TOR 64 (6088)
pe a ss 186987)
PETCR 74 45 MO 6206587)
Medicare and Medicaid Claims Data
for Patients With MM from November
14, 2006-December 31, 20201
An increased use of standard
therapies over multiple LOT led
N = 2,830 TCE; 1,371 triple-class
to more rapid discontinuation
refractory (TCR); 1,121 penta-
exposed (PE); and 774 PE-TCR
patients
Probability of Remaining on Treatment
TTD, TTNT, and OS were short
and healthcare resource
Time, mo
utilization and costs were high A need for better therapies in RR and TCR
myeloma—what is the role of bispecifics?
PeerView.com
1. Delea Total. ASH 2023. Abstract 3773
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
During the Modern Rituximab Era,
Outcomes Were Poor in R/R DLBCL'
Events Median, mo
n Everts Medanme 0
Bo. = 20) — Payer aa 71
Zu Au 505608 63 Bond] — Retracomtozloriaterine 2611906 61
dz nee à
Bo
Es \
Ea
Timo From Start of Salvage Therapy, mo Time From Start of Salvage Therapy, mo refractory disease was
months
E
E Has the emergence of
— No u 54
immunotherapy
(CAR-T and bispecific
antibodies) changed
this picture?
A From tata Salvage Therapy, mo
1. Crump M et al Blood. 2017:130:1800-1808, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Outcomes Were Poor in R/R DLBCL'
Events Median, mo
n Everts Medanme 0
Bo. = 20) — Payer aa 71
Zu Au 505608 63 Bond] — Retracomtozloriaterine 2611906 61
dz nee à
Bo
Es \
Ea
Timo From Start of Salvage Therapy, mo Time From Start of Salvage Therapy, mo refractory disease was
months
E
E Has the emergence of
— No u 54
immunotherapy
(CAR-T and bispecific
antibodies) changed
this picture?
A From tata Salvage Therapy, mo
1. Crump M et al Blood. 2017:130:1800-1808, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Response Duration and Survival Shortens
After Each Relapse’
There’s a Clear Need for Newer Therapies in the FL Salvage Setting
100 Response Duration
= 80 =
E E
a 2
30 ö
5 5
2 2
3 « 3
3
2 2,
a à
— Eton ment — rrstine voatnent
— Scone vosiment = — Score weatment
— Third.ine treatment Fr —— Thirddine treatment
0 0
0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16
Time, y Is immunotherapy making Time, y
1. Rivas-Delgado A at al. Br Hoemalol 2019:184:753-789, a difference in FL? PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
After Each Relapse’
There’s a Clear Need for Newer Therapies in the FL Salvage Setting
100 Response Duration
= 80 =
E E
a 2
30 ö
5 5
2 2
3 « 3
3
2 2,
a à
— Eton ment — rrstine voatnent
— Scone vosiment = — Score weatment
— Third.ine treatment Fr —— Thirddine treatment
0 0
0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16
Time, y Is immunotherapy making Time, y
1. Rivas-Delgado A at al. Br Hoemalol 2019:184:753-789, a difference in FL? PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Bispecific Antibodies Represent a Step Forward in MM
Regulatory Status
Teclistamab
BCMA x CD3
Elranatamab Approved in RRMM after 24 lines of prior therapy,
BCMA x CD3 including an IMiD, a PI, and an anti-CD38 antibody
Talquetamab
GPRC5D x CD3
Linvoseltamab FDA priority review for patients with RRMM who have
BCMA x CD3 received 23 lines of prior therapy; phase 3 testing
ABBV-383
BCMA x CD3
Download the
Practice Aid!
PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Regulatory Status
Teclistamab
BCMA x CD3
Elranatamab Approved in RRMM after 24 lines of prior therapy,
BCMA x CD3 including an IMiD, a PI, and an anti-CD38 antibody
Talquetamab
GPRC5D x CD3
Linvoseltamab FDA priority review for patients with RRMM who have
BCMA x CD3 received 23 lines of prior therapy; phase 3 testing
ABBV-383
BCMA x CD3
Download the
Practice Aid!
PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Bispecific Antibodies Represent a Step Forward in NHL
Regulatory Status in the US
Approved in R/R DLBCL NOS, including DLBCL arising from
Econ indolent lymphoma, and high-grade B-cell lymphoma after
22 lines of prior therapy
Glofitamab Approved in R/R DLBCL, NOS, or LBCL arising from FL, after
CD20 x CD3 22 lines of systemic therapy
Mosunetuzumab o A 4
CD20 x CD3 Approved for adults with R/R FL after 22 lines of systemic therapy
Odronextamab gi
CD20 x CD3 Phase 3 testing
Combination platforms with bispecifics and other antibodies po
(eg, mosunetuzumab or glofitamab + polatuzumab vedotin) — IMA
are being rapidly developed
PeerVie
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Regulatory Status in the US
Approved in R/R DLBCL NOS, including DLBCL arising from
Econ indolent lymphoma, and high-grade B-cell lymphoma after
22 lines of prior therapy
Glofitamab Approved in R/R DLBCL, NOS, or LBCL arising from FL, after
CD20 x CD3 22 lines of systemic therapy
Mosunetuzumab o A 4
CD20 x CD3 Approved for adults with R/R FL after 22 lines of systemic therapy
Odronextamab gi
CD20 x CD3 Phase 3 testing
Combination platforms with bispecifics and other antibodies po
(eg, mosunetuzumab or glofitamab + polatuzumab vedotin) — IMA
are being rapidly developed
PeerVie
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Our Goals for Today
Improve your knowledge of current evidence supporting the integration of
emerging bispecific antibodies in MM and lymphoma
Enhance your skills for preparing treatment plans that anticipate a role for
emerging bispecific options across multiple lines of therapy in NHL settings
Augment your ability to integrate emerging bispecific antibody options into
sequential management plans for patients with RRMM
Provide you with guidance on strategies to address unique aspects of
care associated with the use of next-generation bispecific antibodies,
including safety and dosing considerations
PeerView.com/KQE827
Improve your knowledge of current evidence supporting the integration of
emerging bispecific antibodies in MM and lymphoma
Enhance your skills for preparing treatment plans that anticipate a role for
emerging bispecific options across multiple lines of therapy in NHL settings
Augment your ability to integrate emerging bispecific antibody options into
sequential management plans for patients with RRMM
Provide you with guidance on strategies to address unique aspects of
care associated with the use of next-generation bispecific antibodies,
including safety and dosing considerations
PeerView.com/KQE827
Next Steps in Lymphoma—
Bispecifics on the Move
DLBCL
Sabarish Ayyappan, MD
Clinical Associate Professor and Medical Director of
Hematologic Malignancies
City of Hope Atlanta
Atlanta, Georgia
Copyright © 2000-2024, PeerView
Bispecifics on the Move
DLBCL
Sabarish Ayyappan, MD
Clinical Associate Professor and Medical Director of
Hematologic Malignancies
City of Hope Atlanta
Atlanta, Georgia
Copyright © 2000-2024, PeerView
(2) Workshop: A Patient With R/R DLBCL and
Prior Exposure to CAR-T
65-year-old patient with DLBCL NOS treated with R-CHOP and achieves complete
response (CR) confirmed by PET-CT (PS of 1).
+ 6 months post treatment, he shows signs of relapse and is referred for CAR-T and
achieves a remission; after 6 months, he is found to have progression based on
imaging. Biopsy proven to be DLBCL NOS.
PeerView.com
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Prior Exposure to CAR-T
65-year-old patient with DLBCL NOS treated with R-CHOP and achieves complete
response (CR) confirmed by PET-CT (PS of 1).
+ 6 months post treatment, he shows signs of relapse and is referred for CAR-T and
achieves a remission; after 6 months, he is found to have progression based on
imaging. Biopsy proven to be DLBCL NOS.
PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
(&) Workshop: A Patient With R/R DLBCL and
Prior Exposure to CAR-T
65-year-old patient with DLBCL NOS treated with R-CHOP and achieves complete
response (CR) confirmed by PET-CT (PS of 1).
+ 6 months post treatment, he shows signs of relapse and is referred for CAR-T and
achieves a remission; after 6 months, he is found to have progression based on
imaging. Biopsy proven to be DLBCL NOS.
Points to consider
+ Is there life after CAR-T failure?
+ Current experience with step-up and subsequent dosing with epcoritamab
and glofitamab
+ Role of emerging bispecifics (odronextamab)
PeerView.com
Peerview.com/KQE827 Copyright © 2000-2024, PeerView
Prior Exposure to CAR-T
65-year-old patient with DLBCL NOS treated with R-CHOP and achieves complete
response (CR) confirmed by PET-CT (PS of 1).
+ 6 months post treatment, he shows signs of relapse and is referred for CAR-T and
achieves a remission; after 6 months, he is found to have progression based on
imaging. Biopsy proven to be DLBCL NOS.
Points to consider
+ Is there life after CAR-T failure?
+ Current experience with step-up and subsequent dosing with epcoritamab
and glofitamab
+ Role of emerging bispecifics (odronextamab)
PeerView.com
Peerview.com/KQE827 Copyright © 2000-2024, PeerView
Relapsed DLBCL
3L+ DLBCL Patients Have a Poor Prognosis*?
Post-CAR-T Progression Has
Poor Survival?
Event-Free Survival Overall Survival by LOT Overall Survival
10
1 venta Medan, mo
22 D ete ‘0 sedans
go 261008 61 Dom aL 160 (105242)
Rola st2mopostascr Wut 62 E
Bor 3 07
zos 3 05
go é 2 gos
eos moe 8 =
Boe eric u re os
Gor elapsed s12 mo postASCT
o o o
0 À © © © wo mo mo no wo on me à © À 9 wo 20 0 E)
Time From Start of Salvage Therapy, mo Time From Index, mo it
No. at Risk Time, d
ME HAT IQ 799 519 285 03 O No.at Rik
a ‘wo 6 8 3 18 0 O0 A Me 73 4 Ok
WOW 4 i 7 2 0 0
a S 8 2 0 0 0 «©
1. Crump M et al. Blood. 2017:130:1800-1808.2. Sineshaw H etal. Cancer Med. 2024;19:7 173.3. Spiegel Jet al. Blood. 2021:137:1832-1835. PeerView.com
PeerView.com/KQE827
Copyright © 2000-2024, PeerView
3L+ DLBCL Patients Have a Poor Prognosis*?
Post-CAR-T Progression Has
Poor Survival?
Event-Free Survival Overall Survival by LOT Overall Survival
10
1 venta Medan, mo
22 D ete ‘0 sedans
go 261008 61 Dom aL 160 (105242)
Rola st2mopostascr Wut 62 E
Bor 3 07
zos 3 05
go é 2 gos
eos moe 8 =
Boe eric u re os
Gor elapsed s12 mo postASCT
o o o
0 À © © © wo mo mo no wo on me à © À 9 wo 20 0 E)
Time From Start of Salvage Therapy, mo Time From Index, mo it
No. at Risk Time, d
ME HAT IQ 799 519 285 03 O No.at Rik
a ‘wo 6 8 3 18 0 O0 A Me 73 4 Ok
WOW 4 i 7 2 0 0
a S 8 2 0 0 0 «©
1. Crump M et al. Blood. 2017:130:1800-1808.2. Sineshaw H etal. Cancer Med. 2024;19:7 173.3. Spiegel Jet al. Blood. 2021:137:1832-1835. PeerView.com
PeerView.com/KQE827
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+ T-cell engager therapy
In DLBCL, Bispecific Antibodies Are Among the
Recommended Sequential Options After 23 LOT!
Third-Line and Subsequent Therapy
Other recommended regimens
+ Loncastuximab tesirine-Ipyl
+ Selinexor (including patients with disease progression after
transplant or CAR T-cell therapy)
Prefe imen:
© CAR T-cell therapy
(preferred if not previously given) (in alphabetical order)
> Axicabtagene ciloleucel (CD19-directed)
> Lisocabtagene maraleucel (CD19-directed)
> Tisagenlecleucel (CD19-directed)
Bispecific antibody therapy (only after at least two lines of
systemic therapy, including patients with disease
progression after transplant or CAR T-cell therapy)
(in alphabetical order)
© Epcoritamab-bysp
© Glofitamab-gxbm
Polatuzumab vedotin-piig + bendamustine + rituximab
= + Tafasitamab-cxix + lenalidomide
Options In A but could + Brentuximab vedotin + lenalidomide for CD30+ disease
+ Ibrutinib (non-GCB DLBCL)
Lenalidomide + rituximab (non-GCB DLBCL)
1.NCCN Clinical Practice Guidelines in Oncology: B-Call Lymphomas. Version 2.2024. hps:/wmw.ncen orglprofessionalsphysician_glsptb-col pat PeerView.com
PeerView.com/KQE827
Copyright © 2000-2024, PeerView
In DLBCL, Bispecific Antibodies Are Among the
Recommended Sequential Options After 23 LOT!
Third-Line and Subsequent Therapy
Other recommended regimens
+ Loncastuximab tesirine-Ipyl
+ Selinexor (including patients with disease progression after
transplant or CAR T-cell therapy)
Prefe imen:
© CAR T-cell therapy
(preferred if not previously given) (in alphabetical order)
> Axicabtagene ciloleucel (CD19-directed)
> Lisocabtagene maraleucel (CD19-directed)
> Tisagenlecleucel (CD19-directed)
Bispecific antibody therapy (only after at least two lines of
systemic therapy, including patients with disease
progression after transplant or CAR T-cell therapy)
(in alphabetical order)
© Epcoritamab-bysp
© Glofitamab-gxbm
Polatuzumab vedotin-piig + bendamustine + rituximab
= + Tafasitamab-cxix + lenalidomide
Options In A but could + Brentuximab vedotin + lenalidomide for CD30+ disease
+ Ibrutinib (non-GCB DLBCL)
Lenalidomide + rituximab (non-GCB DLBCL)
1.NCCN Clinical Practice Guidelines in Oncology: B-Call Lymphomas. Version 2.2024. hps:/wmw.ncen orglprofessionalsphysician_glsptb-col pat PeerView.com
PeerView.com/KQE827
Copyright © 2000-2024, PeerView
DLBCL Third-Line Treatment Landscape in 2024
Third-Line DLBCL
Axicabtagene
Lisocabtagene
Tisagenlecleucel
Epcoritamab
Glofitamab
Polatuzumab-BR
Selinexor
Salvage
chemotherapy
PeerView.com/KQE827
Tafasitamab +
Lenalidomide
Loncastuximab
PeerView.com
Copyright © 2000-2024, PeerView
Third-Line DLBCL
Axicabtagene
Lisocabtagene
Tisagenlecleucel
Epcoritamab
Glofitamab
Polatuzumab-BR
Selinexor
Salvage
chemotherapy
PeerView.com/KQE827
Tafasitamab +
Lenalidomide
Loncastuximab
PeerView.com
Copyright © 2000-2024, PeerView
Bispecific Antibodies in DLBCL
specific Format co?
CD3 Ratio
4 A Knobs into hole ps
= Glofitamab Y IgG1 (different fabs) Zi
© Epcoritamab Y 1gG1 Head to tail fusion #1
D = ES
e Controlled E
Odronextamab MY 1961 Fab-armexchange 1:1
Wetec mty
Heavy chains with
Mosunetuzumab y 1964 different affinity a
PeerView.com
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specific Format co?
CD3 Ratio
4 A Knobs into hole ps
= Glofitamab Y IgG1 (different fabs) Zi
© Epcoritamab Y 1gG1 Head to tail fusion #1
D = ES
e Controlled E
Odronextamab MY 1961 Fab-armexchange 1:1
Wetec mty
Heavy chains with
Mosunetuzumab y 1964 different affinity a
PeerView.com
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Phase I/II EPCORE NHL-1 Trial Evaluating SC Epcoritamab
Monotherapy for R/R B-Cell NHL After 22 Lines of Therapy!
N = 157
+ Median lines: 3 (2-11)
y Primary refractory: 61%, 39% prior CAR-T, and
74% refractory to CAR-T
+ Median time to response: 1.4 mo (range: 1.0:
+ Median time to CR: 2.7 mo (range: 1.2-16.3)
-8.4)
Results
Y ORR: 61% for DLBCL and HGBCL, 63% for
LBCL; 39% CR rate in both groups
+ Median DOR was 15.5 mo (if CR, median DOR:
20.8 mo in both groups)
Y Median PFS was 4.4 mo (95% Cl, 3.0-7.9)
Y Median OS was not reached (95% Cl, 11.3-NR)
1. ThieblemontC et al. J Clin Oncol 2023:41:2238-2247.
PeerView.com/KQE827
WORmPRuSD = PD [PH CART ool
100
Es 75
E? so
PE
$
Patients
100
80
60 PFS
40
20
o
o 3 6 3 12
Time, mo
No, at Risk
a aer 6 s 2 s
PeerView.com
Copyright © 2000-2024, PeerView
Monotherapy for R/R B-Cell NHL After 22 Lines of Therapy!
N = 157
+ Median lines: 3 (2-11)
y Primary refractory: 61%, 39% prior CAR-T, and
74% refractory to CAR-T
+ Median time to response: 1.4 mo (range: 1.0:
+ Median time to CR: 2.7 mo (range: 1.2-16.3)
-8.4)
Results
Y ORR: 61% for DLBCL and HGBCL, 63% for
LBCL; 39% CR rate in both groups
+ Median DOR was 15.5 mo (if CR, median DOR:
20.8 mo in both groups)
Y Median PFS was 4.4 mo (95% Cl, 3.0-7.9)
Y Median OS was not reached (95% Cl, 11.3-NR)
1. ThieblemontC et al. J Clin Oncol 2023:41:2238-2247.
PeerView.com/KQE827
WORmPRuSD = PD [PH CART ool
100
Es 75
E? so
PE
$
Patients
100
80
60 PFS
40
20
o
o 3 6 3 12
Time, mo
No, at Risk
a aer 6 s 2 s
PeerView.com
Copyright © 2000-2024, PeerView
Dosing Principles for SC Epcoritamab in DLBCL'
Treatment Cycle? Day Dose of Epcoritamab, mg
1 Step-up dose 1 | 0.16
8 Step-up dose 2 0.8
Cycle 1
15 First full dose — | 48
22 48
Cycles 2 and 3 1, 8, 15, and 22 48
Cycles 4 to 9 1 and 15 48
Cycles 10+ 1 48
* Patients should be hospitalized for 24 hours after administration
of the cycle 1 day 15 dosage of 48 mg
+ Administer premedication and prophylaxis as recommended ee
ractice Aid!
+ Dosages of 0.16 mg and 0.8 mg require dilution prior to
administration
2 28 day oye ES
1. Epkily(epcortamab-bysp) Prescrbing Information. https ww accessdata (da govidrugsatda_docsiabel2023/76 13245000 pa PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Treatment Cycle? Day Dose of Epcoritamab, mg
1 Step-up dose 1 | 0.16
8 Step-up dose 2 0.8
Cycle 1
15 First full dose — | 48
22 48
Cycles 2 and 3 1, 8, 15, and 22 48
Cycles 4 to 9 1 and 15 48
Cycles 10+ 1 48
* Patients should be hospitalized for 24 hours after administration
of the cycle 1 day 15 dosage of 48 mg
+ Administer premedication and prophylaxis as recommended ee
ractice Aid!
+ Dosages of 0.16 mg and 0.8 mg require dilution prior to
administration
2 28 day oye ES
1. Epkily(epcortamab-bysp) Prescrbing Information. https ww accessdata (da govidrugsatda_docsiabel2023/76 13245000 pa PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Glofitamab for Relapsed or Refractory DLBCL'
Duration of CR Among Patients With CR in the
N= 155 100 Main Analysis Cohort
e 80
Y Median lines: 3 (2-7) te 60
Y Primary refractory: 58%, 33% prior CAR-T, 22 40
and 30% refractory to CAR-T SE 20
Y Median time to CR: 42 d o
Y Median follow-up: 18.2 mo 012345678 9 101112131415161718192021
No. at Risk Time, mo
Results MON 97 35 4645 06 4 20 28 26 29 021 18 1419 12 10 10 2 1 0
Y ORR: 52% with 40% CR 100 PFS in the Main Analysis Cohort
Y Median DOR was 18 mo 2 * 80
(if CR, median DOR: 26.2 mo) 38 60
y Median PFS: 4.9 mo (95% Cl, 3.4-8.1) ES 40
y 12-mo OS: 50% (95% Cl, 41-58) de 2
à o 3 6 9 12 15 18 21 24
No. at Risk Time, mo
MURS art
1. Dickinson Meta. N Engl Mod. 2022:387.2220-2231 PeerView.com
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Duration of CR Among Patients With CR in the
N= 155 100 Main Analysis Cohort
e 80
Y Median lines: 3 (2-7) te 60
Y Primary refractory: 58%, 33% prior CAR-T, 22 40
and 30% refractory to CAR-T SE 20
Y Median time to CR: 42 d o
Y Median follow-up: 18.2 mo 012345678 9 101112131415161718192021
No. at Risk Time, mo
Results MON 97 35 4645 06 4 20 28 26 29 021 18 1419 12 10 10 2 1 0
Y ORR: 52% with 40% CR 100 PFS in the Main Analysis Cohort
Y Median DOR was 18 mo 2 * 80
(if CR, median DOR: 26.2 mo) 38 60
y Median PFS: 4.9 mo (95% Cl, 3.4-8.1) ES 40
y 12-mo OS: 50% (95% Cl, 41-58) de 2
à o 3 6 9 12 15 18 21 24
No. at Risk Time, mo
MURS art
1. Dickinson Meta. N Engl Mod. 2022:387.2220-2231 PeerView.com
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Dosing Principles for IV Glofitamab in DLBCL'
Treatment Cycle? Day Dose of Glofitamab, mg
1 Obinutuzumab 1,000
Cycle 1 8 Step-up dose 1 25
15 Step-up dose 2 10
Cycles 2-12 1 30
221 day.
orde.
1 ips vin accossdata da govidrugsatida_ docslabo/2023/761300:00000 pat.
PeerView.com/KQE827
+ Pretreat with a single 1,000-mg dose of obinutuzumab IV 7 days before
initiation of glofitamab (cycle 1 day 1)
+ Patients should be hospitalized for the 2.5 mg step-up dose and for
subsequent infusions as recommended
+ Administer premedication as recommended ee
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Treatment Cycle? Day Dose of Glofitamab, mg
1 Obinutuzumab 1,000
Cycle 1 8 Step-up dose 1 25
15 Step-up dose 2 10
Cycles 2-12 1 30
221 day.
orde.
1 ips vin accossdata da govidrugsatida_ docslabo/2023/761300:00000 pat.
PeerView.com/KQE827
+ Pretreat with a single 1,000-mg dose of obinutuzumab IV 7 days before
initiation of glofitamab (cycle 1 day 1)
+ Patients should be hospitalized for the 2.5 mg step-up dose and for
subsequent infusions as recommended
+ Administer premedication as recommended ee
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CRS/ICANS Risk With Epcoritamab and Glofitamab
Epcoritamab'
crs
Grade 1 50 (32%)
Grade 2 25 (16%)
Grade 3 5 (3%)
+ CRS primarily occurred following first full dose
(cycle 1, day 15)
+ Median time to onset after first full dose: 20 h
+ Median time to resolution, day (range): 2 (1-27)
ICANS
+ Itoccurred in 10 (6.4%) patients, including 7
patients with grade 1, 2 patients with grade 2,
and one fatal event
1. ThieblemontC ot al. J Clin Oncol. 2023:41:2238-2247. 2. Dickinson MJ et al. N Engl J Mod. 2022:387-2220-2231
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Glofitamab?
one
Grade 1 48%
Grade 2 12%
Grade 3 3%
+ Primarily associated with the first 3 glofitamab
doses (median time to onset from the cycle 1, day
8 dose, 13.5 h (range, 6.0-52.0)
* Median duration, 30.5 hours (range, 0.5-317.0)
ICANS
* It occurred in 12 patients (8%), with events of
grade 3 or higher in 3%
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Epcoritamab'
crs
Grade 1 50 (32%)
Grade 2 25 (16%)
Grade 3 5 (3%)
+ CRS primarily occurred following first full dose
(cycle 1, day 15)
+ Median time to onset after first full dose: 20 h
+ Median time to resolution, day (range): 2 (1-27)
ICANS
+ Itoccurred in 10 (6.4%) patients, including 7
patients with grade 1, 2 patients with grade 2,
and one fatal event
1. ThieblemontC ot al. J Clin Oncol. 2023:41:2238-2247. 2. Dickinson MJ et al. N Engl J Mod. 2022:387-2220-2231
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Glofitamab?
one
Grade 1 48%
Grade 2 12%
Grade 3 3%
+ Primarily associated with the first 3 glofitamab
doses (median time to onset from the cycle 1, day
8 dose, 13.5 h (range, 6.0-52.0)
* Median duration, 30.5 hours (range, 0.5-317.0)
ICANS
* It occurred in 12 patients (8%), with events of
grade 3 or higher in 3%
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Toxicity Mitigation
(©) Monitoring guidelines
O Steroid prophylaxis
Staff training and preparation
(B) Antimicrobial prophylaxis
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(©) Monitoring guidelines
O Steroid prophylaxis
Staff training and preparation
(B) Antimicrobial prophylaxis
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CAR-T vs Bispecific
ht © 2000-2024, Peerview
ht © 2000-2024, Peerview
Y
Y
Y
SEN
Bispecifics
Long-term follow-up
required
Off the shelf
Community
administration
Need for longer
treatment
Lower CRS, ICANS
Ramp up for
administration
PeerView.com/KQE827
Bispecifics vs CAR-T
CAR-T
Y
Y
=
SSN
Curative, long-term
efficacy
Manufacturing
required
Exclusive to
tertiary/specialized
centers
Access, logistics
One time dose with
hospitalization
Higher CRS, ICANS
Need for bridging
therapy
PeerView.com
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Y
Y
SEN
Bispecifics
Long-term follow-up
required
Off the shelf
Community
administration
Need for longer
treatment
Lower CRS, ICANS
Ramp up for
administration
PeerView.com/KQE827
Bispecifics vs CAR-T
CAR-T
Y
Y
=
SSN
Curative, long-term
efficacy
Manufacturing
required
Exclusive to
tertiary/specialized
centers
Access, logistics
One time dose with
hospitalization
Higher CRS, ICANS
Need for bridging
therapy
PeerView.com
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CAR-T and Bispecific Efficacy and Toxicity
FITAMAB* EPCORE®
IA-1' TRANSCEND? JULIE
Product Axi-cel Liso-cel Tisa-cel Glofitamab Epcoritamab
Median F/U, mo 60 24 40.3 12.6 10.7
ORR, % 83 75 52 63.1 52
CR, % 54 53 40 40 39
PFS, mo 5.9 6.8 29 49 44
OS, mo 25.8 27.3 11.1 12 NR
CRS, % (all grade) 93 39 58 63 479
ICANS, % (all grade) 64 23 21 8 6.4
1. Noelapu ei a Blood. 2023:141:2307-2315, 2. Abramson Jot al. Blood. 2024:143:404-416. 3, Scustr $ e al. Lancot Oncol 202122:1409-1415, ñ
4. Dickinson MJ otal. N Engl J Med. 2022;387:2220-2231. 5. Thieblemont ei al. Cin Oncol. 2023:41:2238-2247. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
FITAMAB* EPCORE®
IA-1' TRANSCEND? JULIE
Product Axi-cel Liso-cel Tisa-cel Glofitamab Epcoritamab
Median F/U, mo 60 24 40.3 12.6 10.7
ORR, % 83 75 52 63.1 52
CR, % 54 53 40 40 39
PFS, mo 5.9 6.8 29 49 44
OS, mo 25.8 27.3 11.1 12 NR
CRS, % (all grade) 93 39 58 63 479
ICANS, % (all grade) 64 23 21 8 6.4
1. Noelapu ei a Blood. 2023:141:2307-2315, 2. Abramson Jot al. Blood. 2024:143:404-416. 3, Scustr $ e al. Lancot Oncol 202122:1409-1415, ñ
4. Dickinson MJ otal. N Engl J Med. 2022;387:2220-2231. 5. Thieblemont ei al. Cin Oncol. 2023:41:2238-2247. PeerView.com
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What Are Strategies for
Therapeutic Sequencing in
DLBCL?
Therapeutic Sequencing in
DLBCL?
Using Bispecifics After CAR-T
Is Well-Established Based on the Evidence to Date
Subgroup N
Glofitamab effective in Overall 155
patients exposed to prior
CAR-T (CR of 35%)!
Similarly, epcoritamab
shows efficacy in this
population; ORR of 54.1%
and CR of 34.4%?
in Tumor Size, %
Best Change From Baseline
Patients
1. Dickinson Metal. N Engl J Med, 2022:387:2220-2251. 2. Thieblemont C ot al. J Clin Oncol 2023:41:2238-2247. PeerView.com
Peerview.com/KQE827 Copyright O 2000-2024, Peerview
Is Well-Established Based on the Evidence to Date
Subgroup N
Glofitamab effective in Overall 155
patients exposed to prior
CAR-T (CR of 35%)!
Similarly, epcoritamab
shows efficacy in this
population; ORR of 54.1%
and CR of 34.4%?
in Tumor Size, %
Best Change From Baseline
Patients
1. Dickinson Metal. N Engl J Med, 2022:387:2220-2251. 2. Thieblemont C ot al. J Clin Oncol 2023:41:2238-2247. PeerView.com
Peerview.com/KQE827 Copyright O 2000-2024, Peerview
Sequencing With CAR-T After Bispecifics!
Retrospective analysis of 47 patients
with R/R LBCL!
+ Patients treated with CD19-targeted
CAR-T after a prior CD20/22 x CD3
bispecific
+ Robust responses regardless of
length of washout period
— 80% ORR for shorter and
longer washout
+ No evidence of intrinsic cross-
resistance between CAR-T cells
and bispecific
1. Crochet Gt al. Blood. 2024 006 2024024826,
PeerView.com/KQE827
OS Since CAR-T Infusion
‘Survival Probability
N___Eventn(%) _Consored, n (%) Median Survival (95% CD; mo
471782) 30638) ARENA)
0 y 3 E] E
OS Since CAR-T Administration, mo
Data suggest that CAR-T cell therapy remains effective
in patients with R/R LBCL after prior exposure to
bispecifics when the target antigen is different
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Retrospective analysis of 47 patients
with R/R LBCL!
+ Patients treated with CD19-targeted
CAR-T after a prior CD20/22 x CD3
bispecific
+ Robust responses regardless of
length of washout period
— 80% ORR for shorter and
longer washout
+ No evidence of intrinsic cross-
resistance between CAR-T cells
and bispecific
1. Crochet Gt al. Blood. 2024 006 2024024826,
PeerView.com/KQE827
OS Since CAR-T Infusion
‘Survival Probability
N___Eventn(%) _Consored, n (%) Median Survival (95% CD; mo
471782) 30638) ARENA)
0 y 3 E] E
OS Since CAR-T Administration, mo
Data suggest that CAR-T cell therapy remains effective
in patients with R/R LBCL after prior exposure to
bispecifics when the target antigen is different
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Preparing for Emerging
Bispecifics in DLBCL
Bispecifics in DLBCL
ELM-2 Design and Odronextamab Dosing
Key eligibility criteria
+ DLBCL per WHO 2016 classification
+ ECOGPS0or1
+ Refractory to or relapsed after 22 prior lines of therapy, including an anti-CD20 antibody and
an alkylator
Primary endpoint: ORR by ICR Odronextamab administration (IV, 21-day cycles)
Secondary endpokte, Cycle 1 (step up) Cycles 2-4 Cycle 5+ (maintenance)
+ ORR by local investigator 01/2, 8/9, 15/16 01,8, 15 Q2W > Q4Wif
+ CR, DOR, PFS, and OS durable CR (29 mo)
+ Safety and tolerability 0.7/4/20 mgt 160 mg 320 mg
+ Patient-reported outcomes
lo 4 Day 15
Key exploratory endpoint: MRD. pu er ceros sas
1. Ayyappan S etal, ASH 2023. Abstract 436. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Key eligibility criteria
+ DLBCL per WHO 2016 classification
+ ECOGPS0or1
+ Refractory to or relapsed after 22 prior lines of therapy, including an anti-CD20 antibody and
an alkylator
Primary endpoint: ORR by ICR Odronextamab administration (IV, 21-day cycles)
Secondary endpokte, Cycle 1 (step up) Cycles 2-4 Cycle 5+ (maintenance)
+ ORR by local investigator 01/2, 8/9, 15/16 01,8, 15 Q2W > Q4Wif
+ CR, DOR, PFS, and OS durable CR (29 mo)
+ Safety and tolerability 0.7/4/20 mgt 160 mg 320 mg
+ Patient-reported outcomes
lo 4 Day 15
Key exploratory endpoint: MRD. pu er ceros sas
1. Ayyappan S etal, ASH 2023. Abstract 436. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Probability
ELM-2: Efficacy Analysis (ICR)!
Median duration of follow-up for efficacy: 29.9 mo (95% Cl, 20.4-32.6)
N = 127: ORR 52.0%, CR 31.5%
DOR
10
08
Median DOR: 10.2 months
08 (95% CI 5.0-17.9)
04
0.27 12.month DOR: 48.1% (95% CI 35.1-59.9)
24-month DOR: 36.9% (95% CI 24 2-49.6)
Probability
DOCR
10
os
‘Median DOCR: 17.9 months.
(95% CI 10.2-NE)
08
04
02 | 12.month DOCR: 61.5% (95% C144.4-74.8)
24-month DOCR: 47.2% (85% C129.7-62)
o
0 3 6 9 12 15 18 21 24 27 30 33 36
Time From First Response, mo
ot
0 3 6 9 12 15 18 21 24 27 30 33 36
Time From First CR, mo
No.atRisk: 68 46 36 31 23 18 15 14 14 10 6 2 0 No.atRisk: 40 35 29 26 19 15 12 11 10 8 5 1 0
1.Ayyappan S et a. ASH 2023. Abstract 436. PeerView.com
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ELM-2: Efficacy Analysis (ICR)!
Median duration of follow-up for efficacy: 29.9 mo (95% Cl, 20.4-32.6)
N = 127: ORR 52.0%, CR 31.5%
DOR
10
08
Median DOR: 10.2 months
08 (95% CI 5.0-17.9)
04
0.27 12.month DOR: 48.1% (95% CI 35.1-59.9)
24-month DOR: 36.9% (95% CI 24 2-49.6)
Probability
DOCR
10
os
‘Median DOCR: 17.9 months.
(95% CI 10.2-NE)
08
04
02 | 12.month DOCR: 61.5% (95% C144.4-74.8)
24-month DOCR: 47.2% (85% C129.7-62)
o
0 3 6 9 12 15 18 21 24 27 30 33 36
Time From First Response, mo
ot
0 3 6 9 12 15 18 21 24 27 30 33 36
Time From First CR, mo
No.atRisk: 68 46 36 31 23 18 15 14 14 10 6 2 0 No.atRisk: 40 35 29 26 19 15 12 11 10 8 5 1 0
1.Ayyappan S et a. ASH 2023. Abstract 436. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
ELM-2: Patients With CR Achieved
Robust PFS and OS Outcomes!
PFS by Best Overall Respon:
OS by Best Overall Response
10 10
08 03
> : CR
g Median PFS: 20.4 mo 2 Median OS: NR (95% Cl, 17.2-NE)
306 (85% Cl, 127-NE) 30
2 a
Boa © 04 Median OS: 17 mo
Median PFS: 58 mo E (85% CI, 9.6-27.3)
o 0
Time From First Dose, mo
PO PN Time From First Dose, mo
ann man |
12-mo PFS, % (95% Cl) 67.2 (50.3-79.5) 25.2 (9.5-44.7) 12-mo OS, % =
= re
120 PFS, %(95%C1) 47.5 (20.9-62.1) 189 (54-388) 12:10 08, % (5%: BEAT 59503653)
Smresemo) ven meine pmmremo Pe" mama
1. Ayyappan S et al. ASH 2023. Abstract 436, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Robust PFS and OS Outcomes!
PFS by Best Overall Respon:
OS by Best Overall Response
10 10
08 03
> : CR
g Median PFS: 20.4 mo 2 Median OS: NR (95% Cl, 17.2-NE)
306 (85% Cl, 127-NE) 30
2 a
Boa © 04 Median OS: 17 mo
Median PFS: 58 mo E (85% CI, 9.6-27.3)
o 0
Time From First Dose, mo
PO PN Time From First Dose, mo
ann man |
12-mo PFS, % (95% Cl) 67.2 (50.3-79.5) 25.2 (9.5-44.7) 12-mo OS, % =
= re
120 PFS, %(95%C1) 47.5 (20.9-62.1) 189 (54-388) 12:10 08, % (5%: BEAT 59503653)
Smresemo) ven meine pmmremo Pe" mama
1. Ayyappan S et al. ASH 2023. Abstract 436, PeerView.com
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Odronextamab Is Associated With a Manageable
Safety Profile Consistent With Prior Reports!
Treatment
pd
TEAEs in 215% of Patients (N = 127)
Any TEAE TRAE
Any TEAE 126 (99.2) 111 (67.4) crs] 551 ms 55.1
Grade 23 TEAE 107 (84.3) 68 (53.5) ee =
Serious TEAE 82 (64.6) 62 (48.8) Neutropenia 307 (en 20.5
TEAE leading to interruption 92 (72.4) 67 (52.8) Diarrhea 2 29.4 Grade
TEAE leading to dose Sach es m2
Me 4(3.1) 4(3.1) Thrombocytopenia 16.9 lm 14.2
TEAE leading to Hypokalemia 18.9 mim 63 Mas
NEES 17 (13.4) 12(9.4) Bi: 181 ml 16.5
TEAE leading to death 20(15.7) 5 (3.9) covip-19
Nausea’
TEAEs leading to death: COVID-19, pneumonia, Pneumocystis
Jirovecii pneumonia, pseudomonal sepsis, pneumonia 100 80 60 40 20 0 20 40 60 80 100
cytomegaloviral + cytomegalovirus infection reactivation (n = 1 Patients, %
each)
1. Ayyappan S etal, ASH 2023. Abstract 436. PeerView.com
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Safety Profile Consistent With Prior Reports!
Treatment
pd
TEAEs in 215% of Patients (N = 127)
Any TEAE TRAE
Any TEAE 126 (99.2) 111 (67.4) crs] 551 ms 55.1
Grade 23 TEAE 107 (84.3) 68 (53.5) ee =
Serious TEAE 82 (64.6) 62 (48.8) Neutropenia 307 (en 20.5
TEAE leading to interruption 92 (72.4) 67 (52.8) Diarrhea 2 29.4 Grade
TEAE leading to dose Sach es m2
Me 4(3.1) 4(3.1) Thrombocytopenia 16.9 lm 14.2
TEAE leading to Hypokalemia 18.9 mim 63 Mas
NEES 17 (13.4) 12(9.4) Bi: 181 ml 16.5
TEAE leading to death 20(15.7) 5 (3.9) covip-19
Nausea’
TEAEs leading to death: COVID-19, pneumonia, Pneumocystis
Jirovecii pneumonia, pseudomonal sepsis, pneumonia 100 80 60 40 20 0 20 40 60 80 100
cytomegaloviral + cytomegalovirus infection reactivation (n = 1 Patients, %
each)
1. Ayyappan S etal, ASH 2023. Abstract 436. PeerView.com
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What Is the Efficacy of Odronextamab After CAR-T?
Odronextamab demonstrated encouraging antitumor activity in heavily pretreated
patients with R/R DLBCL who have progressed after CAR-T therapy!
— Expansion post-CAR-T cohort; only dedicated, prospective analysis to date
— ORR: 47.7%, CR: 29.5%
Reponses were durable with median DOR and median DOCR not reached
Outcome
All Patients (| )
Median DOR, mo (95% Cl) NR (2.3-NE)
Probability of maintaining response at 12 mo, % (95% CI) 61.6 (29.4-82.5)
Median DOCR, mo (95% Cl) NR (23-NE)
Probability of maintaining CR at 9 mo, % (95% Cl) 85.7 (33.4-97.9)
Median PFS and OS were longer with CR vs PR:
+ PFS NR vs 5.0 months; OS NR vs 7.7 months)
1. Combie J etal, ASH 2023. Abstract 461. PeerView.com
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Odronextamab demonstrated encouraging antitumor activity in heavily pretreated
patients with R/R DLBCL who have progressed after CAR-T therapy!
— Expansion post-CAR-T cohort; only dedicated, prospective analysis to date
— ORR: 47.7%, CR: 29.5%
Reponses were durable with median DOR and median DOCR not reached
Outcome
All Patients (| )
Median DOR, mo (95% Cl) NR (2.3-NE)
Probability of maintaining response at 12 mo, % (95% CI) 61.6 (29.4-82.5)
Median DOCR, mo (95% Cl) NR (23-NE)
Probability of maintaining CR at 9 mo, % (95% Cl) 85.7 (33.4-97.9)
Median PFS and OS were longer with CR vs PR:
+ PFS NR vs 5.0 months; OS NR vs 7.7 months)
1. Combie J etal, ASH 2023. Abstract 461. PeerView.com
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The OLYMPIA-4 Trial Will Further
Assess Odronextamab in R/R Aggressive NHL
Odronextamab
1 year
Patients with
Odronextamab
step-up regimen
Odronextamab
full dose
C4
Odronextamab
maintenanc
RIR aggressive
B-NHL®
* Includes the following subtypes: DLBCL, HGBL with and without MYC and BCL? or BCL6 translocations, PMBCL, THRBGL, and FL.
1. ps cinicalras gowstuoyNCT06230224.
PeerView.com/KQE827
Salvage therapy
$3 cycles
R, DHAP + R
or GDP + R)
Optional crossover
No optimal response
ASCT period 15 weeks
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Assess Odronextamab in R/R Aggressive NHL
Odronextamab
1 year
Patients with
Odronextamab
step-up regimen
Odronextamab
full dose
C4
Odronextamab
maintenanc
RIR aggressive
B-NHL®
* Includes the following subtypes: DLBCL, HGBL with and without MYC and BCL? or BCL6 translocations, PMBCL, THRBGL, and FL.
1. ps cinicalras gowstuoyNCT06230224.
PeerView.com/KQE827
Salvage therapy
$3 cycles
R, DHAP + R
or GDP + R)
Optional crossover
No optimal response
ASCT period 15 weeks
PeerView.com
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Are Combinations With Bispecifics on the Horizon?
Rationale for combining mosunetuzumab and polatuzumab vedotin; shown to be active in
R/R DLBCL'
Mosunetuzumab is a CD20XCD3 bispecific antibody that Polatuzumab vedotin is an antibody drug conjugate that
‘engages and redirects T cells to eliminate malignant B colis targets CD79 to deliver a microtubule-disrupting agent,
MMAE, directly to B cells*
ADC binds
Lo receptor
ox, Y du © ADc-receptor
complex is
4 > internalized
> coll . i
-
.
Moenia Apoptosis
(cell death)
Microtubule
disruption
* Glofitamab-pola has also shown efficacy in this setting?
1. Budde LE et al Nat Med, 2024:30229-230.2. Hutchings Meta. ASH 2023, Abstract 4460
PeerView.com
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Rationale for combining mosunetuzumab and polatuzumab vedotin; shown to be active in
R/R DLBCL'
Mosunetuzumab is a CD20XCD3 bispecific antibody that Polatuzumab vedotin is an antibody drug conjugate that
‘engages and redirects T cells to eliminate malignant B colis targets CD79 to deliver a microtubule-disrupting agent,
MMAE, directly to B cells*
ADC binds
Lo receptor
ox, Y du © ADc-receptor
complex is
4 > internalized
> coll . i
-
.
Moenia Apoptosis
(cell death)
Microtubule
disruption
* Glofitamab-pola has also shown efficacy in this setting?
1. Budde LE et al Nat Med, 2024:30229-230.2. Hutchings Meta. ASH 2023, Abstract 4460
PeerView.com
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(2) Workshop: Revisiting Our Patient With DLBCL
65-year-old patient with DLBCL NOS treated with R-CHOP and achieves complete
response (CR) confirmed by PET-CT (PS of 1).
+ 6 months post treatment, he shows signs of relapse and is referred for CAR-T and
achieves a remission; after 6 months, he is found to have progression based on
imaging. Biopsy proven to be DLBCL NOS
Summary Thoughts
Yes, there is life after CAR-T: bispecifics are effective options in patients progressing on cellular therapy
“Off-the-shelf” therapy with a favorable safety profile
Multiple bispecifics included in the NCCN guidelines could be considered for this patient; emerging
CD20 x CD3s may have a future role
Combination therapy may also be emerging as an option
As these agents move upfront, sequencing will remain an area of interest
PeerView.com
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65-year-old patient with DLBCL NOS treated with R-CHOP and achieves complete
response (CR) confirmed by PET-CT (PS of 1).
+ 6 months post treatment, he shows signs of relapse and is referred for CAR-T and
achieves a remission; after 6 months, he is found to have progression based on
imaging. Biopsy proven to be DLBCL NOS
Summary Thoughts
Yes, there is life after CAR-T: bispecifics are effective options in patients progressing on cellular therapy
“Off-the-shelf” therapy with a favorable safety profile
Multiple bispecifics included in the NCCN guidelines could be considered for this patient; emerging
CD20 x CD3s may have a future role
Combination therapy may also be emerging as an option
As these agents move upfront, sequencing will remain an area of interest
PeerView.com
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Next Steps in Lymphoma—
Bispecifics on the Move
Follicular Lymphoma
Jennifer Crombie, MD
Assistant Professor of Medicine, Harvard Medical School
Dana-Farber Cancer Institute
Boston, Massachusetts
Copyright © 2000-2024, PeerView
Bispecifics on the Move
Follicular Lymphoma
Jennifer Crombie, MD
Assistant Professor of Medicine, Harvard Medical School
Dana-Farber Cancer Institute
Boston, Massachusetts
Copyright © 2000-2024, PeerView
(2) Workshop: A Patient With Follicular Lymphoma
Diagnosed with FL, Treated with BR x 6 Recurrent disease Treated with R2 with CR,
symptomatic with with a CR 18 months later, relapsed 12 months later
bulky abdominal biopsy showed FL with symptomatic
disease lymphadenopathy
* Patient does not live near a CAR-T center and prefers not to travel at this time
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Diagnosed with FL, Treated with BR x 6 Recurrent disease Treated with R2 with CR,
symptomatic with with a CR 18 months later, relapsed 12 months later
bulky abdominal biopsy showed FL with symptomatic
disease lymphadenopathy
* Patient does not live near a CAR-T center and prefers not to travel at this time
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(2) Workshop: A Patient With Follicular Lymphoma
A 73-year-old woman with R/R FL previously treated with 1L CIT and evidence of POD24;
subsequently the patient receives R2 and responds but experiences neutropenia, managed with
GCSF; subsequent relapse, PS is now 2 and CAR-T has not been planned.
Points to consider
+ Prognostic considerations
+ What are treatment options?
+ If bispecifics are used: what are the dosing, safety, and administration
considerations?
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A 73-year-old woman with R/R FL previously treated with 1L CIT and evidence of POD24;
subsequently the patient receives R2 and responds but experiences neutropenia, managed with
GCSF; subsequent relapse, PS is now 2 and CAR-T has not been planned.
Points to consider
+ Prognostic considerations
+ What are treatment options?
+ If bispecifics are used: what are the dosing, safety, and administration
considerations?
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Analysis of >5,000 Patients With FL Confirms POD24
as an Important Indicator of Subsequent Survival!
24-Month Landmark OS Based on Status of Disease Progression
Within 24 Months in Patients With FL
100
90
20
70
x 60
we 50
S 4 EventsTotal; Median (95% C1) HR:(25% Cl) Time Point KM Est (95% Cl)
3y soon
20 | — moro mamma monos BY 2500020
20) — »o senos menor omas 3 aos
= on Sy some
10) — mm masse) 37 poo»
0
2 o” 5 8 T4 à
No. at Risk Time, y
Nero 3300 a a du a une 1% tam
E
noue 4 ee SU 22% 206 40 120 70
+ Adjstod for genderstatlied by PS, FLIP
1. Casulo C etal. Blood. 2022:139:1684-1693, PeerView.com
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as an Important Indicator of Subsequent Survival!
24-Month Landmark OS Based on Status of Disease Progression
Within 24 Months in Patients With FL
100
90
20
70
x 60
we 50
S 4 EventsTotal; Median (95% C1) HR:(25% Cl) Time Point KM Est (95% Cl)
3y soon
20 | — moro mamma monos BY 2500020
20) — »o senos menor omas 3 aos
= on Sy some
10) — mm masse) 37 poo»
0
2 o” 5 8 T4 à
No. at Risk Time, y
Nero 3300 a a du a une 1% tam
E
noue 4 ee SU 22% 206 40 120 70
+ Adjstod for genderstatlied by PS, FLIP
1. Casulo C etal. Blood. 2022:139:1684-1693, PeerView.com
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Bispecific Antibodies Are Now Options for
Sequential FL Management in Current Guidelines!
Suggested Treatment Regimens
An FDA-Approved Biosimilar Is an Appropriate Substitute for Rituximab
Third-Line and Subsequent Therapy
Subsequent Systemic Therapy Options Include Second-line Therapy Regimens That Were Not Previously Given
Preferred regimens
in alphabetical order)
+ T-cell engager therapy
o Bispecific antibody therapy
> > Epcoritamab-bysp
> Mosunetuzumab-axgb
> CAR T-cell therapy
(preferred if not previously given) (in alphabetical order)
> Axicabtagene ciloleucel (CD19-directed)
> Lisocabtagene maraleucel (CD19-directed)
> Tisagenlecleucel (CD19-directed)
her recommen men:
+ EZH2 inhibitor
o Tazemetostat (irrespective of EZH2 mutation status)
+ BTK inhibitor
Zanubrutinib + obinutuzumab
+ Mosunetuzumab?
+ Epcoritamab added, though awaiting FDA approval
1. NCCN cincal Practico Gudeines in Oncology. -Cel Lymphomas. Version 22024. htps:wnw.neen.or/proessionlphysican_olspa-col pal. ew.
2. Budde LE etal. Lancet Oncol 2022.23 1055-1085, es eee ee PeerView.com
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Sequential FL Management in Current Guidelines!
Suggested Treatment Regimens
An FDA-Approved Biosimilar Is an Appropriate Substitute for Rituximab
Third-Line and Subsequent Therapy
Subsequent Systemic Therapy Options Include Second-line Therapy Regimens That Were Not Previously Given
Preferred regimens
in alphabetical order)
+ T-cell engager therapy
o Bispecific antibody therapy
> > Epcoritamab-bysp
> Mosunetuzumab-axgb
> CAR T-cell therapy
(preferred if not previously given) (in alphabetical order)
> Axicabtagene ciloleucel (CD19-directed)
> Lisocabtagene maraleucel (CD19-directed)
> Tisagenlecleucel (CD19-directed)
her recommen men:
+ EZH2 inhibitor
o Tazemetostat (irrespective of EZH2 mutation status)
+ BTK inhibitor
Zanubrutinib + obinutuzumab
+ Mosunetuzumab?
+ Epcoritamab added, though awaiting FDA approval
1. NCCN cincal Practico Gudeines in Oncology. -Cel Lymphomas. Version 22024. htps:wnw.neen.or/proessionlphysican_olspa-col pal. ew.
2. Budde LE etal. Lancet Oncol 2022.23 1055-1085, es eee ee PeerView.com
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Mosunetuzumab Treatment Schedule
You will receive an infusion on day 1 of
Day2 Day3 Day4 Day5 Day6 Day? wea Sada
The doses you will receive on day 1 of
weeks 1 and 2 will be smaller than the
‘ones you will receive throughout the rest of
your treatment. This is called a step-up
dosing schedule
If your dose of mosunetuzumab is delayed
for any reason, you may need to repeat the
step-up dosing schedule
Starting on day 1 of week 7, you will receive
an infusion every 3 weeks (21 days)
Treatment will continue for
-6 months or 1 year, depending on
response after 8 cycles
Download the
Practice Aid!
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Mosunetuzumab Treatment Schedule
You will receive an infusion on day 1 of
Day2 Day3 Day4 Day5 Day6 Day? wea Sada
The doses you will receive on day 1 of
weeks 1 and 2 will be smaller than the
‘ones you will receive throughout the rest of
your treatment. This is called a step-up
dosing schedule
If your dose of mosunetuzumab is delayed
for any reason, you may need to repeat the
step-up dosing schedule
Starting on day 1 of week 7, you will receive
an infusion every 3 weeks (21 days)
Treatment will continue for
-6 months or 1 year, depending on
response after 8 cycles
Download the
Practice Aid!
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Mosunetuzumab Active in R/R FL!
Progression-Free Survival
Median 17.9 (95% Cl, 10.1-NR)
ape Time, mo
AA ee
80% objective response
60% of patients with CR
Median PFS of 17.9 months
57% of patients maintaining
18 months
OR for at least
Ago, y (range) 60 (53-67) Previous lines of therapy 3024)
en B Hay
es se M a
mei man ae
pans som su
= oo Man EB
= a
oe ty le
ae Mer
= EN non
3 ió 53 (69) Immunomodulatory drugs 134)
1 37 (41) F5 A)
ee a
E a
: o ae
le Sat] a rien
iy aes IE A
TE er Os um
rt 3134) r= saad
Pa: Eee]
o 33) i)
i 28
E ta
1. Budde LE etal. Lancet Oncol. 2022:28:1085-1066.
PeerView.com/KQE827
Median DOR of 22.8 months
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Progression-Free Survival
Median 17.9 (95% Cl, 10.1-NR)
ape Time, mo
AA ee
80% objective response
60% of patients with CR
Median PFS of 17.9 months
57% of patients maintaining
18 months
OR for at least
Ago, y (range) 60 (53-67) Previous lines of therapy 3024)
en B Hay
es se M a
mei man ae
pans som su
= oo Man EB
= a
oe ty le
ae Mer
= EN non
3 ió 53 (69) Immunomodulatory drugs 134)
1 37 (41) F5 A)
ee a
E a
: o ae
le Sat] a rien
iy aes IE A
TE er Os um
rt 3134) r= saad
Pa: Eee]
o 33) i)
i 28
E ta
1. Budde LE etal. Lancet Oncol. 2022:28:1085-1066.
PeerView.com/KQE827
Median DOR of 22.8 months
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Safety of Mosunetuzumab’
CRS (44%): G1: 26%, G2: 17%, G3: 1%, G4: 1%
Most commonly occurs
— C1D1: 23% (5 h after dosing)
— C1D15: 36% (25 h after dosing
Cycle and Day of Treatment M Er mg
Day 1 1 x
Cycle 1 Day 8 2
Day 15 60 A
Cycle 2 Day 1 60
Cycles 3+ Day 1 30
1. Budde LE ot al Lancet Oncol. 2022:28:1085-1068.
PeerView.com/KQE827
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CRS (44%): G1: 26%, G2: 17%, G3: 1%, G4: 1%
Most commonly occurs
— C1D1: 23% (5 h after dosing)
— C1D15: 36% (25 h after dosing
Cycle and Day of Treatment M Er mg
Day 1 1 x
Cycle 1 Day 8 2
Day 15 60 A
Cycle 2 Day 1 60
Cycles 3+ Day 1 30
1. Budde LE ot al Lancet Oncol. 2022:28:1085-1068.
PeerView.com/KQE827
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EPCORE-NHL-1: Epcoritamab Is Highly
Active in the R/R FL Cohort’
Demographics, n (%) Efficacy Results: ORRs and CR Rates Were High
— Regardless of Subgroup
Median age, y (range) ee MEN) 100 =PR «CR 97
(ang)
Median time tom end ot
Men 70,62) latino lero o et 52 (1-105) o nn
Gone mo range)
edn na om odo *
ee sc E
2
é
first dose, mo (range)
Median prior lines of
therapy, n (range) 329
2 8169) a
= 106
o
z a | poo 442) range Nee ae Macey ae ea
ES 760) ote egy Tose” TE
Double refractory.’ 90(70) ud id j,
= ee) Including in treatment-refractory and POD24 settings
mocralbuln: m :
Refractory to lat prior sn * Median PFS, 15.4 months
on 7262 | |sssenic mao,
+ Median OS, NR
+ Ann Arbor sage was lil in 19 paint. FLIP was 0-1 in 17 patients, unknown for 1 paint and not applcabe fr 1 patent. FLIP was riot fet dose on study.
“Botn-2 macrogbuln was normal in 46 patents and missing for 4 pants. Progression within 2 y ol ıntatng 1L chemoimranotherapy
Rotator no response o elapse wa 6 mo alr therapy.‘ Dodble refactor retractor to both ant-C020 and an aiii agent ge
1: Linton KM et a. ASH 2029. Abstract 1855. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Active in the R/R FL Cohort’
Demographics, n (%) Efficacy Results: ORRs and CR Rates Were High
— Regardless of Subgroup
Median age, y (range) ee MEN) 100 =PR «CR 97
(ang)
Median time tom end ot
Men 70,62) latino lero o et 52 (1-105) o nn
Gone mo range)
edn na om odo *
ee sc E
2
é
first dose, mo (range)
Median prior lines of
therapy, n (range) 329
2 8169) a
= 106
o
z a | poo 442) range Nee ae Macey ae ea
ES 760) ote egy Tose” TE
Double refractory.’ 90(70) ud id j,
= ee) Including in treatment-refractory and POD24 settings
mocralbuln: m :
Refractory to lat prior sn * Median PFS, 15.4 months
on 7262 | |sssenic mao,
+ Median OS, NR
+ Ann Arbor sage was lil in 19 paint. FLIP was 0-1 in 17 patients, unknown for 1 paint and not applcabe fr 1 patent. FLIP was riot fet dose on study.
“Botn-2 macrogbuln was normal in 46 patents and missing for 4 pants. Progression within 2 y ol ıntatng 1L chemoimranotherapy
Rotator no response o elapse wa 6 mo alr therapy.‘ Dodble refactor retractor to both ant-C020 and an aiii agent ge
1: Linton KM et a. ASH 2029. Abstract 1855. PeerView.com
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Safety of Epcoritamab in FL!
‘Step-Up Dosing
do
Treatment until PD or unace
IR FL grade 1-3A expansion cohort
Dose Expansion C1 Optimization
> RP2D 48 mg
ptable toxicity
Epcoritamab CRS prophylaxis with
dexamethasone 15 mg
N=12
SC injections in minutes
SUD 3: 3 me
©1022
First full dose: 48 mg
D15
9
Ds
SUD 2:08 mg
oy Zu cıDı Recommendations for
ECO D 1:06 mg adequate hydration
En EE + Hospitalization not mandated in his setting
C1 Optimization Reduced Risk and Severity of CRS
Pivotal Cohort C1 Optimization
(n= 128) Cohort {n = 50)
CRS,n (%) 85 (66) 24 (48)
Grade 1 51 (40) 20 40)
Grade 2 32(25) 40)
Grade 3 2@) o
Treated with toclizumab, nin (%) 21785 (96) 6724 (25)
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1. Linton KM etal, ASH 2023, Abstract 1655,
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‘Step-Up Dosing
do
Treatment until PD or unace
IR FL grade 1-3A expansion cohort
Dose Expansion C1 Optimization
> RP2D 48 mg
ptable toxicity
Epcoritamab CRS prophylaxis with
dexamethasone 15 mg
N=12
SC injections in minutes
SUD 3: 3 me
©1022
First full dose: 48 mg
D15
9
Ds
SUD 2:08 mg
oy Zu cıDı Recommendations for
ECO D 1:06 mg adequate hydration
En EE + Hospitalization not mandated in his setting
C1 Optimization Reduced Risk and Severity of CRS
Pivotal Cohort C1 Optimization
(n= 128) Cohort {n = 50)
CRS,n (%) 85 (66) 24 (48)
Grade 1 51 (40) 20 40)
Grade 2 32(25) 40)
Grade 3 2@) o
Treated with toclizumab, nin (%) 21785 (96) 6724 (25)
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1. Linton KM etal, ASH 2023, Abstract 1655,
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Other Emerging Bispecifics: Odronextamab in R/R FL!
ELM-2 FL Cohort Odronextamab Administration (IV, 21-Day Cycles)
49% of patients were POD24
Cycle 5+
Cycle 1 (step-up) Cycle 2-4 (maintenance)
D: 1/2, 8/9, 15/16 D:1,8,and15 Q2W > Q4Wif
Key Eligibility Criteria durable CR (29 mo)
FL grade 1-3
Kessler 0.7/4/20 mg 80 mg 160 mg >
Refractory to or relapsed after 22
prior lines of therapy, including an 4
anti-CD20 antibody and an
alkylator Cycle 4 day 15
Pi SE ORRINICR First post-baseline response
Seconded) endpoints: ORR by local Modified step-up dosing to mitigate CRS
investigator; CR, DOR, PFS, and OS; safety
and tolerability; patient-reported outcomes
Key exploratory endpoint: MRD
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1. Vitasboas JC ot al ASH 2023. Abstract 3041
Copyright © 2000-2024, PeerView
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ELM-2 FL Cohort Odronextamab Administration (IV, 21-Day Cycles)
49% of patients were POD24
Cycle 5+
Cycle 1 (step-up) Cycle 2-4 (maintenance)
D: 1/2, 8/9, 15/16 D:1,8,and15 Q2W > Q4Wif
Key Eligibility Criteria durable CR (29 mo)
FL grade 1-3
Kessler 0.7/4/20 mg 80 mg 160 mg >
Refractory to or relapsed after 22
prior lines of therapy, including an 4
anti-CD20 antibody and an
alkylator Cycle 4 day 15
Pi SE ORRINICR First post-baseline response
Seconded) endpoints: ORR by local Modified step-up dosing to mitigate CRS
investigator; CR, DOR, PFS, and OS; safety
and tolerability; patient-reported outcomes
Key exploratory endpoint: MRD
PeerView.com
1. Vitasboas JC ot al ASH 2023. Abstract 3041
Copyright © 2000-2024, PeerView
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Other Emerging Bispecifics: Odronextamab in R/R FL!
28
61 (22-84)
94
53.1
517
266
08
16
94
‘Ann Arbor stage IV 852
FLIPI risk score
0.1 164
35 578
Prior RE 133
Prior ASCT, %. 305
Refractory to last line of therapy ns
Refractory to anti-CD20 antibody 742
Double refractory to alkylatorianti-CD20 ad
1. Vilasboas JC et al. ASH 2023. Abstract 3041. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
28
61 (22-84)
94
53.1
517
266
08
16
94
‘Ann Arbor stage IV 852
FLIPI risk score
0.1 164
35 578
Prior RE 133
Prior ASCT, %. 305
Refractory to last line of therapy ns
Refractory to anti-CD20 antibody 742
Double refractory to alkylatorianti-CD20 ad
1. Vilasboas JC et al. ASH 2023. Abstract 3041. PeerView.com
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+ ORR: 80.5%
+ CR: 73.5%
ELM-2: Odronextamab Is Effective in
R/R FL, With Durable Responses!
PFS
| Patients switched from 80 mg to 160 mg
Probability
e o e
2382
8
Median PFS: 20.7 mo (95% Cl, 17.2-27.5)
0 3 6 9 12151821 24 27 30 33 36 39 42
ime From First Dose, mo
8 109 89 76 68 49 36 28 24 21:14:12 5 2 0
12m0 PFS, % (95% CI) 65.9 56.5-73.7)
12:m0 PFS, % (95% CI) 45 (937.556)
1. Vitasboas JC ot al. ASH 2023. Abstract 3041
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PFS by Response (CR vs PR)
Patents switched from 80 mg to 160 mg
10
08
06 Median PFS: 27.5 mo
3 (95% Cl, 20.2-NE)
Bos
E
02 Median PFS: 8 mo
— (95% Cl, 4.4-17.2)
0
0 3 6 9 1215 18 21 24 27 30 33 36 3942
Time From First Dose, mo
No, at Risk
2110000
12-m0 PFS, % (95% CI) 78:8(687-859) 42.9 (9.8-73.4)
120 PFS, % (95% Cl) $5.8 (61.7-67.8)_NE(NE-NE)
R 94 93 81 70 63 45 34 26 23 21 14 12 5 2 0
9 3 000
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+ CR: 73.5%
ELM-2: Odronextamab Is Effective in
R/R FL, With Durable Responses!
PFS
| Patients switched from 80 mg to 160 mg
Probability
e o e
2382
8
Median PFS: 20.7 mo (95% Cl, 17.2-27.5)
0 3 6 9 12151821 24 27 30 33 36 39 42
ime From First Dose, mo
8 109 89 76 68 49 36 28 24 21:14:12 5 2 0
12m0 PFS, % (95% CI) 65.9 56.5-73.7)
12:m0 PFS, % (95% CI) 45 (937.556)
1. Vitasboas JC ot al. ASH 2023. Abstract 3041
PeerView.com/KQE827
PFS by Response (CR vs PR)
Patents switched from 80 mg to 160 mg
10
08
06 Median PFS: 27.5 mo
3 (95% Cl, 20.2-NE)
Bos
E
02 Median PFS: 8 mo
— (95% Cl, 4.4-17.2)
0
0 3 6 9 1215 18 21 24 27 30 33 36 3942
Time From First Dose, mo
No, at Risk
2110000
12-m0 PFS, % (95% CI) 78:8(687-859) 42.9 (9.8-73.4)
120 PFS, % (95% Cl) $5.8 (61.7-67.8)_NE(NE-NE)
R 94 93 81 70 63 45 34 26 23 21 14 12 5 2 0
9 3 000
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Manageable Safety Profile With Odronextamab in FL
y summary!
CRS was mostly grade 1/2 CRS
Neutropenia
* One low-grade ICANS event with Pyrexia
0.7/4/20 mg cycle 1 step-up ey
+ Any-grade infection TEAEs were an
reported in 80% of patients
Diarrhea
* >1/3 with COVID-19 Thrombocytopenia
— Reflective of a study conducted "Poklemia
during the pandemic in a patient Nausea
population with increased Rast
underlying risk for infections Fatigue |
Any TEAE Treatment-Related TEAE
je 55,3
47.7 | 39.5
259 mm 254
33.6 mm 20 3
313 ln 39 rods
205 | mE 26 9 m2
273 | 9.4. MR
242 nl 172
219 im 75
105 lm 10.2
166 lm 117
18 lm 125
100 80 60 40 20 0 20 40 60 80 100
Patients, % Patients, %
Patient-reported HRQoL: results were favorable during odronextamab treatment until disease
progression, with no detriments on patient-reported symptoms, functioning, and overall QoL?
1. Vitasboas JC et al. ASH 2023. Abstract 3041. 2, Tessouln B et al. ASH 2023 Abstract 669.
PeerView.com/KQE827
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y summary!
CRS was mostly grade 1/2 CRS
Neutropenia
* One low-grade ICANS event with Pyrexia
0.7/4/20 mg cycle 1 step-up ey
+ Any-grade infection TEAEs were an
reported in 80% of patients
Diarrhea
* >1/3 with COVID-19 Thrombocytopenia
— Reflective of a study conducted "Poklemia
during the pandemic in a patient Nausea
population with increased Rast
underlying risk for infections Fatigue |
Any TEAE Treatment-Related TEAE
je 55,3
47.7 | 39.5
259 mm 254
33.6 mm 20 3
313 ln 39 rods
205 | mE 26 9 m2
273 | 9.4. MR
242 nl 172
219 im 75
105 lm 10.2
166 lm 117
18 lm 125
100 80 60 40 20 0 20 40 60 80 100
Patients, % Patients, %
Patient-reported HRQoL: results were favorable during odronextamab treatment until disease
progression, with no detriments on patient-reported symptoms, functioning, and overall QoL?
1. Vitasboas JC et al. ASH 2023. Abstract 3041. 2, Tessouln B et al. ASH 2023 Abstract 669.
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How Do Bispecifics
Compare to CAR-T?
ht © 2000-2024, Peerview
Compare to CAR-T?
ht © 2000-2024, Peerview
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Comparison of CAR-T and Bispecifics
Odron®
ORR, % 94 97 86.2 80 82 80.5
. NR (24,
Median PFS, mo 402 NR 57.4%) 17.9 15.4 20.7
CRS, % 78 58 48.5 44 66 56.3
Grade 3+ CRS, % 6 1 0 2 2: 1:7
Grade 3+ NT, % 15 2 3 0 0 17
1. Jacobson C tal. Lancet Oncol 20222391109. 2. Morschhauser Ft al ICM 2023, 3. Fowler Nat al. Nat Mad. 202228.325-332 4. Budde LE etal. Lancet mn
‘Oncol. 2022:23-1055-1085. 5. Linton KM et al. ASH 2023. Abstract 1655. 6. Vilasboas JC et al. ASH 2023. Abstract 3041 PeerView.com
Copyright © 2000-2024, PeerView
Comparison of CAR-T and Bispecifics
Odron®
ORR, % 94 97 86.2 80 82 80.5
. NR (24,
Median PFS, mo 402 NR 57.4%) 17.9 15.4 20.7
CRS, % 78 58 48.5 44 66 56.3
Grade 3+ CRS, % 6 1 0 2 2: 1:7
Grade 3+ NT, % 15 2 3 0 0 17
1. Jacobson C tal. Lancet Oncol 20222391109. 2. Morschhauser Ft al ICM 2023, 3. Fowler Nat al. Nat Mad. 202228.325-332 4. Budde LE etal. Lancet mn
‘Oncol. 2022:23-1055-1085. 5. Linton KM et al. ASH 2023. Abstract 1655. 6. Vilasboas JC et al. ASH 2023. Abstract 3041 PeerView.com
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How Can We Use These
Agents Safely in the
Community?
Agents Safely in the
Community?
Practical Principles for Addressing
Bispecific Antibody Toxicity!
CRS/Neurotoxicity Patient Assessment
Patient Patient Drug Self-Monitoring
Assessment With Negative
Selection Education Administration (fOutpatient) Heer Does Negative
Neurotoxicity
Continue
+ therapy and
monitoring as
+ CRS risk
‘assessment Patient and caregiver Patient receives Patientorcaregiver Patient is assessed
+ Tumor burden ‘educated on bispecificin self-monitors vitals at DY HCP at 24 and
* Comoros. CR eurarciy | npaentcuipaen home dung step-up 4 Pours, and as
+ Social support risk and monitoring setting dosing Later
‘Assessment is positive for
‘Subsequent CRS and/or neurotoxicity
‘monitoring repeated
as above
CRS management Neurotoxicity management
1. Crombie Jet al. Blood. 2024:143:1565-1575. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Bispecific Antibody Toxicity!
CRS/Neurotoxicity Patient Assessment
Patient Patient Drug Self-Monitoring
Assessment With Negative
Selection Education Administration (fOutpatient) Heer Does Negative
Neurotoxicity
Continue
+ therapy and
monitoring as
+ CRS risk
‘assessment Patient and caregiver Patient receives Patientorcaregiver Patient is assessed
+ Tumor burden ‘educated on bispecificin self-monitors vitals at DY HCP at 24 and
* Comoros. CR eurarciy | npaentcuipaen home dung step-up 4 Pours, and as
+ Social support risk and monitoring setting dosing Later
‘Assessment is positive for
‘Subsequent CRS and/or neurotoxicity
‘monitoring repeated
as above
CRS management Neurotoxicity management
1. Crombie Jet al. Blood. 2024:143:1565-1575. PeerView.com
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Patient Information Sheets Can Help Prepare for TEAEs!
Patent name, ES
Diagnosis: Curent treatment:
“Treatment stan dato: My highest risk o side efocs ison (date
Treatment team
Contactintormaton:
RS symptoms o monitor fo
“Temperature 1004 F or greater
+ Pulse oxygen 590% or>5 change from baseline
+ Decrease in SBP >10 mtg from baseline andlor SBP
So mm
+ increased hear rato >110 0r>20 bpm trom baseline who
atrest
"Neurotoxicity symptoms to monitor for
Confusion
Diticuty wih speech
Diticuty staying awake
Seizures
What do | montor at home?
+ Temperature
+ Blood pressure
+ Hoar rate
+ Onygen leves
How often do 1 monitor?
Wien do cal my doctors office?
+ "Any symptom of CRS or change in thinking or speech
Wen should go straight to the ER?
‘What number should cal?
+ During office hours:
© Aller ofiee hours:
1. Crombie J eta, Blood. 2024;143:1865-1575
PeerView.com/KQE827
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Patent name, ES
Diagnosis: Curent treatment:
“Treatment stan dato: My highest risk o side efocs ison (date
Treatment team
Contactintormaton:
RS symptoms o monitor fo
“Temperature 1004 F or greater
+ Pulse oxygen 590% or>5 change from baseline
+ Decrease in SBP >10 mtg from baseline andlor SBP
So mm
+ increased hear rato >110 0r>20 bpm trom baseline who
atrest
"Neurotoxicity symptoms to monitor for
Confusion
Diticuty wih speech
Diticuty staying awake
Seizures
What do | montor at home?
+ Temperature
+ Blood pressure
+ Hoar rate
+ Onygen leves
How often do 1 monitor?
Wien do cal my doctors office?
+ "Any symptom of CRS or change in thinking or speech
Wen should go straight to the ER?
‘What number should cal?
+ During office hours:
© Aller ofiee hours:
1. Crombie J eta, Blood. 2024;143:1865-1575
PeerView.com/KQE827
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Pretreatment Planning With Bispec
Assemble/ .
connect
appropriate
healthcare
teams and
colleagues
Provide .
guidance to
patients,
caregivers, and
family
1. Crombie J ta, Blood. 2024;143:1865-1575
PeerView.com/KQE827
Steps for pretreatment planning
- Patient assessment
- Identify nearby hospital with ICU and tocilizumab
- Identify care team comfortable with bispecific therapy/CRS
- Educate emergency room staff
Patient and caregiver
- Education
- Ensure ability to measure vitals (temperature)
- Carry wallet card
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Assemble/ .
connect
appropriate
healthcare
teams and
colleagues
Provide .
guidance to
patients,
caregivers, and
family
1. Crombie J ta, Blood. 2024;143:1865-1575
PeerView.com/KQE827
Steps for pretreatment planning
- Patient assessment
- Identify nearby hospital with ICU and tocilizumab
- Identify care team comfortable with bispecific therapy/CRS
- Educate emergency room staff
Patient and caregiver
- Education
- Ensure ability to measure vitals (temperature)
- Carry wallet card
PeerView.com
Copyright © 2000-2024, PeerView
Principles of CRS Management With Bispecifics in NHL!
Grade 1
Home Home versus outpatient/ED evaluation
+ Tylenol + If recurrent fever, consider
dexamethasone 10 mg once
+ Consider earlier administration of steroids
and immediate in-person evaluation for
patients with multiple disease risk factors
or comorbidities
+ Consider daily dexamethasone with
persistent symptoms
+ Oral hydration
+ Monitor temperature (and other vitals if able)
every 1-2 hours
Additional management
+ Tocilizumab with protracted fever (e.g. >48 hours despite corticosteroids)
+ Early tocilizumab after trial of dexamethasone should be considered in patients with multiple
medical risk factors
1. Crombie Jet al. Blood. 2024:143:1565-1575. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Grade 1
Home Home versus outpatient/ED evaluation
+ Tylenol + If recurrent fever, consider
dexamethasone 10 mg once
+ Consider earlier administration of steroids
and immediate in-person evaluation for
patients with multiple disease risk factors
or comorbidities
+ Consider daily dexamethasone with
persistent symptoms
+ Oral hydration
+ Monitor temperature (and other vitals if able)
every 1-2 hours
Additional management
+ Tocilizumab with protracted fever (e.g. >48 hours despite corticosteroids)
+ Early tocilizumab after trial of dexamethasone should be considered in patients with multiple
medical risk factors
1. Crombie Jet al. Blood. 2024:143:1565-1575. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Principles of CRS Management With Bispecifics in NHL!
Grade 2
+ Evaluation in-person
+ Recommend inpatient management for most cases of Grade 2 CRS unless qualified
outpatient day hospital/infusion center and no hypoxia
+ Tylenol
+ Dexamethasone 10 mg every 12 hours
+ IVF/O2
+ Administer tocilizumab if symptoms persist despite IV fluids and dexamethasone
(approximately 4-6 hours after dosing) or if clinically unstable. Consider alternative agent
(e.g. anakinra or siltuximab) if persistent symptoms despite maximal dosing
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Grade 2
+ Evaluation in-person
+ Recommend inpatient management for most cases of Grade 2 CRS unless qualified
outpatient day hospital/infusion center and no hypoxia
+ Tylenol
+ Dexamethasone 10 mg every 12 hours
+ IVF/O2
+ Administer tocilizumab if symptoms persist despite IV fluids and dexamethasone
(approximately 4-6 hours after dosing) or if clinically unstable. Consider alternative agent
(e.g. anakinra or siltuximab) if persistent symptoms despite maximal dosing
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Principles of CRS Management With Bispecifics in NHL’
Grade 3
+ Emergent inpatient admission (floor or ICU)
* Tylenol
+ Dexamethasone (e.g. 10 mg IV Q 6 hours), until resolution to grade < 1, followed by taper
+ Evaluate for sepsis and consider empiric antibiotics
+ Administer tocilizumab and consider alternative agent (e.g. anakinra or siltuximab) if
persistent grade 3 CRS despite maximal dosing
Grade 4
* Inpatient admission to ICU
+ Tylenol
+ Dexamethasone (e.g. 20 mg IV Q 6 hours), until resolution to grade < 1, followed by taper
+ Administer tocilizumab and if repeated doses of tocilizumab have been utilized, consider
alternative agent (e.g. anakinra or siltuximab) if persistent grade 4 CRS despite maximal
dosing of first agent à vus vie W.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Grade 3
+ Emergent inpatient admission (floor or ICU)
* Tylenol
+ Dexamethasone (e.g. 10 mg IV Q 6 hours), until resolution to grade < 1, followed by taper
+ Evaluate for sepsis and consider empiric antibiotics
+ Administer tocilizumab and consider alternative agent (e.g. anakinra or siltuximab) if
persistent grade 3 CRS despite maximal dosing
Grade 4
* Inpatient admission to ICU
+ Tylenol
+ Dexamethasone (e.g. 20 mg IV Q 6 hours), until resolution to grade < 1, followed by taper
+ Administer tocilizumab and if repeated doses of tocilizumab have been utilized, consider
alternative agent (e.g. anakinra or siltuximab) if persistent grade 4 CRS despite maximal
dosing of first agent à vus vie W.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Safety Management and Implications
for Community Practice
+ CD20 x CD3 bispecifics have the potential to benefit patients with lymphoma
treated in communities where available
How to navigate the challenging step-up period?
— Consider collaboration with larger centers for step-up dosing
— Create bispecific treatment teams (eg, to deliver bispecifics in the
outpatient setting)
— Collaborate with nearby emergency departments
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for Community Practice
+ CD20 x CD3 bispecifics have the potential to benefit patients with lymphoma
treated in communities where available
How to navigate the challenging step-up period?
— Consider collaboration with larger centers for step-up dosing
— Create bispecific treatment teams (eg, to deliver bispecifics in the
outpatient setting)
— Collaborate with nearby emergency departments
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Neurologic Toxicity Is Rare
No driving restrictions for patients who feel well
No need for ongoing neurologic monitoring
If toxicity occurs, can manage as ICANs
Consider alternative causes
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No driving restrictions for patients who feel well
No need for ongoing neurologic monitoring
If toxicity occurs, can manage as ICANs
Consider alternative causes
PeerView.com
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Management Considerations for ICANS!
ICANS Grading Management
Grade 1: ICE 7-9 or depressed level of
consciousness but awakens spontaneously
Grade 2: ICE 3-6 or depressed level of
consciousness but awakens to voice
Grade 3: ICE 0-2 or depressed level of
consciousness but awakens to tactile
stimulus or any clinical seizure that
resolves rapidly or focal/local edema on
neuroimaging
Grade 4: ICE is O or patient is unarousable
or requires vigorous or repetitive tactile
stimuli, or life-threatening prolonged
seizure (>5 minutes) or repetitive seizures
without retum to baseline or deep focal
motor weakness or diffuse cerebral edema
‘on neuroimaging
1. Crombie J ot al Blood. 2024:143-1565-1975,
PeerView.com/KQE827
Pending clinical scenario and social situation, can consider observation or close monitoring in
outpatient setting. Can consider dexamethasone 10 mg x 1
‘Admit patient to hospital for monitoring
Dexamethasone 10 mg IV every 12 h, followed by taper once grade 21
Monitor in ICU setting
Neurology consult
Dexamethasone 10 mg IV every 6 h, followed by taper once grade 21
Use antiepileptics for seizure management as needed
Consider adding anakinra 100 mg every 12 h if symptoms persist beyond 24 h, continue until
resolution
+ Monitor in ICU setting
Neurology consult
Dexamethasone 10 mg IV every 6 h, followed by taper once grade 21
Use antiepileptics for seizure management as needed
+ Consider adding anakinra 100 mg every 12 h if symptoms persist beyond 24 h, continue
until resoluti
eervie
Copyright © 2000-2024, PeerView
ICANS Grading Management
Grade 1: ICE 7-9 or depressed level of
consciousness but awakens spontaneously
Grade 2: ICE 3-6 or depressed level of
consciousness but awakens to voice
Grade 3: ICE 0-2 or depressed level of
consciousness but awakens to tactile
stimulus or any clinical seizure that
resolves rapidly or focal/local edema on
neuroimaging
Grade 4: ICE is O or patient is unarousable
or requires vigorous or repetitive tactile
stimuli, or life-threatening prolonged
seizure (>5 minutes) or repetitive seizures
without retum to baseline or deep focal
motor weakness or diffuse cerebral edema
‘on neuroimaging
1. Crombie J ot al Blood. 2024:143-1565-1975,
PeerView.com/KQE827
Pending clinical scenario and social situation, can consider observation or close monitoring in
outpatient setting. Can consider dexamethasone 10 mg x 1
‘Admit patient to hospital for monitoring
Dexamethasone 10 mg IV every 12 h, followed by taper once grade 21
Monitor in ICU setting
Neurology consult
Dexamethasone 10 mg IV every 6 h, followed by taper once grade 21
Use antiepileptics for seizure management as needed
Consider adding anakinra 100 mg every 12 h if symptoms persist beyond 24 h, continue until
resolution
+ Monitor in ICU setting
Neurology consult
Dexamethasone 10 mg IV every 6 h, followed by taper once grade 21
Use antiepileptics for seizure management as needed
+ Consider adding anakinra 100 mg every 12 h if symptoms persist beyond 24 h, continue
until resoluti
eervie
Copyright © 2000-2024, PeerView
Key Principles for Infection Management
When Using Bispecific Antibodies in NHL
. Patients affected by COVID-19 should be managed as per local institutional
guidelines
> Individualized consultation with infectious disease experts to determine additional
therapies (if any) and a timing for resumption of therapy
. Hypogammaglobulinemia
> Monitor immunoglobulin levels
> Consider IV immunoglobulin replacement for individuals with recurrent infections
. PJP and varicella-zoster virus prophylaxis recommended
. In patients with a history of latent HBV, specific antiviral therapy is recommended
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When Using Bispecific Antibodies in NHL
. Patients affected by COVID-19 should be managed as per local institutional
guidelines
> Individualized consultation with infectious disease experts to determine additional
therapies (if any) and a timing for resumption of therapy
. Hypogammaglobulinemia
> Monitor immunoglobulin levels
> Consider IV immunoglobulin replacement for individuals with recurrent infections
. PJP and varicella-zoster virus prophylaxis recommended
. In patients with a history of latent HBV, specific antiviral therapy is recommended
PeerView.com
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Bispecifics in FL:
What Are the Next Steps?
What Are the Next Steps?
EPCORE NHL-2, Arm2b Cohort: The Epcoritamab and
R2 Combination Is Effective in R/R FL!
Dosing Regimen
for Epcoritamab +
R2 Combination
R2
After median follow-up
of 5.6 mo, the
combination showed
high overall and CMR
rate
+ mDOR, not
reached
Treatment Regimen for Epcoritamab SC 48 mg + R2
Epcoritamab Q4W up
SC 48 mg aw ow aaw aw aw aw | 02 years
Rituximab IV
375 mom aw aw aw aaw aw
Lenalidomide :
oral 20 mg Daily for 21 days (for 12 cycles)
Patients, %
1. Fah Let al. ASH 2022. Abstract 609.
PeerView.com/KQE827
ORR
83.5
CMR
so
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R2 Combination Is Effective in R/R FL!
Dosing Regimen
for Epcoritamab +
R2 Combination
R2
After median follow-up
of 5.6 mo, the
combination showed
high overall and CMR
rate
+ mDOR, not
reached
Treatment Regimen for Epcoritamab SC 48 mg + R2
Epcoritamab Q4W up
SC 48 mg aw ow aaw aw aw aw | 02 years
Rituximab IV
375 mom aw aw aw aaw aw
Lenalidomide :
oral 20 mg Daily for 21 days (for 12 cycles)
Patients, %
1. Fah Let al. ASH 2022. Abstract 609.
PeerView.com/KQE827
ORR
83.5
CMR
so
PeerView.com
Copyright © 2000-2024, PeerView
Next Steps With Odronextamab:
Phase 3 Combination Study in R/R FL
Phrase 3 OLYMPIA-5 Study Design
+ Part 1: Safety run-in
+ Part 2: Randomization
Odronextamab +
Patients with
RIR FL and
MZL
Rituximab +
lenalidomide:
for 12 cycle
Riuximab and lenaldomide on C15, followed by lenalidomide monotherapy on 08-12.
1. hips lcinicalrials govistudy/NCTOS 149286.
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Phase 3 Combination Study in R/R FL
Phrase 3 OLYMPIA-5 Study Design
+ Part 1: Safety run-in
+ Part 2: Randomization
Odronextamab +
Patients with
RIR FL and
MZL
Rituximab +
lenalidomide:
for 12 cycle
Riuximab and lenaldomide on C15, followed by lenalidomide monotherapy on 08-12.
1. hips lcinicalrials govistudy/NCTOS 149286.
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Bispecifics in the Frontline
EPCORE NHL-2, Arm 6*
A phase 1b/2, open-label trial evaluating the safety and antitumor activity of epcoritamab and
R? in adults with previously untreated FL
Expansion, N = 41
Key Inclusion Criteria Epcoritamab SC 48 mg
CON 2 01.2, AW C3+ treatment up to 2 year
a eo! ax NE ont 3 ee ay
burden, as determined by GELT cris á
+ ECOGPS0-2 5]
2 Measurable disease by CT or MRI ES Lenaidomide ora) 20 mg
+ Adequate organ function Ed a 2
+ Primary objectives: antitumor activity (ORR) and safety/tolerability Median flow, me fange) (14+ to 107)
+ Key secondary endpoints: DOR
Best Overall Response* Total Efficacy Evaluable, % (N = 36)
Based on mos response ovluae population done as patents wih 21 target sion a seine and 21 postbasclne response evaluation aná patonts who
‘ia within 60 days of fst dose. One patent died wihu 60 days of rs dose without assessment (COVID-19) ñ
1.Falchi etal. ASH 2022, Abstract 609. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
EPCORE NHL-2, Arm 6*
A phase 1b/2, open-label trial evaluating the safety and antitumor activity of epcoritamab and
R? in adults with previously untreated FL
Expansion, N = 41
Key Inclusion Criteria Epcoritamab SC 48 mg
CON 2 01.2, AW C3+ treatment up to 2 year
a eo! ax NE ont 3 ee ay
burden, as determined by GELT cris á
+ ECOGPS0-2 5]
2 Measurable disease by CT or MRI ES Lenaidomide ora) 20 mg
+ Adequate organ function Ed a 2
+ Primary objectives: antitumor activity (ORR) and safety/tolerability Median flow, me fange) (14+ to 107)
+ Key secondary endpoints: DOR
Best Overall Response* Total Efficacy Evaluable, % (N = 36)
Based on mos response ovluae population done as patents wih 21 target sion a seine and 21 postbasclne response evaluation aná patonts who
‘ia within 60 days of fst dose. One patent died wihu 60 days of rs dose without assessment (COVID-19) ñ
1.Falchi etal. ASH 2022, Abstract 609. PeerView.com
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Next Steps With Odronextamab:
Phase 3 Combination Study in Previously Untreated FL
Phase 3 OLYMPIA-1 Study Design Phase 3 OLYMPIA-2 Study Design
« Part 1: Safety run-in + Part 1: Safety run-in
+ Part 2: Randomization + Part 2: Randomization
Odronextamab-
Odronextamab for
no maintenanc
Odronextamab-
Patients with Patients with CHOP/odronextamab-CVP for
untreated FL untreated FL
Rituximab + investigato
choice for 6 cycle
1. Mps casse cnicatals goviet2/showNCTO6001254, 2. ts inicial govistuoyNCT06097364. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Phase 3 Combination Study in Previously Untreated FL
Phase 3 OLYMPIA-1 Study Design Phase 3 OLYMPIA-2 Study Design
« Part 1: Safety run-in + Part 1: Safety run-in
+ Part 2: Randomization + Part 2: Randomization
Odronextamab-
Odronextamab for
no maintenanc
Odronextamab-
Patients with Patients with CHOP/odronextamab-CVP for
untreated FL untreated FL
Rituximab + investigato
choice for 6 cycle
1. Mps casse cnicatals goviet2/showNCTO6001254, 2. ts inicial govistuoyNCT06097364. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Bispecifics in the Frontline
+ NCT05783596: Glofitamab plus obinutuzumab
in frontline FL/MZL
+ NCT05783609: Epcoritamab plus rituximab in
frontline FL
PeerView.com
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+ NCT05783596: Glofitamab plus obinutuzumab
in frontline FL/MZL
+ NCT05783609: Epcoritamab plus rituximab in
frontline FL
PeerView.com
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Revisiting Our Case
ht © 2000-2024, Peerview
ht © 2000-2024, Peerview
(&) Workshop Take-Homes:
Preparing for Next-Gen Bispecifics in FL
A 73-year-old woman with R/R FL previously treated with 1L CIT and evidence of POD24;
subsequently the patient receives R2 and responds but experiences neutropenia, managed with
GCSF; subsequent relapse, PS is now 2 and CAR-T has not been planned.
Options For a Patient With POD24 R/R FL In Need of 3L Treatment Who Is Not Pursuing CAR-T
Bispecifics are approved in 3rd line and can be considered for this patient with R/R FL
Emerging bispecifics likely represent future options, including in poor prognosis POD24 settings
CD20 x CD3 bispecifics may have particular relevance for FL care in the community setting
+ Be prepared to collaborate with other members of the healthcare team, academic centers, and ED
Studies of bispecifics in combination with other agents and in earlier lines of therapy are underway
PeerView.com
PeerView.com/KQE827 Copyright O 2000-2024, Peerview
Preparing for Next-Gen Bispecifics in FL
A 73-year-old woman with R/R FL previously treated with 1L CIT and evidence of POD24;
subsequently the patient receives R2 and responds but experiences neutropenia, managed with
GCSF; subsequent relapse, PS is now 2 and CAR-T has not been planned.
Options For a Patient With POD24 R/R FL In Need of 3L Treatment Who Is Not Pursuing CAR-T
Bispecifics are approved in 3rd line and can be considered for this patient with R/R FL
Emerging bispecifics likely represent future options, including in poor prognosis POD24 settings
CD20 x CD3 bispecifics may have particular relevance for FL care in the community setting
+ Be prepared to collaborate with other members of the healthcare team, academic centers, and ED
Studies of bispecifics in combination with other agents and in earlier lines of therapy are underway
PeerView.com
PeerView.com/KQE827 Copyright O 2000-2024, Peerview
Next Steps in Multiple Myeloma
The Coming Wave of BCMA
Bispecific Antibodies
Sundar Jagannath, MD, FASCO
Professor of Medicine 5 à |
Icahn School of Medicine at Mount Sinai
New York, New York A
The Coming Wave of BCMA
Bispecific Antibodies
Sundar Jagannath, MD, FASCO
Professor of Medicine 5 à |
Icahn School of Medicine at Mount Sinai
New York, New York A
(&) Workshop: A Patient With Triple-Class
Refractory MM and High-Risk Features
Scott originally presented with high-risk MM
+ 1921 amplification (2 extra copies), +11, del(13q) He is now 80 years old
Treatment history with RRMM and a short
DOR after his most recent
+ D-RVd, then ASCT, then R maintenance progression
+ D-Pd: best response PR; DOR = 11 months
+ KCd: best response PR; DOR = 6 months
+ Selinexor-Kd: PR; DOR = 2 months (CAR-T has not been planned)
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Refractory MM and High-Risk Features
Scott originally presented with high-risk MM
+ 1921 amplification (2 extra copies), +11, del(13q) He is now 80 years old
Treatment history with RRMM and a short
DOR after his most recent
+ D-RVd, then ASCT, then R maintenance progression
+ D-Pd: best response PR; DOR = 11 months
+ KCd: best response PR; DOR = 6 months
+ Selinexor-Kd: PR; DOR = 2 months (CAR-T has not been planned)
PeerView.com
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(&) Workshop: A Patient With Triple-Class
Refractory MM and High-Risk Features
Scott originally presented with high-risk MM
+ 1921 amplification (2 extra copies), +11, del(13q) He is now 80 years old
Treatment history with RRMM and a short
DOR after his most recent
+ D-RVd, then ASCT, then R maintenance progression
+ D-Pd: best response PR; DOR = 11 months
+ KCd: best response PR; DOR = 6 months
+ Selinexor-Kd: PR; DOR = 2 months (CAR-T has not been planned)
Points to consider
+ Isittoo late for CAR-T or can you wait?
+ Is there a role for BCMA bispecifics?
+ BCMA or another antigen target?
+ Emerging BCMA bispecifics—what will their role be?
PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Refractory MM and High-Risk Features
Scott originally presented with high-risk MM
+ 1921 amplification (2 extra copies), +11, del(13q) He is now 80 years old
Treatment history with RRMM and a short
DOR after his most recent
+ D-RVd, then ASCT, then R maintenance progression
+ D-Pd: best response PR; DOR = 11 months
+ KCd: best response PR; DOR = 6 months
+ Selinexor-Kd: PR; DOR = 2 months (CAR-T has not been planned)
Points to consider
+ Isittoo late for CAR-T or can you wait?
+ Is there a role for BCMA bispecifics?
+ BCMA or another antigen target?
+ Emerging BCMA bispecifics—what will their role be?
PeerView.com
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What Is the Current
Experience With
Established BCMA
Bispecifics?
Experience With
Established BCMA
Bispecifics?
Bispecific Antibodies Result in T-Cell Activation and
Subsequent Lysis of BCMA-Expressing MM Cells‘
Teclistamab binds to CD3 on Talquetamab targets CD3
T cells and BCMA on plasma cells and GPRC5D
Talguetamab
(GPRCSO" COD otto
Le
Elranatamab: a humanized
bispecific targeting BCMA and CD3
1.Nocka A et. ASCO 2022. Abstract 8007, 2. Jakubowiak AJ etal. ASCO 2022, Abstract 8014. 3. Char A ot al. N Engl J Med. 2022:387:2232-2244, PeerView.com
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Subsequent Lysis of BCMA-Expressing MM Cells‘
Teclistamab binds to CD3 on Talquetamab targets CD3
T cells and BCMA on plasma cells and GPRC5D
Talguetamab
(GPRCSO" COD otto
Le
Elranatamab: a humanized
bispecific targeting BCMA and CD3
1.Nocka A et. ASCO 2022. Abstract 8007, 2. Jakubowiak AJ etal. ASCO 2022, Abstract 8014. 3. Char A ot al. N Engl J Med. 2022:387:2232-2244, PeerView.com
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NCCN Guidelines Recommend
Bispecific Antibodies for Late Relapses'
Therapies for Patients With Late Relapses (>3 Prior Therapies)
Preferred Regimens
After at least 4 prior therapies, including an anti-CD38 monoclonal
antibody, a Pl, and an IMiD
CAR-T cell therapy Bispecific antibodies
+ Ciltacabtagene autoleucel + Elranatamab-bcmm
+ Idecabtagene vicleucel + Talquetamab-tgvs
+ Teclistamab-cq
1. NCCN Clinical Practice Guidelines in Oncology. Mutiple Myeloma. Version 3.2024. ps: nccn org/professionalsphysician_glspdtimyeloma pat PeerView.com
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Bispecific Antibodies for Late Relapses'
Therapies for Patients With Late Relapses (>3 Prior Therapies)
Preferred Regimens
After at least 4 prior therapies, including an anti-CD38 monoclonal
antibody, a Pl, and an IMiD
CAR-T cell therapy Bispecific antibodies
+ Ciltacabtagene autoleucel + Elranatamab-bcmm
+ Idecabtagene vicleucel + Talquetamab-tgvs
+ Teclistamab-cq
1. NCCN Clinical Practice Guidelines in Oncology. Mutiple Myeloma. Version 3.2024. ps: nccn org/professionalsphysician_glspdtimyeloma pat PeerView.com
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NCCN Guidelines Recommend
Bispecific Antibodies for Late Relapses'
Therapies for Patients With Late Relapses (>3 Prior Therapies)
Preferred Regimens
After at least 4 prior therapies, including an anti-CD38 monoclonal
antibody, a Pl, and an IMiD
Supported by MagnetisMM-3: Bispecific antibodies
+ ORR (no prior BCMA): 61% =>* Elranatamab-bcmm
ORR (BCMA exposed): 46%? + Talquetamab-tgvs
Median PFS: 17.2 months? + Teclistamab-cqyv
2 omasson eral ASM 2028 Aura 30888. Nook A oa ASC 2008 Anne ww Peesonsephysien.paimydlona pa PeerView.com
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Bispecific Antibodies for Late Relapses'
Therapies for Patients With Late Relapses (>3 Prior Therapies)
Preferred Regimens
After at least 4 prior therapies, including an anti-CD38 monoclonal
antibody, a Pl, and an IMiD
Supported by MagnetisMM-3: Bispecific antibodies
+ ORR (no prior BCMA): 61% =>* Elranatamab-bcmm
ORR (BCMA exposed): 46%? + Talquetamab-tgvs
Median PFS: 17.2 months? + Teclistamab-cqyv
2 omasson eral ASM 2028 Aura 30888. Nook A oa ASC 2008 Anne ww Peesonsephysien.paimydlona pa PeerView.com
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NCCN Guidelines Recommend
Bispecific Antibodies for Late Relapses'
Therapies for Patients With Late Relapses (>3 Prior Therapies)
Preferred Regimens
After at least 4 prior therapies, including an anti-CD38 monoclonal
antibody, a Pl, and an IMiD
Supported by MajesTEC-1: Bispecific antibodies
+ ORR 63% (no prior BCMA)2 + Elranatamab-bemm
ORR 59% (BCMA exposed)? + Talquetamab-tgvs
Median PFS: 11.3 months? =) » Teclistamab-cqyv
1. NCCN Cinca race Guideines in Oncology. Muto Myeloma. Version 3.2024. ps: non orrotessinalspryacian_glpclmyeloma pat ra
2 Van de Donk N et a. ASCO 2023. Abstract 8011. 3. Dima D eta. Transplant Coll Ther. 2024;30:208 01-008 013. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Bispecific Antibodies for Late Relapses'
Therapies for Patients With Late Relapses (>3 Prior Therapies)
Preferred Regimens
After at least 4 prior therapies, including an anti-CD38 monoclonal
antibody, a Pl, and an IMiD
Supported by MajesTEC-1: Bispecific antibodies
+ ORR 63% (no prior BCMA)2 + Elranatamab-bemm
ORR 59% (BCMA exposed)? + Talquetamab-tgvs
Median PFS: 11.3 months? =) » Teclistamab-cqyv
1. NCCN Cinca race Guideines in Oncology. Muto Myeloma. Version 3.2024. ps: non orrotessinalspryacian_glpclmyeloma pat ra
2 Van de Donk N et a. ASCO 2023. Abstract 8011. 3. Dima D eta. Transplant Coll Ther. 2024;30:208 01-008 013. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Step-Up and Subsequent Dosing for Teclistamab!
Dosing Schedule Day Dose
Step-up 4 Step-up dose 1 0.06 mg/kg
dosing schedule 4 Step-up dose 2 0.3 mg/kg
(48-hour
hospitalization after 7 First treatment dose 1.5 mg/kg
each SZ dose)
Weekly 1 week after first treatment dose and weekly 1.5 mg/kg
dosing schedule thereafter once weekly
Dune edule For patients who have achieved and 1.5 mg/kg every
9 maintained 2CR for a minimum of 6 months 2 weeks
Step-up doses may be administered between 2 to 4 days after the previous dose and may | PMI
be given up to 7 days after the previous dose to allow for resolution of any adverse reactions | Mil Zul
1. Tecvayl (teclstamab) Prescribing information, ps www accessdata da govldngsatiéa_docsfabel2028/7612018004i pt. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Dosing Schedule Day Dose
Step-up 4 Step-up dose 1 0.06 mg/kg
dosing schedule 4 Step-up dose 2 0.3 mg/kg
(48-hour
hospitalization after 7 First treatment dose 1.5 mg/kg
each SZ dose)
Weekly 1 week after first treatment dose and weekly 1.5 mg/kg
dosing schedule thereafter once weekly
Dune edule For patients who have achieved and 1.5 mg/kg every
9 maintained 2CR for a minimum of 6 months 2 weeks
Step-up doses may be administered between 2 to 4 days after the previous dose and may | PMI
be given up to 7 days after the previous dose to allow for resolution of any adverse reactions | Mil Zul
1. Tecvayl (teclstamab) Prescribing information, ps www accessdata da govldngsatiéa_docsfabel2028/7612018004i pt. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Teclistamab Safety and Other Practical Points
AEs of Interest! Comments
Key infections
Respiratory (56%)
COVID-19 (27%)
Other viral (10%)
Gl (8%)
Fungal (5%)
PJP (4%)
Hepatitis B (0.6%)
+ Only 0.6% of CRS were grade 3
+ No grade 4/5 CRS events
Infections 78%
CRS 72%
Other considerations"?
+ ICANS was reported in 3% of patients
+ CBC at baseline and periodically during treatment
* Ifadministration-related reactions and local injection-site reactions occur, withhold or consider
discontinuation based on severity
4. Van de Donk N et a. ASCO 2023. Abstract 8011.2. Tecvay('ocistamab) Proscriding Information, u
ps www. accessdat fda govirugsatida_docslabel2023/761291s0040 pat PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
AEs of Interest! Comments
Key infections
Respiratory (56%)
COVID-19 (27%)
Other viral (10%)
Gl (8%)
Fungal (5%)
PJP (4%)
Hepatitis B (0.6%)
+ Only 0.6% of CRS were grade 3
+ No grade 4/5 CRS events
Infections 78%
CRS 72%
Other considerations"?
+ ICANS was reported in 3% of patients
+ CBC at baseline and periodically during treatment
* Ifadministration-related reactions and local injection-site reactions occur, withhold or consider
discontinuation based on severity
4. Van de Donk N et a. ASCO 2023. Abstract 8011.2. Tecvay('ocistamab) Proscriding Information, u
ps www. accessdat fda govirugsatida_docslabel2023/761291s0040 pat PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Step-Up and Subsequent Dosing for Elranatamab*
Dosing Schedule Day Dose
1 Step-up dose 1 ] 12 mg
48-hour hospitalization
Step-up dosing 4 Step-up dose 2 32mg
schedule 24 hour hospitalization
8 First treatment dose 76 mg
1 week after first
Weekly dosing treatment dose and Subsequent treatment 76 mi
schedule weekly thereafter doses 9
through week 24
Biweekly dosing Week 25 and every 2 Subsequent treatment 76 mg
schedule weeks thereafter doses
1. Eten (eranalamab bemm) Prosenbing Information hips ww access:
PeerView.com/KQE827
a goviérugsaiéa_docsAabel/2023/76 1345018000 pe.
Download the
Practice Aid!
PeerView.com
Copyright © 2000-2024, PeerView
Dosing Schedule Day Dose
1 Step-up dose 1 ] 12 mg
48-hour hospitalization
Step-up dosing 4 Step-up dose 2 32mg
schedule 24 hour hospitalization
8 First treatment dose 76 mg
1 week after first
Weekly dosing treatment dose and Subsequent treatment 76 mi
schedule weekly thereafter doses 9
through week 24
Biweekly dosing Week 25 and every 2 Subsequent treatment 76 mg
schedule weeks thereafter doses
1. Eten (eranalamab bemm) Prosenbing Information hips ww access:
PeerView.com/KQE827
a goviérugsaiéa_docsAabel/2023/76 1345018000 pe.
Download the
Practice Aid!
PeerView.com
Copyright © 2000-2024, PeerView
Elranatamab Safety and Other Practical Points
AEs of Interest! Overall (All-Grade) Comments
+ Grade 3/4 infections (47.2%)
+ COVID-19 was the most
Infections 69.9% frequently reported (29.3%)
CRS 57.7% + No grade 3/4 CRS
Other considerations'*
+ ICANS was reported in 4.9% of patients
+ Monitor CBC at baseline and periodically during treatment
+ Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated
for hepatotoxicity (elevated ALT, AST, and bilirubin)
4. Lesokhin A et al. Nat Mod. 202329259-2267. 2. Tomasson M etal. ASH 2023. Abstract 3385.3. Er (eranatamab-demm) Preserbing information,
pS www accossdata da govidnigsatia_docs/abel 2023761345019 1s00081 pl. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
AEs of Interest! Overall (All-Grade) Comments
+ Grade 3/4 infections (47.2%)
+ COVID-19 was the most
Infections 69.9% frequently reported (29.3%)
CRS 57.7% + No grade 3/4 CRS
Other considerations'*
+ ICANS was reported in 4.9% of patients
+ Monitor CBC at baseline and periodically during treatment
+ Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated
for hepatotoxicity (elevated ALT, AST, and bilirubin)
4. Lesokhin A et al. Nat Mod. 202329259-2267. 2. Tomasson M etal. ASH 2023. Abstract 3385.3. Er (eranatamab-demm) Preserbing information,
pS www accossdata da govidnigsatia_docs/abel 2023761345019 1s00081 pl. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Key Points for Infection Management
With BCMA Bispecific Antibodies
Q Preventive protocols are key
Q PJP prophylaxis (eg, TMP/SMX, pentamidine)
Q HSV/VZV viral prophylaxis
Q_IVIG supplementation
Recommendations on prevention of infections during chimeric
antigen receptor T-cell and bispecific antibody therapy in
multiple myeloma
Meera Mohan, Rajshekhar Chakraborty, Susan Bal, Anoma Nellore, Muhamed Baljevic, Anta D'Souza,
Peter G. Pappas, Jesus G. Berdeja, Natalie Callander, Luciano). Costa
Recommendations Are Available!
1. Mohan M et al. Br J Haomatol. 2023:203:736-748, PeerView.com
Peerview.com/KQE827 Copyright O 2000-2024, Peerview
With BCMA Bispecific Antibodies
Q Preventive protocols are key
Q PJP prophylaxis (eg, TMP/SMX, pentamidine)
Q HSV/VZV viral prophylaxis
Q_IVIG supplementation
Recommendations on prevention of infections during chimeric
antigen receptor T-cell and bispecific antibody therapy in
multiple myeloma
Meera Mohan, Rajshekhar Chakraborty, Susan Bal, Anoma Nellore, Muhamed Baljevic, Anta D'Souza,
Peter G. Pappas, Jesus G. Berdeja, Natalie Callander, Luciano). Costa
Recommendations Are Available!
1. Mohan M et al. Br J Haomatol. 2023:203:736-748, PeerView.com
Peerview.com/KQE827 Copyright O 2000-2024, Peerview
Principles for Choosing Between Bispecifics
and CAR-T and Evidence for Sequential Care
Candidates for « With RRMM progressing after 3-5 prior LOT who are unable to access
BCMA bispecifics CAR-T or at high-risk of manufacturing failure
can include e With rapidly progressing/aggressive MM (unable to wait for CAR-T)
patients ...
« Failing treatment with CAR-T
To date sequencing between BCMA platforms appears to be an active approach in RRMM
CAR-T BCMA TCE
ORR 53%! ORR 57%?
1.Nocka A et al. ASCO 2023. Abstract 8008.2. Cohen AD eta. Blood. 2023,141:219-230, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
and CAR-T and Evidence for Sequential Care
Candidates for « With RRMM progressing after 3-5 prior LOT who are unable to access
BCMA bispecifics CAR-T or at high-risk of manufacturing failure
can include e With rapidly progressing/aggressive MM (unable to wait for CAR-T)
patients ...
« Failing treatment with CAR-T
To date sequencing between BCMA platforms appears to be an active approach in RRMM
CAR-T BCMA TCE
ORR 53%! ORR 57%?
1.Nocka A et al. ASCO 2023. Abstract 8008.2. Cohen AD eta. Blood. 2023,141:219-230, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Further Thoughts on Sequencing
Post-bispecific antibody therapy failure
+ Relapse is on therapy
+ Tumor antigen down regulated or mutated
+ Retreatment with bispecifics against
different tumor antigen
+ Immune environment includes T cell
exhaustion or upregulation of Treg
+ Failure to generate CAR-T cells
Post CAR-T failure
+ Relapse is off treatment
+» The later the relapse, the better the
T-cell fitness
ea O Relapse — + BCMA is still expressed on the tumor
+ Retreatment with bispecifics is successful
+ Retreatment with same CAR-T for relapse
fails if ADA is detected
On Treatment
CAR-T infusion
PeerView.com
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Post-bispecific antibody therapy failure
+ Relapse is on therapy
+ Tumor antigen down regulated or mutated
+ Retreatment with bispecifics against
different tumor antigen
+ Immune environment includes T cell
exhaustion or upregulation of Treg
+ Failure to generate CAR-T cells
Post CAR-T failure
+ Relapse is off treatment
+» The later the relapse, the better the
T-cell fitness
ea O Relapse — + BCMA is still expressed on the tumor
+ Retreatment with bispecifics is successful
+ Retreatment with same CAR-T for relapse
fails if ADA is detected
On Treatment
CAR-T infusion
PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Preparing for the
Next Generation of
BCMA Bispecifics
Next Generation of
BCMA Bispecifics
Other BCMA and Novel MOA Bispecifics in Development!
Bispecific Antibody Target Format
BCMA x CD3
Linvoseltamab Under priority review at the FDA for adult patients
with RRMM who have previously received 23 LOT
ABBV-383 BCMA x CD3; IgG4
Cevostamab FcRH5 x CD3 humanized IgG1
1. Lejeune M et a. Front Immunol 2020:11:762. 2. Laneman G eta. Blood Cancer Discov. 2021:2:423-433.3. Hosny M at al J Clin Mod. 2021:10:4583
Blood 7
4 Moreau P, Touzeau €. Blood. 2022,139:3681-3687, 5. Lesokhin AM et al. ASH 2022. Abstract 1924 PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Bispecific Antibody Target Format
BCMA x CD3
Linvoseltamab Under priority review at the FDA for adult patients
with RRMM who have previously received 23 LOT
ABBV-383 BCMA x CD3; IgG4
Cevostamab FcRH5 x CD3 humanized IgG1
1. Lejeune M et a. Front Immunol 2020:11:762. 2. Laneman G eta. Blood Cancer Discov. 2021:2:423-433.3. Hosny M at al J Clin Mod. 2021:10:4583
Blood 7
4 Moreau P, Touzeau €. Blood. 2022,139:3681-3687, 5. Lesokhin AM et al. ASH 2022. Abstract 1924 PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Structure and MOA of Linvoseltamab'
+ Linvoseltamab: a BCMA x CD3 bispecific antibody
+ Targets T-cell effector function to induce cytotoxicity of
BCMA-expressing MM cells
Linvoseltamab MOA
REGN5458
Linvoseltamab Molecular Structure (BCMAX CDS bispectc
Fab regions, Qo
—— 4
con N Activated
binding — — binding Pr
site site
—
Veloci-Bi Variable
Fc region region
1. Zonder JA et al, EHA 2022. Abstract $189, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
+ Linvoseltamab: a BCMA x CD3 bispecific antibody
+ Targets T-cell effector function to induce cytotoxicity of
BCMA-expressing MM cells
Linvoseltamab MOA
REGN5458
Linvoseltamab Molecular Structure (BCMAX CDS bispectc
Fab regions, Qo
—— 4
con N Activated
binding — — binding Pr
site site
—
Veloci-Bi Variable
Fc region region
1. Zonder JA et al, EHA 2022. Abstract $189, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Emerging BCMA Bispecifics: Updates on Linvoseltamab
LINKER-MM1 study tested IV linvoseltamab at 80
the recommended 200 mg dose in patients ORR: 69.2% "PR
with RRMM (N = 117)! e EVER
Efficacy findings (after median follow-up of en
11.1 months)? $
+ ORR: 69.2% ¿
+ 59% achieved 2VGPR 2
+ Among patients with CR or sCR with =
available MRD data (N = 37), SCR
50% were MRD negative at 105 39%
Median DOR and PFS not reached?
200 mg (N = 117)
1. Lee HC et al ASCO 2023. Abstract 8006. 2. Jagannath St al. ASH 2023. Abstract 4746. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
LINKER-MM1 study tested IV linvoseltamab at 80
the recommended 200 mg dose in patients ORR: 69.2% "PR
with RRMM (N = 117)! e EVER
Efficacy findings (after median follow-up of en
11.1 months)? $
+ ORR: 69.2% ¿
+ 59% achieved 2VGPR 2
+ Among patients with CR or sCR with =
available MRD data (N = 37), SCR
50% were MRD negative at 105 39%
Median DOR and PFS not reached?
200 mg (N = 117)
1. Lee HC et al ASCO 2023. Abstract 8006. 2. Jagannath St al. ASH 2023. Abstract 4746. PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Preparing for Linvoseltamab Step-Up Dosing’
Linvoseltamab Is Administered Using a Step-up IV Dosing Schedule
Weeks 1-2 Weeks 3-14 Weeks 16-23 Week 24 onward
Step-up doses 200 mg 200 mg 200 mg
CHOLET) 2VGPR: every 4 weeks
Once a week Every 2 weeks
Day1 Day8 <VGPR: every 2 weeks
24-hour hospitalization
Customized
Predictable timing and low rate dosing based
of CRS allows for an inpatient Download the
monitoring schedule of 1 day on depth of Practice Aid!
response
at week 1 and week 2
1.Bumma N et al. ASH 2022, Abstract 4555. 2. Jagannath $ et al. ACR 2024. Abstract CTOO1, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Linvoseltamab Is Administered Using a Step-up IV Dosing Schedule
Weeks 1-2 Weeks 3-14 Weeks 16-23 Week 24 onward
Step-up doses 200 mg 200 mg 200 mg
CHOLET) 2VGPR: every 4 weeks
Once a week Every 2 weeks
Day1 Day8 <VGPR: every 2 weeks
24-hour hospitalization
Customized
Predictable timing and low rate dosing based
of CRS allows for an inpatient Download the
monitoring schedule of 1 day on depth of Practice Aid!
response
at week 1 and week 2
1.Bumma N et al. ASH 2022, Abstract 4555. 2. Jagannath $ et al. ACR 2024. Abstract CTOO1, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
What Is the Safety Experience With Linvoseltamab?!
CRS Grade, 200 mg Cohort
Most CRS occurred in the
step-up dosing period
1 patient with grade 3 CRS
mGrade 1 mGrade 2 =Grade 3
No grade 24 CRS reported
CRS onset usually occurred
on the day of dosing with
resolution within 1 day
Of those patients with CRS,
the majority were grade 1
5mg 25mg — FirstFull Second Full Third Full
Priming Intermediate Dose Dose Dose and
Dose Dose Beyond
1. Jagannath 8 tal. AACR 2024. Abstract CTOO1 PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
CRS Grade, 200 mg Cohort
Most CRS occurred in the
step-up dosing period
1 patient with grade 3 CRS
mGrade 1 mGrade 2 =Grade 3
No grade 24 CRS reported
CRS onset usually occurred
on the day of dosing with
resolution within 1 day
Of those patients with CRS,
the majority were grade 1
5mg 25mg — FirstFull Second Full Third Full
Priming Intermediate Dose Dose Dose and
Dose Dose Beyond
1. Jagannath 8 tal. AACR 2024. Abstract CTOO1 PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Other Safety and Practical Points With Linvoseltamab!
Other AEs of Interest Overall
From LINKER-MM1 (All-Grade) Gomments
+ Grades 3/4 in 34%
+ Infection frequency and severity decreased
Infections 73% over time
+ All cases of PJP occurred prior to mandatory
prophylaxis
ICANS 7.7% * Concurrent with CRS or IRRs
1. Jagannath et al, AACR 2024. Abstract CTOO1, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
Other AEs of Interest Overall
From LINKER-MM1 (All-Grade) Gomments
+ Grades 3/4 in 34%
+ Infection frequency and severity decreased
Infections 73% over time
+ All cases of PJP occurred prior to mandatory
prophylaxis
ICANS 7.7% * Concurrent with CRS or IRRs
1. Jagannath et al, AACR 2024. Abstract CTOO1, PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, PeerView
ABBV-383: Background and MOA
A
N ABBV-383 is uniquely
designed with Intended to
2 BCMA binding Bind with high affinity
domains to cell surface BCMA
N Low-affinity CD3 Induce lower
binding domain cytokine release
O c Silenced-Fc Extend the half-life with
backbone convenient dosing
==
c
PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
A
N ABBV-383 is uniquely
designed with Intended to
2 BCMA binding Bind with high affinity
domains to cell surface BCMA
N Low-affinity CD3 Induce lower
binding domain cytokine release
O c Silenced-Fc Extend the half-life with
backbone convenient dosing
==
c
PeerView.com
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
ABBV-383 Efficacy and Safety at Multiple Doses in
RRMM, Including Once Monthly Dosing
N = 220 Patients With RRMM Were Treated With ABBV-383'
Low CD3 affinity binding of ABBV-383 + modified dexamethasone premedication schedule appears to
msCRCR pe
%
mvcrr _ 8
En
PR 2
= ¿o
go
Bo
¿o
»
10
o
ORR 44%
2VGPR 22%
20 mg
GW
Dosing regimen of 60
mg Q4W does not
require step-up dosing
contribute to lower incidence (43%) and severity (Grade 1, 38%; Grade 2, 5%) of CRS at 60 mg Q4W
1. Vj Retal. ASH 2023 Abstract 3978.
PeerView.com/KQE827
PeerView.com
Copyright © 2000-2024, Peerview
RRMM, Including Once Monthly Dosing
N = 220 Patients With RRMM Were Treated With ABBV-383'
Low CD3 affinity binding of ABBV-383 + modified dexamethasone premedication schedule appears to
msCRCR pe
%
mvcrr _ 8
En
PR 2
= ¿o
go
Bo
¿o
»
10
o
ORR 44%
2VGPR 22%
20 mg
GW
Dosing regimen of 60
mg Q4W does not
require step-up dosing
contribute to lower incidence (43%) and severity (Grade 1, 38%; Grade 2, 5%) of CRS at 60 mg Q4W
1. Vj Retal. ASH 2023 Abstract 3978.
PeerView.com/KQE827
PeerView.com
Copyright © 2000-2024, Peerview
Workshop: Revisiting Our Patient
With High-Risk, TCR Myeloma
Scott originally presented with high-risk MM
+ 1921 amplification (2 extra copies), +11, del(13q)
Treatment history
+ D-RVd, then ASCT, then R maintenance
He is now 80 years old
with RRMM and a short
DOR after his most recent
+ D-Pd: best response PR; DOR = 11 months progression
+ KCd: best response PR; DOR = 6 months
+ Selinexor-Kd: PR; DOR = 2 months (CAR-T has not been planned)
Recommendations for Scott, a Patient Wit
For this patient with an aggressive relapse, waiting for CAR-T is suboptimal
Bispecifics represent effective options, particularly since he is BCMA-naïve
Understand the principles of delivering bispecifics in MM:
hospitalization/step-up, then weekly dosing, then subsequent modifications
Emerging bispecifics will offer expanded options and possibly more flexible dosing/delivery
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
With High-Risk, TCR Myeloma
Scott originally presented with high-risk MM
+ 1921 amplification (2 extra copies), +11, del(13q)
Treatment history
+ D-RVd, then ASCT, then R maintenance
He is now 80 years old
with RRMM and a short
DOR after his most recent
+ D-Pd: best response PR; DOR = 11 months progression
+ KCd: best response PR; DOR = 6 months
+ Selinexor-Kd: PR; DOR = 2 months (CAR-T has not been planned)
Recommendations for Scott, a Patient Wit
For this patient with an aggressive relapse, waiting for CAR-T is suboptimal
Bispecifics represent effective options, particularly since he is BCMA-naïve
Understand the principles of delivering bispecifics in MM:
hospitalization/step-up, then weekly dosing, then subsequent modifications
Emerging bispecifics will offer expanded options and possibly more flexible dosing/delivery
PeerView.com/KQE827 Copyright © 2000-2024, Peerview
Audience Q&A O |
Copyright © 2000-2024, PeerView
Copyright © 2000-2024, PeerView
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