Taking a BiTE Out of SCLC: Are You Ready for a New Wave of DLL3-Targeting T-Cell Engagers and Other Therapies?

Chair Taofeek K. Owonikoko, MD, PhD, discusses small cell lung cancer in this CME/AAPA activity titled “Taking a BiTE Out of SCLC: Are You Ready for a New Wave of DLL3-Targeting T-Cell Engagers and Other Therapies?” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/44I0Gjs. CME/AAPA credit will be available until September 29, 2025.

1. Taking a BiTE Out of SCLC

Are You Ready for a New Wave of
DLL3-Targeting T-Cell Engagers and Other Therapies?

Taofeek K. Owonikoko, MD, PhD
“The Marlene and Stewart Greenebaum Distinguished Professor in Oncology
est

Executive Director of the University of Maryland's Marlene and Stewart Greenebaum
| Comprehensive Cancer Center

Senior Associate Dean of Cancer Programs, University of Maryland School of Medicine

Associate Vice President of Cancer Programs, University of Maryland, Baltimore
Baltimore, Maryland

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2. Our Goals for Today

Equip you with knowledge of the rationale for use, characteristics, and
mechanism of action of DLL3-targeted T-cell engagers and other new
therapies in SCLC

Enhance your awareness of the latest data from clinical trials assessing
DLL3-targeted T-cell engagers and other therapies in SCLC.

Augment your ability to integrate novel DLL3-targeted T-cell engagers and
other therapies into individualized treatment plans for patients with SCLC

3. Addressing Unmet Needs and Opportunities for
Improvement in ES-SCLC With DLL3-Targeted
T-Cell Engagers and Other Novel Therapies

PS
7

Taofeek K. Owonikoko, MD, PhD

The Marlene and Stewart Greenebaum Distinguished Professor in Oncology

Executive Director of the University of Maryland's Marlene and Stewart Greenebaum
Comprehensive Cancer Center

Senior Associate Dean of Cancer Programs, University of Maryland School of Medicine
Associate Vice President of Cancer Programs, University of Maryland, Baltimore
Baltimore, Maryland

Go online to access full CME/AAPA information, including faculty disclosures.

Copyright

4. Barriers to Advances, Unmet Needs,
and Opportunities for Improvement in SCLC

Failed randomized trials

|

tandard chemotherapy eas} No extension
(fewer referr of patient survival
(>
Particularly in 2L.
‘and beyond

‘Several factors are thought to contribute to immunotherapy resistance in SCLC, including downregulation of major histacompatibilty
complex (MHC) molecules, failure of antigen presentation, and high intratumoral heterogeneity

Y

One strategy to bypass the lack of canonical antigen presentation pathways is to target alternative cell surface proteins on cancer cells

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5. Rationale for Targeting DLL31-4

+ Delta-like ligand 3 (DLL3), a protein that inhibits Notch signaling, is typically localized
intracellularly in normal cells but is abnormally expressed on the surface of SCLC

+ DLLS is expressed in 85%-94% of patients with SCLC, making it a rational target
for treatment

DLL3 expression in normal (A) and tumor (B) tissue via immunostaining (brown color)

1. Gin Mi et a cin Cancer Rs. 202127:1526-1637.2 Roo et al Lng Cancer 2020-47 27-23. 3 Passes Le a. J Cin Oncol 2025:4:2880-2903
4. Rudin GM et al J Homatol Oncol, 2023:16:56 PeerView.com

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6. Inflaming the Uninflamed: DLL3 Targeting’

DLL3 expression is greatest in
Ae 4 t titt immune checkpoint inhibitor-resistant SCLC

DLL3 is most highly expressed among those subtypes
least inf jor microenvironments

IMpower133 OS by Subtype

Den can 05,00 Checkttate 032: Analysis of inflammation and Antigen Presentation
women EF Macs ‘Signatures by Subtype and by Differential YAPY Expression
ns os

Immune cells (eg, T cels,
‘macrophages, NK cells)

EMT, IFNy signaling, and immune col infitrate
1. Gay et al Concer Ce. 2021; 30(9}346-300.e7.2. Rudin CM etal. J Thorac Oncol. 2023:18:1222-1232 PeerView.com

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7. Overview of DLL3 T-Cell Engager Pipeline’

Tarlatamab BI 764532 HPN328

DLL3-binding CD3-binding DLL3-binding
jon region CD3-targeting
domains regi be
CD3targeting
domains

Antialbumin

domain

Foregion
Fo region

DLL3argeting

‘domain

1. Rudin CH et al J Hemato Oncol 2023:166, PeerView.com

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8. Overview of the MOA of T-Cell Engagers'

T-Cell Engager T-Cell Proliferation
‘cDs-bindng region TAAbindng region ya.
Teel activation and
expansion
DI =
>
Feregion
cols engage
tumorassoested
Tumor cell antigen
>
Release of perforin and granzymes leading
to tumor cell lysis
1. Rudin CM eta. J Hematol Oncol. 2023:16:6. PeerView.com

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9. Focus on the Structure and MOA of Tarlatamab1?

+ A bispecific T-cell engager
immunotherapy that directs the
patient's T cells to cancer cells
expressing DLL3, independent of
MHC class

* Binds to both DLL3 on cancer cells
and CD3 on T cells, leading to T- Sie
cell-mediated lysis of cancer cells

Let’s now watch a 3D animation depicting how
tarlatamab works in more detail

1. Gin M etal. Gin Cancer Ros. 2021:27:1526-1697. 2. Rojo F et al. Lung Cancer 2020:147:237.243. 3. Paz-Ares Let al. J Cin Oncol, 2023:11:2893-2903, PeerView.com

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10. Examining the Latest Evidence for DLL3-Targeted
T-Cell Engagers and Other Novel Therapies

Taofeek K. Owonikoko, MD, PhD
The Marlene and Stewart Greenebaum Distinguished Professor in Oncology
Executive Director of the University of Maryland's Marlene and Stewart Greenebaum

| Comprehensive Cancer Center
Senior Associate Dean of Cancer Programs, University of Maryland School of Medicine
Associate Vice President of Cancer Programs, University of Maryland, Baltimore
Baltimore, Maryland

Go online to access full CME/AAPA information, including faculty disclosures.

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11. DeLLphi-300
Efficacy of Tarlatamab in SCLC’

DeLLphi-300: Phase 1 Open-Label Dose-Escalation Study of Tarlatamab in SCLC

‘est change Frm Benen Sem ot lm.
Esbebeoreseds

Promising antitumor activity with encouraging response durability in heavily pretreated SCLC: confirmed ORR 23%,
median DOR 13 mo, median OS 13.2 mo

Acceptable safety profile: CRS primarily grade 1 and reversible; treatment discontinuation because of TRAES low (4%)

1.PazrAres etal. J Cin Oncol. 2023:41:2892-2903. PeerView.com

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12. DeLLphi-301: Tarlatamab in 23L SCLC12

Key Inclusion Criteria
ES-SCLC

platinum-doublet)
ECOG PS 0-1
Measurable disease
Treated and stable brain
metastases allowed

1. ps elias govletishowNCTOS060016, 2. Paz-AresL et al. ESMO 2023. Abstract LBA92

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Part 1: Dose Evaluation

Tarlatamab 10 m

(n= 88)

on day 1,
by 10 mg on

Part 3: Reduced
Inpatient Monitoring
Period

Part 2: Dose Expansion

Tarlatamab 10 mg Tarlatamab 10 mg
(n= 12) (n= 34)

me dosing as me dosing as

part 1 part 1

+ Primary endpoints: ORR per RECIST v1.1 by BICR, TEAES, tarlatamab
serum concentrations

+ Secondary endpoints: DOR, DCR, PFS per RECIST v1.1 by BICR, OS

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13. DeLLphi-301 Confirmed the Clinical Efficacy

| Medan followup of 10.6 months.

of Tarlatamab in SCLC1:22

rlatamab 10 mg Tarlatamab 100 mg

aus (n= 100) (n= 88)
[ORR, n (%) (97.5% CI) 40 (40) (29- 28 (32) (21-44)
CR 10) 7(8)
PR 39 (39) 21(24)
SD 30 (30) 27 (31)
PD 20 (20) 13(15)
NE/no post-baseline scan 10 (10) 20 (23)
mDOR, mo (95% Cl) NE (5.9-NE) NE (6.6-NE)
Observed DOR 26 mo, n/N (%) 23/40 (58) 17/28 (61)
DCR, n (%) (95% Cl) 70 (70) (60-79) 55 (63) (52-73)
Median PFS, mo (95% Cl) 49 (29-67) 3.9(26-44)
Median OS, mo (95% CI) 14.3 (10.8-NE) NE (12.4-NE)
IE métis subi
3 © (n=91) (n=70)
q
“a ET m
EX ie WPD Unicas
Ade
gen
2%
2 +
En
in

4: PazsAres Leta), ESMO 2023, Abstract LOAG2. 2. Ann M et al N Engl J Med. 2023:309:2069-2018.

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14. Responses Were Durable
With Both Tarlatamab Dosages‘?

Onset and Duration of Response
A First response (partial response or better) ll Disease progression > Ongoing treatment Ill Death
Tarlatamab 10 mg (n = 40) Tarlatamab 100 mg (n = 28)

Patients

0 10 2 30 40 50 © 70 8 0 10 20 30 40 50 60 70 80
Duration of Treatment, wk

1.Paz-Ares Letal. ESMO 2023. Abstract LBAS2, 2. Ann M tal N Engl J Med. 2023:380:2063-2075. PeerView.com

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15. Improved Survival Shown
With Both Tarlatamab Dosages’?

Tarlatamab Tarlatamab
10mg 100 mg
100) (n= 88)

Tarlatamab
16

joutcome in
Median OS, mo (95% CI) 143(I08NE) NE(124NE)

utcome (o

Medan PFS, mo (86% Cl) (29-67) 392644)

sn Tarttarea 10 09 ge
2
ia ee Eos eros e
Es H Bu
Tm, mo To, mo
an un
Mes à » e 2 ome ge aw
Teg a Pr “ 3 O

1.Paz-Ares Letal. ESMO 2023. Abstract LOAS2. 2. Ahn M et al. M Engl Med. 2023308 2063-2075. PeerView.com

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16. Majority of AEs Seen in DeLLphi-301 Were Tolerablet?2

Tarlatamab demonstrated a favorable safety profile, with a low rate of discontinuations due to TRAEs
Most common TRAE was CRS, which primarily occurred in cycle 1 and was mostly grade 1-2 and generally
manageable with supportive care
Discontinuation of tarlatamab due to TRAEs was low (3%)
Part1+2 Parti Part1+2 Parti Part
Tarlatamab Tarlatamab Tarlatamab
10 mg 10mg 100mg 10mg

TEAEs, n (4)

(n=99) (n=87) (n=34)
Ay gate IT #4) ED 16
Grae 23 769 6) 22065 #4 4665 169
Related to tarlatamab, any grade 89 (90) 81 (93) 29(85) o 56) 16)
Grade 23 29 (28) 29 (33) 5(15) Decreased appetite 25 (25) 38 (44) 13.88)
‚Fatal o o 13 Pyrexia 38 (38) 29 (33) 8(24)
[essa dose emapionneaicion 1409258936) —] consipaton 200 209 a
Leading to discontinuation 44) 36) o Anemia 26 (26) 22 (25) 9 (26)
Asthenia 20 (20) 2124) 1029)
HSE zo ma man
Fatigue mon van su

of tarlatamab (10 mg Q2W) with standard-of-care chemotherapy?

1.Paz-Ares Letal ESMO 2023, Abstract LBAG2. 2. Ahn Met al M Eng Med. 2023:389 2063-2075 3 tps einicalials govistudyyNCTOS740S66 PeerView.com

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17. FDA Approval of Tarlatamab’

On May 16, 2024, the FDA granted accelerated
approval to tarlatamab for ES-SCLC with disease

progression on or after platinum-based chemotherapy

1. ntps wrt. gov/srugs/tesources-nformaton-approved-drupsé-grans-accelerted-approvatiarataab-die-etensve-stage-smaltcelung-cancer PeerView.com

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18. First-in-Human Dose-Escalation Trial of Bl 764532
in Patients With SCLC or NECs!

Key Inclusion Crite

‘Advanced SCLC,
LCNEC, or epNEC.

‘DLLS positive (archived tissue
or in-study biopsy) according
to central review

Regimen B2

Failed/ineligible for available A
standard therapies (21 line Switch to B1 based ‘Switch to step-in dosing (82)
of platinum-based chemotherapy on regimen A data based on regimen A and 81 data

‘Adequate liver, bone marrow,

‚and renal function Primary Endpoints Secondary Endpoints

ECOG PS 0/1 + MID ‘+ Objective response (RECIST v1.1)
+ DLTsin the MTD evaluation period +_PK parameters

Patients are treated until disease worsening or a maximum duration of 36 months:

1. Wermke M et al, ASCO 2023. Abstract 8502. PeerView.com

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19. BI 764532: Efficacy Was Observed
Across All Enrolled Tumor Types!

Efficacy by Tumor Type (Doses 290 ug/kg)

SCLC epNEC LCNEC

27; (n
100
0) 5 (60)
£ 10(26) 728) 240)
3 1261) 1348 0
5,” 20(51) 124) 51100)
EX 7a M
Es
¿8
82 °
3
g +0

100

*Elicacypopulaon: 21 post baseline tumor assessment or permanent disconimued prior o lumor assessment. responses evaluated per RECIST v1.1 criteria,
* Discontinued prior to tumor assessment a
1. Werke Metal ASCO 2023. Abstract 8502 PeerView.com

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20. Phase 1/2 Study of HPN328 in Patients
With SCLC and Other NECs!

ind Step-Dose Cohorts and Dose Optimiza!
jeptember 2023)

‘Ongoing 1 mg priming step-dose
escalation and optimization cohorts

bi a Early fixed-dose and step-dose

"Target popultion ‘escalation cohorts

+ SCLCrelapsedirefractory after
platinum chemotherapy

+ Neuroendocrine prostate cancer
(NEPC) relapsedirefractory to SOC

+ Other high-grade neuroendocrine
neoplasms (NEN) relapsedirefractory
to SOC or no SOC available; DLL3
expression by IHC required

2m9 + zu

001530 ma

"One: mg to 24-mg cohorts use a 12:mg intermediate step-up prior o moving o 24m target. © St eroling: protocol als for cohorts of up to 17 patients,
"depending on cohort.“ Atezo combination cohorts recanty opened: dala 1 be presente at ater date $
‘Choudhury Net a. SMO 2023. Absract 699°. PeerView.com

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21. HPN328: Responses Seen Across Tumor Types
With Minimal Effective Dose’

Response in Patients Treated at 2Minimal Effective Dose (21.215 mg)

m With 21 Post-Baseline Assessment (n = 49)
+ Axis capped of.
at 100%, although E a
largest changes © 4]
were >100.0% F1
+ EC-PR= whee
extracranial partial E
response per a Hee
mRECIST 5
on

20

0 non

& ES

400

2 NEN patent envied va 0% DLL3 expression, preto protocol requirement. In patents with opportunity to have two acan or discontinued pr o contmateey

scan due to AE 01 PO. «Patents on study wih ony one imaging assessment to date. Incudes RECIST-based normalzation of mph node sie, patent achieved

CPR prior 10 CR, 30 considered a confmed response." Patent wth rain mes a week 2 Iraciatedwih continued extrcranal response fr 68 weeks a

1 Choudhury Net al. ESMO 2025, Abstract 698°. PeerView.com

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22. Tarlatamab and Other DLL3 T-Cell Engagers:

Ongoing Trials
Agent Disease Setting NCT Notes
Tarlatamab LS-SCLC; 1L maintained NCT06117774 Tarlatamab vs placebo following chemo RT

Tarlatamab ES-SCLC; 1L maintained NCTOS211036 — Tarlatamab + durvalumab vs durvalumab following EP + PD-L1
RO7616789 RIRSCLCandNECs NCTO5619744 Trispecific, including CD137 Ab

QLS31904 R/R SCLC and NECs NCTO5461287 -

BI764532 ES-SCLC; 1L maintained NCT06077500 Combo with EP + PD-L1

BI 764532 RIR SCLC NCT05990738 Combo with topotecan

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23. Applying the Latest Evidence for
DLL3-Targeted T-Cell Engagers to Clinical Practice

Taofeek K. Owonikoko, MD, PhD
The Marlene and Stewart Greenebaum Distinguished Professor in Oncology
= Executive Director of the University of Maryland's Marlene and Stewart Greenebaum
| Comprehensive Cancer Center
Senior Associate Dean of Cancer Programs, University of Maryland School of Medicine
Associate Vice President of Cancer Programs, University of Maryland, Baltimore
Baltimore, Maryland

Go online to access full CME/AAPA information, including faculty disclosures.

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24. Patient Case

A 78-year-old man newly diagnosed with ES-SCLC (ECOG PS 1) received initial treatment with EP +
durvalumab

He completed 4 cycles of induction chemoimmunotherapy with delays in initiating C3 and C4
because of delayed count recovery

He transitioned to durvalumab maintenance

Routine restaging CT scans after 2 cycles of Q4W maintenance durvalumab unfortunately
demonstrated multiple new or progressive hepatic lesions

MRI of brain shows 4 sub-centimeter parenchymal lesions consistent with metastases and
without perilesional edema

ECOG PS remains preserved, and he wants to explore other therapeutic options

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25. NCCN Guidelines: 2L+ Systemic Therapy for ES-SCLC!

SCLC Subsequent Systemic Therapy for Patients With PS 0-2)*

Chemotherapy-Free Interval >6 Months
Preferred Regimens

+ Clinical trial enrollment

+ Retreatment with platinum-based doublet

Other Recommended Regimens

+ Lurbinectedin + Irinotecan

- Topotecan PO or IV + Tarlatamab-dlle

Chemotherapy-Free Interval <6 Months

Preferred Regimens.

+ Clinical trial enrollment + Tarlatamab-dlle

+ Lurbinectedin + Retreatment with platinum-based doublet

+ Topotecan PO or IV may be considered for chemotherapy-free

+ Irinotecan interval of 3-6 mo

Other Recommended Regimens

+ Nivolumab or pembrolizumab (if not previously + Cyclophosphamide/doxorubicin/vincristine (CAV)
treated with an ICI) + Docetaxel

+ Paclitaxel + Gemcitabine

Temozolomide

Oral etoposide

* Consider dose reduction or growth factor suppot for patients wäh PS 2 ds
1.NGGN Clica Practice Guidelines in Oncology. Small Gel Lung Cancer. Version 2 2025. hips /hww.ncen orgiprotessionals/physcian_ols/pdtisle pat PeerView.com

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26. Case Discussion

+ What are the treatment options for this patient after management of brain metastases?
— Retreat with platinum/etoposide
— Topotecan
— Irinotecan

Lurbinectedin

Tarlatamab

Referral to hospice

+ Candidate selection for tarlatamab vs other therapies
— DLL3 biomarker testing is currently not required for treatment with tarlatamab

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27. Patient Case Continues

A 78-year-old man newly diagnosed with ES-SCLC (ECOG PS 1) received initial treatment with EP + durvalumab

He complete: les of induction immunotherapy with delays in initia

because of ed count recovel
te transitioned to durvalumab maintenance

ne restaging CT scans after 2 cycles of Q4W maintenance durvalumab unfortunately demonstrated
y or progressive hepatic lesions

MRI of brain shows 4 sub-centimeter parenchymal lesions consistent with metastases and
without perilesional edema

206 PS remains preserved, and he wants to explore other therapeutic options
Patient is started on tarlatamab
He develops CRS after the second dose of cycle 1

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28. CRS Presentation and Grading’

Management of AEs associated with tarlatamab ade
— Cytokine release syndrome (CRS) Grade 1
— Immune effector-associated neurotoxicity

syndrome (ICANS)
Grade 2
— Others

CRS symptoms are progressive, and can

include pyrexia, hypotension, fatigue,

tachycardia, headache, hypoxia, nausea, Grade 3

and vomiting

Potentially life-threatening complications may

include cardiac dysfunction, acute respiratory rate 4

distress syndrome, neurologic toxicity, renal
and/or hepatic failure, and disseminated
intravascular coagulation (DIC)

Defining Symptoms

‘Symptoms require symptomatic treatment only
(69, fever =100.4°F without hypotension or hypoxia)

‘Symptoms require and respond to moderate intervention

+ Fever 2100.4°F

+ Hypotension responsive to fuids not requiring vasopreseors
AND/OR

+ Hypoxia requiring low-flow nasal cannula or blow-by

‘Severe symptoms defined as temperature =100.4°F with:

+ Hemodynamic instabilty requiring a vasopressor (with or
‘without vasopressin) OR

+ Worsening hypoxia or respiratory distress requiring high-low
nasal cannula (>8 Limin oxygen) or face mask

Lite-threatening symptoms defined as temperature 2100.4*F

wth

+ Hemodynamic instabilty requiring muliple vasopressors.
(excluding vasopressin)

+ Worsening hypoxia or respiratory distress despite oxygen
administration requiring positive pressure

1. Lee DW et al Bio Blood Marrow Transplant. 2019:25:625-638. 2. Imdelta(taratamab) Prescrbin Information.

histo accessdata fda govidrugsatida_docs/abel2024/761344s0001 pat. PeerView.com

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29. Tarlatamab: CRS Management Recommendations"

‘Administer tarlatamab according to the

step-up dosing schedule to reduce CRS.

incidence and severity

+ Monitor patients from start of tarlatamab
infusion for 22-24 h on cycle 1 days 1 and 8
in an appropriate healthcare setting

+ Diagnose CRS based on clinical
presentation

+ Evaluate for and treat other causes of fever,
hypoxia, and hypotension

+ IFORS is suspected, manage according to
the recommendations in the table

+ Monitor patients who experience grade 22
CRS with continuous cardiac telemetry and
pulse oximetry; perform laboratory testing
to monitor for DIC and hematology
parameters, as well as pulmonary, cardiac,
renal, and hepatic function

+ For severe or life-threatening CRS,
recommend tocilizumab or equivalent
therapy and admission in ICU for
supportive therapy

Dosage Modifications

‘Wihholdtartatamab unt event

resolves, then resume tarlatamab
‘at the nex! scheduled dose

Wihnold tarlatamab until event
resolves, then resume talatamab
atthe next scheduled dose

+ Wnholdtartatamab until event
resolves, then resume taratama
at the next scheduled dose

+ For recurrent grade 3 events,
permanent} discontinue
tarlatamab

Permanently discontinue
tarlatama

Management Strategies

Administer symptomatic treatment (eg, acetaminophen) for fever

+ Recommend hospitalization for 224 h with cardiac telemetry and
puse oximetry
+ Administer symptomatic treatment (eg, acetaminophen) for fever
+ Administer supplemental oxygen and IV fluids when indicated
+ Consider dexamethasone (or equivalent) 8 mg IV
+ Consider toctizumab (or equivalent)
When resuming treatment atthe next planned dose, monitor
patients from the start of infusion for 22-24 h in an appropriate
healthcare setting
In addition to grade 2 treatment:
+ Recommend intensive monitoring (eg, ICU care)
+ Administer dexamethasone (or equivalent) 8 mg IV every 8 h up
Lo 3 doses
+ Vasopressor support as needed
+ Hgh-fow oxygen support as needed
+ Recommend toclizuma (or equivalent)
+ Prior to the next dose, administer concomitant medications as
recommended for cycle 1
‘When resuming treatment at ne next planned dose, monitor
patients from the star of infusion for 22-24 h in an appropriate
healthcare setting
+ ¡CU care
+ Per grade 3 treatment
- Recommend toclizumab (or equivalent)

1. Lee DW et al io Blood Marrow Transplant. 2019:25.625:638. 2. dela (Lt ab) Presenbing Information,

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30. + ICANS may occur in the
CNS following treatment
with T-cell-engaging
therapies as a result of
activation or engagement
of endogenous or infused
T cells and/or other
immune effector cells

+ Onset of ICANS can be
concurrent with, following
resolution of, or in the
absence of CRS.

+ Clinical signs and
symptoms of ICANS can
include confusional state,
depressed level of
consciousness,
disorientation,
somnolence, lethargy,
and bradyphrenia

2 Based on ASTCT Consensus Grading (2018)

Grading ICAN:

+ ICE score 7-9 with no depressed level of consciousness

+ ICE score 3-6 AND/OR
+ Mild somnolence awakening to voice
+ ICE score 0-2 AND/OR

+ Depressed level of consciousness awakening only to

tactile stimulus AND/OR

+ Any clinical seizure, focal or generalized, that resolves
rapidly or nonconvulsive seizures on EEG that resolve

with intervention AND/OR
+ Focal or local edema on neuroimaging

+ ICE score 0 (patient is unarousable and unable to

perform ICE) AND/OR
+ Stupor or coma AND/OR

+ Life-threatening prolonged seizure (>5 min) or repetitive
clinical or electrical seizures without return to baseline

in between AND/OR

+ Diffuse cerebral edema on neuroimaging, decerebrate

or decorticate posturing or papilledema,
cranial nerve VI palsy. or Cushing's triad

1. Lee DW et al Bio Blood Marrow Transplant. 2019:25 625-638. 2. delta (taratamab) Prescrbin Information.
hist accessdata fda goVidrugsatida_docs/abel2024/761344s0001 pat.

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ICANS Presentation and Grading’?

immune Effector Cell-Associated

Encephalopathy (ICE) Assessment Tool
‘Assessment Points.

Orientation: orientation

to year, month, city, 4
hospital

Naming: ability to name

3 objects (eg, point to 3

clock, pen, button)

Following commands:

ability to follow simple
commands (eg, “Show 1
me 2 fingers" or “Close

your eyes and stick out

your tongue")

‘Writing: ability to write a
standard sentence (eg, A
“Our national bird is

the bald eagle")

Attention: ability to

count backwards from 1

100 by 10

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31. Tarlatamab: ICANS Management Recommendations’?

- At the frst sign of Tarlatamab Dosage Modification nagement Strategie
neurologie toxicity, ‘Withnold unt ICANS resolves, then
inching IGANS withhold” resume at the next scheduled dose Supportive care

‘Supportive care
Dexamethasone (or equivalent) 10 mg IV; can repeat every 6
h or methylprednisolone 1 mg/kg IV every 12 h if symptoms

tarlatamab and consider
neurology evaluation

* Closely monitor patients for Withhold until ICANS resolves, then worsen
signs and symptoms of resume at the next scheduled dose + Monitor neurologic symptoms, and consider consultation with
neurologic toxicity and neurologist and other specialists for further evaluation and
ICANS during treatment management

+ Monitor for 22-24 h following the next tarlatamab dose
Recommend intensive monitoring (eg, ICU care)
Consider mechanical ventilation for airway protection

+ Rule out other causes of
neurologic symptoms

+ Withhold until ICANS resolves, then
resume at the next scheduled dose

+ Provide supportive therapy, + Ifno improvement to grade <1 within 7 + Dexamethasone (or equivalent) 10 mg IV every 6 h or
including intensive care, 3 d'or grade 3 toxicity reoccurs within 7d methylprednisolone 1 mg/kg IV every 12h
for severe or life- of re-intiation, permanently discontinue + Consider repeat neuroimaging (CT or MRI every 2-3 dif
threatening neurologic + For recurrent grade 3 events, patient has persistent grade 23 neurotoxicity
toxicities, including ICANS permanently discontinue. + Monitor for 22-24 h following the next tarlatamab dose

ICU care
Consider mechanical ventilation for airway protection
High-dose corticosteroids

Consider repeat neuroimaging (CT or MRI) every 2-3 d if
patient has persistent grade 23 neurotoxicity

+ Manage ICANS and
neurologic toxicity
according to the 4 Permanently discontinue
recommendations in

the table + Treat convulsive status epilepticus per institutional guidelines
1.Lee OW et al Bio! Blood Marrow Transplant 2019,25625608, 2 dela aratamab) Prescning Inormaton =
ps ww accessdata da govlerugsatida_docslabel/2024/76 1344500001 pat. PeerView.com

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