Making Precision Decisions for Patients With EGFRm NSCLC: Success Strategies With Targeted Options, Potent Combinations, and Emerging Agents
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About This Presentation
Co-Chairs, Prof. Nicolas Girard, MD, PhD, and Pasi A. Jänne, MD, PhD, discuss NSCLC in this CME/MOC/NCPD/AAPA/IPCE activity titled “Making Precision Decisions for Patients With EGFRm NSCLC: Success Strategies With Targeted Options, Potent Combinations, and Emerging Agents.” For the full present...
Slide Content
Making Precision Decisions for Patients
With EGFR-Mutated NSCLC
Success Strategies With Targeted Options, Potent
Combinations, and Emerging Agents
Pasi A. Jänne, MD, PhD + Nicolas Girard, MD, PhD
Senior Vice President for Translational ho Professor of Respiratory Medicine
Medicine Versailles Saint Quentin University
Director, Belfer Center for Applied Paris Saclay University
Cancer Science Chair, Department of Medical Oncology
Dana-Farber Cancer Institute Thoracic Oncologist
Director, Chen-Huang Center for Institut Curie
EGFR Mutant Lung Cancers Paris, France
Professor of Medicine, Harvard
Medical School
Boston, Massachusetts
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2025, PeerView
With EGFR-Mutated NSCLC
Success Strategies With Targeted Options, Potent
Combinations, and Emerging Agents
Pasi A. Jänne, MD, PhD + Nicolas Girard, MD, PhD
Senior Vice President for Translational ho Professor of Respiratory Medicine
Medicine Versailles Saint Quentin University
Director, Belfer Center for Applied Paris Saclay University
Cancer Science Chair, Department of Medical Oncology
Dana-Farber Cancer Institute Thoracic Oncologist
Director, Chen-Huang Center for Institut Curie
EGFR Mutant Lung Cancers Paris, France
Professor of Medicine, Harvard
Medical School
Boston, Massachusetts
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2025, PeerView
Our Goals for Today
Augment your knowledge of the latest evidence supporting
the use of different EGFR-targeted therapies and combinations
in EGFR-mutated NSCLC
Equip you with skills for selection and sequencing of
established and emerging therapies and combinations in
EGFR-mutated NSCLC
Copyright © 2000-2025, PeerView
Augment your knowledge of the latest evidence supporting
the use of different EGFR-targeted therapies and combinations
in EGFR-mutated NSCLC
Equip you with skills for selection and sequencing of
established and emerging therapies and combinations in
EGFR-mutated NSCLC
Copyright © 2000-2025, PeerView
Laying the Foundation for Precision Medicine in
EGFR-Mutated NSCLC
Real-World Barriers in Testing and Treatment
Copyright © 2000-2025, PeerView
EGFR-Mutated NSCLC
Real-World Barriers in Testing and Treatment
Copyright © 2000-2025, PeerView
Necessary Biomarker Testing in Lung Cancer: EGFR and Beyond
Different Subtypes of EGFR Mutations Prevalence Rates of EGFR Mutations
Across Different Stages of NSCLC13
E EGFR Mutations,
% (95% CI)
1 20 (19.0-20.4)
u 18 (14.9-19.9)
u 18 (17.4-17.7)
w
Comprehensive biomarker testing prior to therapy is
Other
(G719x, L861Q,. needed to optimize care
exon 19
insertions) + All targetable genomic alterations, PD-L1 expression
aR + Guides therapy in advanced and early disease
Exon 20. 40%) + Type of testing matters (tissue/blood, NGS—DNA/RNA)
10%) Accurate interpretation and application of results is essential
1. Sho Leta 4 Three Oncol 2015 10.788.772, Angle SP et oJ Thre Ono! 20127.1815822.3.Jrdn etai CancerDisor.20r7zseeane, Peer View
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Different Subtypes of EGFR Mutations Prevalence Rates of EGFR Mutations
Across Different Stages of NSCLC13
E EGFR Mutations,
% (95% CI)
1 20 (19.0-20.4)
u 18 (14.9-19.9)
u 18 (17.4-17.7)
w
Comprehensive biomarker testing prior to therapy is
Other
(G719x, L861Q,. needed to optimize care
exon 19
insertions) + All targetable genomic alterations, PD-L1 expression
aR + Guides therapy in advanced and early disease
Exon 20. 40%) + Type of testing matters (tissue/blood, NGS—DNA/RNA)
10%) Accurate interpretation and application of results is essential
1. Sho Leta 4 Three Oncol 2015 10.788.772, Angle SP et oJ Thre Ono! 20127.1815822.3.Jrdn etai CancerDisor.20r7zseeane, Peer View
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Gaps in Testing Remain in Advanced NSCLC: MYLUNG Study!
Availability of Biomarker Testing Results Patients in Advanced Cohort (N = 582) With Any
Before 1L Treatment: Biomarker Testing Results Prior to 1L Treatment
(N= 461)
Bx 60
ZE 54.6 ALK test, n (%)> 355 (77.0)
35
Es 50 BRAF test, n (9%)? 335 (72.7)
3 & a5 EGFR test, n (%)? 371 (80.5)
Pe 37
33 KRAS test, n (%)* 294 (63.8)
ef su MET test, n (96)? 328 (71.1)
El
a2 „ NTRK test, n (RP 253 (54.9)
ES
si PD-L1 est, n (MP 388 (842)
23 10
5 RET test, n (%)? 305 (66.2)
E
ao 0 CEN] TA ROS test, n (%)° 344 (74.6)
2018-2020 2020-2022
Denomimaor Protocol 2474; protocol 2, N = 555. *Denominator: patents wth biomarker esting resus prieto AL eatment .
“RAS testing is approved or itr.ine estiment. PeerView
1. Evangelst Metal ASCO 2023, Abstract 9109,
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Availability of Biomarker Testing Results Patients in Advanced Cohort (N = 582) With Any
Before 1L Treatment: Biomarker Testing Results Prior to 1L Treatment
(N= 461)
Bx 60
ZE 54.6 ALK test, n (%)> 355 (77.0)
35
Es 50 BRAF test, n (9%)? 335 (72.7)
3 & a5 EGFR test, n (%)? 371 (80.5)
Pe 37
33 KRAS test, n (%)* 294 (63.8)
ef su MET test, n (96)? 328 (71.1)
El
a2 „ NTRK test, n (RP 253 (54.9)
ES
si PD-L1 est, n (MP 388 (842)
23 10
5 RET test, n (%)? 305 (66.2)
E
ao 0 CEN] TA ROS test, n (%)° 344 (74.6)
2018-2020 2020-2022
Denomimaor Protocol 2474; protocol 2, N = 555. *Denominator: patents wth biomarker esting resus prieto AL eatment .
“RAS testing is approved or itr.ine estiment. PeerView
1. Evangelst Metal ASCO 2023, Abstract 9109,
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Substantial Gaps in Testing Also Exist in Early-Stage NSCLC:
MYLUNG Study!
Rates of Biomarker Testing in Early-Stage NSCLC
Es 210
E 70 172
3
o (62) 153 (606) 154
2
5 50
E 40
32
@ 20
5
1
dE
2 PDL1 EGFR AUK PDLI+ PDLI+
EGFR EGFR + ALK
Total tested Results <12 wk after first systemic therapy
+ Positivity rates: PD-L1 = 48%; EGFR = 17%; ALK = 3%
NGS Testing Conducted
in Half of All Patients With Early-Stage NSCLC.
No NGS
testing
No therapy received
NGS testing ordered
>12 wk after first
NGS
temic th
ey systemic therapy
ordered DY NGS testing ordered
n= 144 512 wk after first
(60.7%) systemic therapy
+ Most common reasons for not testing were patient and/or provider attitude/perception (34%) and insufficient tumor
tissue (25%)
1. Evangelst MC etal, ASCO 2024, Abstract 8047,
PeerView.com/EVZ827
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MYLUNG Study!
Rates of Biomarker Testing in Early-Stage NSCLC
Es 210
E 70 172
3
o (62) 153 (606) 154
2
5 50
E 40
32
@ 20
5
1
dE
2 PDL1 EGFR AUK PDLI+ PDLI+
EGFR EGFR + ALK
Total tested Results <12 wk after first systemic therapy
+ Positivity rates: PD-L1 = 48%; EGFR = 17%; ALK = 3%
NGS Testing Conducted
in Half of All Patients With Early-Stage NSCLC.
No NGS
testing
No therapy received
NGS testing ordered
>12 wk after first
NGS
temic th
ey systemic therapy
ordered DY NGS testing ordered
n= 144 512 wk after first
(60.7%) systemic therapy
+ Most common reasons for not testing were patient and/or provider attitude/perception (34%) and insufficient tumor
tissue (25%)
1. Evangelst MC etal, ASCO 2024, Abstract 8047,
PeerView.com/EVZ827
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Right Choice of Therapy Matters: Lack of lO Benefit in Patients
With EGFR Mutations From the PACIFIC Trial!
Median PFS (95% Cl) Median OS (95% Cl)
10 Durvalumab 11.2(7.3-20.7) Durvalumab 46.8 (29.9-NE)
19
Placebo 43 (14.9-NE)
os
se Placebo SINE) 09
HRG5% CH 102(030-26)
3 07 HR (5% CI) 0.91 (0.39-2.13) 8 rn ee
30 si
5 .
Bo Bos
po Bos
02
ES Bos
Durvalumab
= mia, Bee
01 os
o o
TU CC RGR OHH Oo 13 © o 42167001 24273059900042 50051557 C0GSSCOTETS
Time From Randomization, mo un
Time From Randomization, mo
No. at isk No. at isk
Moan 0 à 6 9 12 16 18 21 26 27 30 99 36 40 42 45 48 080 O 21staztz¢arsossanaocousansis4s7e0e3ee087275
Dunaumad 24 2 19 15 10 6 0 2 3 2 2 21 1 1 1 1 1 0 Dunmlunab AMBER DNI Ii eseztte
Pate Ne SS ea S22 E7211 1 000 oman NnOweeeTTT IESG ead ses 21000
PFS and OS outcomes with durvalumab were similar to placebo for patients with EGFRm tumors, with wide Cls
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1. Naidoo Jet al. J Thorac Oncol. 2023.18 857-683.
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With EGFR Mutations From the PACIFIC Trial!
Median PFS (95% Cl) Median OS (95% Cl)
10 Durvalumab 11.2(7.3-20.7) Durvalumab 46.8 (29.9-NE)
19
Placebo 43 (14.9-NE)
os
se Placebo SINE) 09
HRG5% CH 102(030-26)
3 07 HR (5% CI) 0.91 (0.39-2.13) 8 rn ee
30 si
5 .
Bo Bos
po Bos
02
ES Bos
Durvalumab
= mia, Bee
01 os
o o
TU CC RGR OHH Oo 13 © o 42167001 24273059900042 50051557 C0GSSCOTETS
Time From Randomization, mo un
Time From Randomization, mo
No. at isk No. at isk
Moan 0 à 6 9 12 16 18 21 26 27 30 99 36 40 42 45 48 080 O 21staztz¢arsossanaocousansis4s7e0e3ee087275
Dunaumad 24 2 19 15 10 6 0 2 3 2 2 21 1 1 1 1 1 0 Dunmlunab AMBER DNI Ii eseztte
Pate Ne SS ea S22 E7211 1 000 oman NnOweeeTTT IESG ead ses 21000
PFS and OS outcomes with durvalumab were similar to placebo for patients with EGFRm tumors, with wide Cls
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1. Naidoo Jet al. J Thorac Oncol. 2023.18 857-683.
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Dissecting the Evidence to Inform Personalized 1L
Therapy for EGFR-Mutated Advanced/Metastatic
NSCLC
Therapy for EGFR-Mutated Advanced/Metastatic
NSCLC
asing Complexity of 1L EGFR. eted Therapy Options for
FRm mNSCLC: NCCN Guidelines!
NGS-based broad molecular profiling (preferred)
EGFR mutation
EGFR exon 19 deletion
or exon 21 L858R mutation
Preferred/Recommended
+ Osimertinib (category 1)
+ Amivantamab + lazertinib* (category 1)
+ Osimertinib + pemetrexed + (cisplatin or
carboplatin) (nonsquamous) (category 1)
Useful in Certain Circumstances
Afatinib (category 1)
Dacomitinib (category 1)
Erlotinib® (category 1)
Erlotinib + ramucirumab?
Erlotinib + bevacizumab
Gefitinib? (category 1)
FDA approved. © Please consult NCCN Guidelnes fr deta on systemic therapy options. PeerView
1. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cel Lung Cancer. Version 8.2025. ps. een org professionals physican_ghpdtinse pat
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
FRm mNSCLC: NCCN Guidelines!
NGS-based broad molecular profiling (preferred)
EGFR mutation
EGFR exon 19 deletion
or exon 21 L858R mutation
Preferred/Recommended
+ Osimertinib (category 1)
+ Amivantamab + lazertinib* (category 1)
+ Osimertinib + pemetrexed + (cisplatin or
carboplatin) (nonsquamous) (category 1)
Useful in Certain Circumstances
Afatinib (category 1)
Dacomitinib (category 1)
Erlotinib® (category 1)
Erlotinib + ramucirumab?
Erlotinib + bevacizumab
Gefitinib? (category 1)
FDA approved. © Please consult NCCN Guidelnes fr deta on systemic therapy options. PeerView
1. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cel Lung Cancer. Version 8.2025. ps. een org professionals physican_ghpdtinse pat
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
FLAURA: Phase 3 Study of 1L Osimertinib in
EGFRm Advanced/Metastatic NSCLC?
MOS, mo (95% Cl)
Best Change From Baseline os TT ETT
in Target Lesions 10: Comparator EGFR TKI___318 (26 6-36 0)
Osimertinib =
Qsimertinib
Comparator EGFR TKI
or] HR= 0.80 (05.05% 01.064.100)
Pa 066
ol
OS 6 8 1215 v0 1 4 OF 50 95 50 50 2 a RE
ovata Time Since Randomization, mo
EEE
mPFS = 18.9 mo
Improved intracranial penetration vs 1G TKIs
Gefitinib or Erlotinib
Toxicities: rash, diarrhea, paronychia (low
grade), QTc prolongation, and ILD (rare)
1. Sara JC tal. Eng Med. 2018378:113-125 2, Ramaingam SS «tl. Engl J Med. 20202824150, PeerView
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EGFRm Advanced/Metastatic NSCLC?
MOS, mo (95% Cl)
Best Change From Baseline os TT ETT
in Target Lesions 10: Comparator EGFR TKI___318 (26 6-36 0)
Osimertinib =
Qsimertinib
Comparator EGFR TKI
or] HR= 0.80 (05.05% 01.064.100)
Pa 066
ol
OS 6 8 1215 v0 1 4 OF 50 95 50 50 2 a RE
ovata Time Since Randomization, mo
EEE
mPFS = 18.9 mo
Improved intracranial penetration vs 1G TKIs
Gefitinib or Erlotinib
Toxicities: rash, diarrhea, paronychia (low
grade), QTc prolongation, and ILD (rare)
1. Sara JC tal. Eng Med. 2018378:113-125 2, Ramaingam SS «tl. Engl J Med. 20202824150, PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
FLAURA2: Phase 3 1L Osimertinib + Chemo Significa
y
Improved PFS vs Osimertinib Alone in EGFRm NSCLC14
PFS per Investigator Assessment
Median PFS, mo
(95% Cl)
Osimertinib + chemo 25.5 (24.7-NC)
Osimertinib 16.7 (14.1-21.3)
HR (85% CI) 0.62 (0.49-0.79)
<.0001
Osimertinib + chemo
Osimertinib
0 3 6 6 12 15 0 À 2% 2 3% 33 36
Time Since Randomization, mo
No. at Risk
Omen 79 254 241 225 207 187 165 133 8 42 21 3 0
Osmertnb278 246 227 203 178 148 119 94 67 48 21 1 0
(Data eutft Ap 3, 2023.
1. Janne P et al. WLC 2023, Abstract PLOS.13. 2, Planchard D etal ESMO 2023. Abstract LBAGS. 3. Planchard D et al Eng! J Med. 2023:389:1995-1948. PeerView
4 Valdviezo N et al. Ann Oncol, 2024.9:1-53,
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y
Improved PFS vs Osimertinib Alone in EGFRm NSCLC14
PFS per Investigator Assessment
Median PFS, mo
(95% Cl)
Osimertinib + chemo 25.5 (24.7-NC)
Osimertinib 16.7 (14.1-21.3)
HR (85% CI) 0.62 (0.49-0.79)
<.0001
Osimertinib + chemo
Osimertinib
0 3 6 6 12 15 0 À 2% 2 3% 33 36
Time Since Randomization, mo
No. at Risk
Omen 79 254 241 225 207 187 165 133 8 42 21 3 0
Osmertnb278 246 227 203 178 148 119 94 67 48 21 1 0
(Data eutft Ap 3, 2023.
1. Janne P et al. WLC 2023, Abstract PLOS.13. 2, Planchard D etal ESMO 2023. Abstract LBAGS. 3. Planchard D et al Eng! J Med. 2023:389:1995-1948. PeerView
4 Valdviezo N et al. Ann Oncol, 2024.9:1-53,
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FLAURA2: 1L Osimertinib + Chemo Showed Superior OS vs
Osimertinib in EGFRm mNSCLC!
Events/Patients, n (%) Median O:
‘Osimertinib + chemotherapy 1447278 (52) 47.5 (41.0-NC)
Osimerinib 171/278 (62) 37.6(832432)
#0) 2years HR (95% Cl) 0.77 (061-098)
an ? =
08 3 years.
8 ! 63%
Sos 1 years Osimertinio +
2 1 49% chemotherapy
5 1
3 1 1
204 1 1
3 É h 41% y
& 1 1 1
02 Median follow-up (censored patents), mo (range): ! !
‘Osimertnib + chemotherapy, 51.2 (0.2-60.4) | H ı
Osimertinib, 51.3 (0.1-60.1) 1 1 1
00 + + +
0 3 6 9 12 15 18 21 24 27 3 33 36 39 42 45 48 51 54 57 60 63
Time From Randomization, mo
A M0 MI 2 MS Stk ww
1. Panchad D ta CLE 2025. Abstract PLOZ4 PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Osimertinib in EGFRm mNSCLC!
Events/Patients, n (%) Median O:
‘Osimertinib + chemotherapy 1447278 (52) 47.5 (41.0-NC)
Osimerinib 171/278 (62) 37.6(832432)
#0) 2years HR (95% Cl) 0.77 (061-098)
an ? =
08 3 years.
8 ! 63%
Sos 1 years Osimertinio +
2 1 49% chemotherapy
5 1
3 1 1
204 1 1
3 É h 41% y
& 1 1 1
02 Median follow-up (censored patents), mo (range): ! !
‘Osimertnib + chemotherapy, 51.2 (0.2-60.4) | H ı
Osimertinib, 51.3 (0.1-60.1) 1 1 1
00 + + +
0 3 6 9 12 15 18 21 24 27 3 33 36 39 42 45 48 51 54 57 60 63
Time From Randomization, mo
A M0 MI 2 MS Stk ww
1. Panchad D ta CLE 2025. Abstract PLOZ4 PeerView
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Osimertinib + Chemo Showed PFS Benefit in Patients or Without Liver or Bone
Metastases at Baseline vs Osimerti Alone
With Liver Metastases Without Liver Metastases
mPi
mer + cnemotnerapy 278 (24.7 NC)
Came + chemoinerapy 195 (115249)
En Bio Qsimerini 19.4 (15.4250)
208 HR (65% Gi) 2088 41-107) 30 HR GEN G)= 063048083)
Es En
Osimertin +
ge smart schoen À 02 css
ES En
EEE RETA os eeu we oe
fae Time From Randomization, mo ee Time From Randomization, mo
With Bone Metastases. Without Bone Metastases.
Em emo) 210 (ZZNO) Bio marin ehemenerany
Bos 30
EN TR HNO) 068 (040077) 3%
E Gamer + ê
0. chemotherapy ries
Boz aimee Loo aes
o °
DE 2 8 mo ITA a de
aes ‘Time From Randomization, mo Baar Time From Randomization, mo
PeerView
Y Valgwiezo N et al. WCLG 2024. Abstract MAT2.04
PeerView.com/EVZ827 Copyright © 2000-2025, Peerview
Metastases at Baseline vs Osimerti Alone
With Liver Metastases Without Liver Metastases
mPi
mer + cnemotnerapy 278 (24.7 NC)
Came + chemoinerapy 195 (115249)
En Bio Qsimerini 19.4 (15.4250)
208 HR (65% Gi) 2088 41-107) 30 HR GEN G)= 063048083)
Es En
Osimertin +
ge smart schoen À 02 css
ES En
EEE RETA os eeu we oe
fae Time From Randomization, mo ee Time From Randomization, mo
With Bone Metastases. Without Bone Metastases.
Em emo) 210 (ZZNO) Bio marin ehemenerany
Bos 30
EN TR HNO) 068 (040077) 3%
E Gamer + ê
0. chemotherapy ries
Boz aimee Loo aes
o °
DE 2 8 mo ITA a de
aes ‘Time From Randomization, mo Baar Time From Randomization, mo
PeerView
Y Valgwiezo N et al. WCLG 2024. Abstract MAT2.04
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FLAURA2: 1L Osimertinib + Chemo Improved PFS vs
Osimertinib Alone in EGFRm NSCLC With CNS Metastases’
With CNS Metastases Without CNS Metastases
EES
Osimertinib + chemo 24.9 (22.0-NC) Osimertinib+ chemo 27.6 (24.7-NC)
Osimertinib 43.8 (11.0-16.7) Osimertinib 21 (16.7-30 5)
HR = 0.47 (95% Cl, 0.33-0.66) HR = 0.75 (95% Cl, 0.55-1.03)
10
z
3 Osimertinib + 309 Osimertinib +
gos chemo gos chemo
=“ 54 Osimertinib
402 £02
004 00
0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 6 9 12 15 18 21 24 27 30 33 36
Time From Randomization, mo Time From Randomization, mo
No. stick Norsk
wu man MT 7 % M 0 » 2 0 DE us we 1 10 0 7 & 2 1 1 0
Se” mann 7 mo 1 5 1 0 mes de ee
1. Valdez Neta. WCLC 2024 Abstract A12.04 PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Osimertinib Alone in EGFRm NSCLC With CNS Metastases’
With CNS Metastases Without CNS Metastases
EES
Osimertinib + chemo 24.9 (22.0-NC) Osimertinib+ chemo 27.6 (24.7-NC)
Osimertinib 43.8 (11.0-16.7) Osimertinib 21 (16.7-30 5)
HR = 0.47 (95% Cl, 0.33-0.66) HR = 0.75 (95% Cl, 0.55-1.03)
10
z
3 Osimertinib + 309 Osimertinib +
gos chemo gos chemo
=“ 54 Osimertinib
402 £02
004 00
0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 6 9 12 15 18 21 24 27 30 33 36
Time From Randomization, mo Time From Randomization, mo
No. stick Norsk
wu man MT 7 % M 0 » 2 0 DE us we 1 10 0 7 & 2 1 1 0
Se” mann 7 mo 1 5 1 0 mes de ee
1. Valdez Neta. WCLC 2024 Abstract A12.04 PeerView
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FLAURA2: 1L Osimertinib + Chemo Showed a High Proportion of
CRs in the CNS (by CNS BICR) in EGFRm mNSCLC!
Osimertinib + Platinum-Pemetrexed Osimertinib
(cEFR; n= 382) (cEFR; n = 38)
a
go
Do Median best change from baseine go Median best change from baseline
Es In CNS target lesion size % in CNS target sion sze, %:
Ego -94 (range, -100 to 7) -61 (range, -100 to 68)
20 pS |
go
$2 0
58%
ge
do.
E
EX CEFR (n= 78)
Measurable + Nonmea: Measurable BM
ge eee A Osimertinib ‘Osimertinib + Chemo ‘Osimertinib
(n= 104) (n= 40) 8)
‘CNS ORR (95% Cl), % 73 (64.0-81.0) 69 (690-780) 88 (73.0-96.0) 87 (72.0-96.0)
‘Complete response, n (%) 70 (69) 45 (43) 19 (48) 6 (16)
Partial response, n (%) 16(14) 27 (26) 16 (40) m
CNS DCR (95% Cl), % 91 (840-250) 3 (87.0.97.0) 95 (83.0-99.0) 97 (@6.0-100.0)
Median DoR (95% Ci}, mo NR (23.8:NO) 282 (194-NC) NR (21.6-NC) 209 (12.6-N0)
Bor:
WOR
PR
ms
meo
NE
R Prior ONS
radiotherapy?
2 Two patents had 21 measurable CNS lesion at bassin by CNS BICR bu ied before the olow-up CNS BICR scan. © In he eEFR, 440 patents (10%) nthe mer + platnum-
pemetexed arm and 7138 patins (18%) inthe camerino arm had race prior CNS radiharapy, sable reuciogcl sas lr 22 wk aer carlton of dtritve eaten and loción
Mra edures foo study ey. acen Responses e ot require conmaton, par RECIST gudance on randomized suchen, Kaplan ir emater PeerVi
eerView
4. Planchard D et al ESMO 2023, Abstract LBASS.
PeerView.com/EVZ827
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CRs in the CNS (by CNS BICR) in EGFRm mNSCLC!
Osimertinib + Platinum-Pemetrexed Osimertinib
(cEFR; n= 382) (cEFR; n = 38)
a
go
Do Median best change from baseine go Median best change from baseline
Es In CNS target lesion size % in CNS target sion sze, %:
Ego -94 (range, -100 to 7) -61 (range, -100 to 68)
20 pS |
go
$2 0
58%
ge
do.
E
EX CEFR (n= 78)
Measurable + Nonmea: Measurable BM
ge eee A Osimertinib ‘Osimertinib + Chemo ‘Osimertinib
(n= 104) (n= 40) 8)
‘CNS ORR (95% Cl), % 73 (64.0-81.0) 69 (690-780) 88 (73.0-96.0) 87 (72.0-96.0)
‘Complete response, n (%) 70 (69) 45 (43) 19 (48) 6 (16)
Partial response, n (%) 16(14) 27 (26) 16 (40) m
CNS DCR (95% Cl), % 91 (840-250) 3 (87.0.97.0) 95 (83.0-99.0) 97 (@6.0-100.0)
Median DoR (95% Ci}, mo NR (23.8:NO) 282 (194-NC) NR (21.6-NC) 209 (12.6-N0)
Bor:
WOR
PR
ms
meo
NE
R Prior ONS
radiotherapy?
2 Two patents had 21 measurable CNS lesion at bassin by CNS BICR bu ied before the olow-up CNS BICR scan. © In he eEFR, 440 patents (10%) nthe mer + platnum-
pemetexed arm and 7138 patins (18%) inthe camerino arm had race prior CNS radiharapy, sable reuciogcl sas lr 22 wk aer carlton of dtritve eaten and loción
Mra edures foo study ey. acen Responses e ot require conmaton, par RECIST gudance on randomized suchen, Kaplan ir emater PeerVi
eerView
4. Planchard D et al ESMO 2023, Abstract LBASS.
PeerView.com/EVZ827
Copyright © 2000-2025, PeerView
FLAURA2: TP53 Alterations May Be Prognostic for PFS Benefit
With Osimertinib + Chemo Over Osimertinib Alone!
TP53 Wild Type at Baseline TP53 Altered at Baseline
mPFS, mo (95% Ci)
Osimerinib + chemotherapy (n= 31) NR (24.7-NC) Osimertinb + chemotherapy (n= 41) 27.6 (24.7-NC)
Osimertinib (n = 31) NR(NC-NC) Osimertinib (n = 38) 27.6 (13.9-30.3)
HR = NC HR = 0.57 (95% Cl, 0.29-1.12)
zt 2
Bor Osimertnib+ 2 Canalis
El Osimertinib chemotherapy El chemotherapy
Eos €
» ©
£ 0% 1 Osimerinib
o
As en ee %
tes. ai ta Time From Randomization, mo dei Time From Randomization, mo
Gumernbs sy 2 2 2 0 1 0 Obs ss 2% M 4
MS 2% M 1 "à 0 Gimme 2% 4m 1 © 5 o
1. Yang JC ell. WOLO 2024 Abstract MA 12.02 PeerView
PeerView.com/EVZ827
Copyright © 2000-2025, PeerView
With Osimertinib + Chemo Over Osimertinib Alone!
TP53 Wild Type at Baseline TP53 Altered at Baseline
mPFS, mo (95% Ci)
Osimerinib + chemotherapy (n= 31) NR (24.7-NC) Osimertinb + chemotherapy (n= 41) 27.6 (24.7-NC)
Osimertinib (n = 31) NR(NC-NC) Osimertinib (n = 38) 27.6 (13.9-30.3)
HR = NC HR = 0.57 (95% Cl, 0.29-1.12)
zt 2
Bor Osimertnib+ 2 Canalis
El Osimertinib chemotherapy El chemotherapy
Eos €
» ©
£ 0% 1 Osimerinib
o
As en ee %
tes. ai ta Time From Randomization, mo dei Time From Randomization, mo
Gumernbs sy 2 2 2 0 1 0 Obs ss 2% M 4
MS 2% M 1 "à 0 Gimme 2% 4m 1 © 5 o
1. Yang JC ell. WOLO 2024 Abstract MA 12.02 PeerView
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Copyright © 2000-2025, PeerView
FLAURA2: Baseline Plasma EGFR Mutation May Predict Greater
Clinical Benefit With Osimertinib + Chemo vs Osimertinib Alone’
Patients With Baseline Detected
Plasma EGFR Mutation
iients With Baseline Nondetected
Plasma EGFR Mutation
"Oumar + cheneterary 333 SENG)
Suman women Los orne agen
Osmertnib +
Los Osimertinio + chemotherapy
» chemotherapy oe
Los Osimertn’s Lo2 osmertni
o LR 2060 (05% 01. 04500) y [HR 085 (95% 01.081172
8 6 Rn m à 3 De
Time From Randomization, mo Time From Randomization, mo
fio sek No. at oe
ESS es ws o O)
. 9 8 meee 7 0
PL Osimerinib + chemotherapy
FLAURA2: On-treatment 80 MDetected
plasma EGFR mutation 2 60
clearance was prognostic 3 4 essai, gx el come, essa. Metected
but not predictive of benefit | & 20 120280) 210370) 70200) 80170) a ee ed
with osimertinib + ol
chemotherapy vs Osimertinib+ ” Osimertinib = Osimertinib+ | Osimertinib
i 4 Chemotherapy (n=140) Chemotherapy (n= 137),
osimertinib alone’ ery CS
Week 3 Week 6
PeerView
4. Janne PA et al, AACR 2024, Abstract CTOI7.
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Clinical Benefit With Osimertinib + Chemo vs Osimertinib Alone’
Patients With Baseline Detected
Plasma EGFR Mutation
iients With Baseline Nondetected
Plasma EGFR Mutation
"Oumar + cheneterary 333 SENG)
Suman women Los orne agen
Osmertnib +
Los Osimertinio + chemotherapy
» chemotherapy oe
Los Osimertn’s Lo2 osmertni
o LR 2060 (05% 01. 04500) y [HR 085 (95% 01.081172
8 6 Rn m à 3 De
Time From Randomization, mo Time From Randomization, mo
fio sek No. at oe
ESS es ws o O)
. 9 8 meee 7 0
PL Osimerinib + chemotherapy
FLAURA2: On-treatment 80 MDetected
plasma EGFR mutation 2 60
clearance was prognostic 3 4 essai, gx el come, essa. Metected
but not predictive of benefit | & 20 120280) 210370) 70200) 80170) a ee ed
with osimertinib + ol
chemotherapy vs Osimertinib+ ” Osimertinib = Osimertinib+ | Osimertinib
i 4 Chemotherapy (n=140) Chemotherapy (n= 137),
osimertinib alone’ ery CS
Week 3 Week 6
PeerView
4. Janne PA et al, AACR 2024, Abstract CTOI7.
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
+ Chemo vs ESMO 2025
Osimertinib Alone Regardless of Baseline Prognostic Factors Updates
OS by Baseline Prognostic Factors
Baseline CNS Metastases EGFR Mutation*
Osimertin +
= chemotherapy, mom year 08 (95% CH %
i
i
5
Plasma EGFRm ctDNA
ENTITY] CET)
on
(080-109)
on
oa
ql Tissue TP53
Sur os (6% CD 2 ET)
All Patients on!
Tyrer 08 po cn. En
HR SX EN
om
ne)
Data cur une 12,2025.
aan win Bin Erde and LOSR ae inuded in Extäde subgroup. A
Y dione PA tal. ESMO 2025 Abate LEAT? PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Osimertinib Alone Regardless of Baseline Prognostic Factors Updates
OS by Baseline Prognostic Factors
Baseline CNS Metastases EGFR Mutation*
Osimertin +
= chemotherapy, mom year 08 (95% CH %
i
i
5
Plasma EGFRm ctDNA
ENTITY] CET)
on
(080-109)
on
oa
ql Tissue TP53
Sur os (6% CD 2 ET)
All Patients on!
Tyrer 08 po cn. En
HR SX EN
om
ne)
Data cur une 12,2025.
aan win Bin Erde and LOSR ae inuded in Extäde subgroup. A
Y dione PA tal. ESMO 2025 Abate LEAT? PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
FLAURA2: Safety Update!
Osimertinid merino
AE + Chemotherapy i
(n=275) a
AE any cause, (0%) Dirnea
Any grade 276100) 20008) Nausea
Decreased appette
Grade 23 19370) 9434) ‘Gonatidtion
serous 12540) 78@27) ash
Outcome of death 22(8) 10 (4) Fatigue
‘Considered possibly related to Vomiting
s 201
treatment a a COVID-19
Leading to isconimuaton ofosimerin 34(12) 200) Sonal
Leading to discontinuation of pemetrexed 137.60) NA Paronychia
Leading to discontinuation of platinum 46 (17) NA ne u
Neutrophil count decreased
ALT increased
Dry skin
+ No new safety signals observed
+ AEs leading to discontinuation of osimertini remained low
+ No new treatment-related deaths observed with
osimertinib + chemo (vs 1 with osimertinib alone)
4. Planchard Det al WLC 2025, Abstract PLO2 04.
PeerView.com/EVZ827
Most Common AEs
<
a Osimertinis
m Grace 12
Grace 3
2 O0 2 40 60
Patients With AE, %
PeerView
Copyright © 2000-2025, PeerView
Osimertinid merino
AE + Chemotherapy i
(n=275) a
AE any cause, (0%) Dirnea
Any grade 276100) 20008) Nausea
Decreased appette
Grade 23 19370) 9434) ‘Gonatidtion
serous 12540) 78@27) ash
Outcome of death 22(8) 10 (4) Fatigue
‘Considered possibly related to Vomiting
s 201
treatment a a COVID-19
Leading to isconimuaton ofosimerin 34(12) 200) Sonal
Leading to discontinuation of pemetrexed 137.60) NA Paronychia
Leading to discontinuation of platinum 46 (17) NA ne u
Neutrophil count decreased
ALT increased
Dry skin
+ No new safety signals observed
+ AEs leading to discontinuation of osimertini remained low
+ No new treatment-related deaths observed with
osimertinib + chemo (vs 1 with osimertinib alone)
4. Planchard Det al WLC 2025, Abstract PLO2 04.
PeerView.com/EVZ827
Most Common AEs
<
a Osimertinis
m Grace 12
Grace 3
2 O0 2 40 60
Patients With AE, %
PeerView
Copyright © 2000-2025, PeerView
Phase 3 MARIPOSA: PFS Improved With 1L Amivant:
vs Osimertinib
Primary Endpoint: PFS by BICR?
Median PFS, mo (95% Cl)
Amivantamab
+ lazertinib 23.7 (19.1-27.7)
100 Osimertinib 16.6 (14.8-18.5)
80 HR = 0.70 (95% CI, 0.58-0.85); P < .001
E Median follow-up: 22 mo
go
Es Amivantamab + lazertinib
Osimertinib
2
of
0 3 6 8 12 15 18 21 24 21 30 35
Time, mo
No, a Risk
Aricanioms 425 391 357 202 201 244 104 106 00 233 0 0
Osmernb 420.404 358 325 256 208 180
"atthe time of prespecified final PF:
PeerView.com/EVZ827
90 45 2% 10 0
5 analysis there were a total of 444 PFS events i the amivantamab + lazerinib and osimerinis arms combined.
1.Cho BC etal ESMO 2023. Abstract LBAT4. 2. Cho BC et al. N Eng! Med. 2024.301:1488-1408. 3, Gadgeel Sel al. WCLO 2024. Abstract OA02.03.
MOS (interim analysis):
HR = 0.77
(95% Cl, 0.61-0.96;
P= .019); did not reach
prespecified level of
Statistical significance
Toxicities: paronychia,
IRR, rash, VTE
PeerView
Copyright © 2000-2025, PeerView
vs Osimertinib
Primary Endpoint: PFS by BICR?
Median PFS, mo (95% Cl)
Amivantamab
+ lazertinib 23.7 (19.1-27.7)
100 Osimertinib 16.6 (14.8-18.5)
80 HR = 0.70 (95% CI, 0.58-0.85); P < .001
E Median follow-up: 22 mo
go
Es Amivantamab + lazertinib
Osimertinib
2
of
0 3 6 8 12 15 18 21 24 21 30 35
Time, mo
No, a Risk
Aricanioms 425 391 357 202 201 244 104 106 00 233 0 0
Osmernb 420.404 358 325 256 208 180
"atthe time of prespecified final PF:
PeerView.com/EVZ827
90 45 2% 10 0
5 analysis there were a total of 444 PFS events i the amivantamab + lazerinib and osimerinis arms combined.
1.Cho BC etal ESMO 2023. Abstract LBAT4. 2. Cho BC et al. N Eng! Med. 2024.301:1488-1408. 3, Gadgeel Sel al. WCLO 2024. Abstract OA02.03.
MOS (interim analysis):
HR = 0.77
(95% Cl, 0.61-0.96;
P= .019); did not reach
prespecified level of
Statistical significance
Toxicities: paronychia,
IRR, rash, VTE
PeerView
Copyright © 2000-2025, PeerView
MARIPOSA: OS Was Significantly Longer With Amivantamab +
Lazertinib vs Osimertinibt:22-<
100 Median OS, mo (95% CI)
NR (42.9-NR)
| e 36.7 (33.4-41.0)
7 3
70 60 .75 (95% Cl, 0.61-0.92); P < 0.005
ze i
y Tf es nv tania
g 51 iazertinib
= 44
OS curves continue to Osimertinib
a projected >
»
Median follow-up: 37.8 mo
‘st se 6 « 8 & 9 © 8 & So o ow ww +
Anas + Time, mo
Mare 429 404 360 203 OS 33 HS mé NO 27 27 M2 6e wi 6 NW 1 ©
coment 2 46 400 8 dé Sk SO Mt ah 270 I dr tr OS O0 à
* Last pariipant ented in May 2022. Clinical cut date: December 4, 2024, In total 300 deaths ad occured inthe amivantamab + azerinb (173 deaths) and osimertin (217 deaths)
“arms. P calculated frm alogank test stratified by mutation type (Ex19del ar LASER), race (Asian or Non-Asian), and history of brain metastasis (present or absent, Hazard ratio calculated
‘tom a svalfied Cox regression model Based on an exponential distribution assumption of OS in both arms. PeerView
1. Yang JC-H etal ELOC 2025, Abstract 40.2 Yang JC-H et al N Engl J Med. Published online September 7, 2025.
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Lazertinib vs Osimertinibt:22-<
100 Median OS, mo (95% CI)
NR (42.9-NR)
| e 36.7 (33.4-41.0)
7 3
70 60 .75 (95% Cl, 0.61-0.92); P < 0.005
ze i
y Tf es nv tania
g 51 iazertinib
= 44
OS curves continue to Osimertinib
a projected >
»
Median follow-up: 37.8 mo
‘st se 6 « 8 & 9 © 8 & So o ow ww +
Anas + Time, mo
Mare 429 404 360 203 OS 33 HS mé NO 27 27 M2 6e wi 6 NW 1 ©
coment 2 46 400 8 dé Sk SO Mt ah 270 I dr tr OS O0 à
* Last pariipant ented in May 2022. Clinical cut date: December 4, 2024, In total 300 deaths ad occured inthe amivantamab + azerinb (173 deaths) and osimertin (217 deaths)
“arms. P calculated frm alogank test stratified by mutation type (Ex19del ar LASER), race (Asian or Non-Asian), and history of brain metastasis (present or absent, Hazard ratio calculated
‘tom a svalfied Cox regression model Based on an exponential distribution assumption of OS in both arms. PeerView
1. Yang JC-H etal ELOC 2025, Abstract 40.2 Yang JC-H et al N Engl J Med. Published online September 7, 2025.
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
MARIPOSA: Amivantamab + Lazertinib Showed a Clinically Meaningful
Improvement in Intracranial PFS With Durable Responses
Median Intracranial PFS,
mo (95% Cl)
‘Amivantamab
2” + kzerinb 25.4 (20.1-29.5)
el Osimertinib 22.2 (18.4-26.9)
a HR = 0.79 (95% Cl, 0.61-1.02); P = 0.07"
5 Se .
E
Eo 3-year landmark icPFS 36
E was 36% vs 18% for Amivantamab + lazertinib
É amivantamab + lazertinib
vs osimertinib
SI 6 8 m & © À À À + à à à à à à
Time, mo
Te 165 HE No 1 M2 M ® & 7% & 4 sn 1
II
oats
"Intracranial PES was defined as time from randomization ut the date of intracranial disease progression (progression of brain metastasis or occurence of new brain lesions) or death,
metastasss PP was calculated from a log-ank teat stated by mutation type (EX10del or LASER) and race
(Asian oF Non-Asian) Hazard ratio was calculated ftom a state Cox regression model
1. Yang UCM et aL ELCC 2025, Abstract 0.2 Yang JC-Hetal Engl. Med. Pushed onine September 7, 2025. PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Improvement in Intracranial PFS With Durable Responses
Median Intracranial PFS,
mo (95% Cl)
‘Amivantamab
2” + kzerinb 25.4 (20.1-29.5)
el Osimertinib 22.2 (18.4-26.9)
a HR = 0.79 (95% Cl, 0.61-1.02); P = 0.07"
5 Se .
E
Eo 3-year landmark icPFS 36
E was 36% vs 18% for Amivantamab + lazertinib
É amivantamab + lazertinib
vs osimertinib
SI 6 8 m & © À À À + à à à à à à
Time, mo
Te 165 HE No 1 M2 M ® & 7% & 4 sn 1
II
oats
"Intracranial PES was defined as time from randomization ut the date of intracranial disease progression (progression of brain metastasis or occurence of new brain lesions) or death,
metastasss PP was calculated from a log-ank teat stated by mutation type (EX10del or LASER) and race
(Asian oF Non-Asian) Hazard ratio was calculated ftom a state Cox regression model
1. Yang UCM et aL ELCC 2025, Abstract 0.2 Yang JC-Hetal Engl. Med. Pushed onine September 7, 2025. PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Multiple Studies Show TP53 Co-Alterations Are a Signal of
Poorer Prognosis in EGFRm NSCLC
Can Comutations Be Used MARIPOSA: PFS by TP53 Status?
as Prognostic Biomarkers?" TP53 Co-mutations
pa ms =
io u Pom
& HR (5% ch de asso
° » 2
Es Tem ED
8 2 Amivantamab + lazertinib
o
COS
PFS,
resamuvtsamit "86 TPS TS Gmat
om MPomarsem 108 TPsimutsom
TPE 126
pe Osimertnto 198 (142-238)
HR (85% C1) 0.75 082.107)
2 ss
Median few up: 22.0 mo
mon x a7
oo Woman mw © 5 1 0 0 oe Amivantamab + lazertinib
A > M os 8 a r
= simentinib
+ Comutations in TP53 and tumor suppressor genes
are associated with worse TKI outcomes noua TAO o
1. Sockhanme Petal There Oncol 2024.19:2£0251,2.Feip E ela, ASCO 2024. Ase luwiwsg mens ens PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Poorer Prognosis in EGFRm NSCLC
Can Comutations Be Used MARIPOSA: PFS by TP53 Status?
as Prognostic Biomarkers?" TP53 Co-mutations
pa ms =
io u Pom
& HR (5% ch de asso
° » 2
Es Tem ED
8 2 Amivantamab + lazertinib
o
COS
PFS,
resamuvtsamit "86 TPS TS Gmat
om MPomarsem 108 TPsimutsom
TPE 126
pe Osimertnto 198 (142-238)
HR (85% C1) 0.75 082.107)
2 ss
Median few up: 22.0 mo
mon x a7
oo Woman mw © 5 1 0 0 oe Amivantamab + lazertinib
A > M os 8 a r
= simentinib
+ Comutations in TP53 and tumor suppressor genes
are associated with worse TKI outcomes noua TAO o
1. Sockhanme Petal There Oncol 2024.19:2£0251,2.Feip E ela, ASCO 2024. Ase luwiwsg mens ens PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Improved PFS vs Osimerti
An EIERN
Se Melzense
A PRIT TT
MARIPOSA: = Seen tongs zane
PFS by Detectable £ so a
Baseline a
EGFRmut ctDNA'
TI Oe em a
SS a Ces we HE 6
Without Cleared EGFRm CtDNA? at Week 9
10 VEIT
MARIPOSA: Sam
PFS WithoutWith ¿e a
Cleared EGFRmut g ©
CtDNA at Week 9! À
9 3 5 +
Time, mo
Detecion of Extéel and LESER by Bicdesi daPCR.
1. Feip et al, ASCO 2024. Abstract 8504
ih
PeerView.com/EVZ827
MARIPOSA: Amivantamab + Lazertinib Yields Significantly
ib in High-Risk Disease
Amivantamab
12 18 10 21 24 27 30
PFS, %
i
‘Avienared + rain 27.7 @2.1-NE)
MR» 072 (05% 01,471.10) P= 192
asno 220
35%
Amivantamao
Turenne
21 8 21
Time, mo
‘With Cleared EGFRm ctDNA* at Week 9
2% à 30
i ‘Amwantamab
H ie
H osinerin’
HA=054 osx cv’,
Mecan
HET:
12 15 18 21 24 27 20
Time, mo
PeerView
Copyright © 2000-2025, PeerView
An EIERN
Se Melzense
A PRIT TT
MARIPOSA: = Seen tongs zane
PFS by Detectable £ so a
Baseline a
EGFRmut ctDNA'
TI Oe em a
SS a Ces we HE 6
Without Cleared EGFRm CtDNA? at Week 9
10 VEIT
MARIPOSA: Sam
PFS WithoutWith ¿e a
Cleared EGFRmut g ©
CtDNA at Week 9! À
9 3 5 +
Time, mo
Detecion of Extéel and LESER by Bicdesi daPCR.
1. Feip et al, ASCO 2024. Abstract 8504
ih
PeerView.com/EVZ827
MARIPOSA: Amivantamab + Lazertinib Yields Significantly
ib in High-Risk Disease
Amivantamab
12 18 10 21 24 27 30
PFS, %
i
‘Avienared + rain 27.7 @2.1-NE)
MR» 072 (05% 01,471.10) P= 192
asno 220
35%
Amivantamao
Turenne
21 8 21
Time, mo
‘With Cleared EGFRm ctDNA* at Week 9
2% à 30
i ‘Amwantamab
H ie
H osinerin’
HA=054 osx cv’,
Mecan
HET:
12 15 18 21 24 27 20
Time, mo
PeerView
Copyright © 2000-2025, PeerView
MARIPOSA: PFS Benefit With/Without CNS Metastases With
1L Amivantamab + Lazertinib in EGFRm mNSCLC13
With a History of Brain Metastases
Median PFS, mo
Without a History of Brain Metastases
Median PFS, mo
(95% Cl) (95% Cl)
‘Amivantamab +lazertinio 18.3 (16.6-23.7) Amivantamab + lazertinib 27.5 (22.1-NE)
Osimertinib 13.0 (12.2-16.4) Osimertinib 19.9 (16.6-22.9)
HR (95% Cl) 0.69 (0.53-0.92) HR (95% Cl) 0.69 (0.53-0.89)
100 00
” “0
=
* in Amivantamab + lazertinib Fe Amper leen
Lo Lo
a E
» Osimertinib 2 Osimertinib
AE ee err rr BEREETZITITEZT
Time, mo Time, mo
No. at Rak Mo, at isk
Anvartamab + aan +
AMD 178102 140194115 92 71 24 24 12 2 0 AMADA 291229211 198170152123 72 36 21 0
Osmernb — 172164146126 95 64 47 21 11 6 1 0
Osimerinb 257 240.212 190171141119 09 27 22 9 0
gi
4. Gho BO etal. ESMO 2023, AbstactLOAL4, 2. Cho BC et al. N Engl J Med, 2024201:1406-1498.9. FeipE el ASCO 2024. Abstract 8504. PeerView
PeerView.com/EVZ827
Copyright © 2000-2025, PeerView
1L Amivantamab + Lazertinib in EGFRm mNSCLC13
With a History of Brain Metastases
Median PFS, mo
Without a History of Brain Metastases
Median PFS, mo
(95% Cl) (95% Cl)
‘Amivantamab +lazertinio 18.3 (16.6-23.7) Amivantamab + lazertinib 27.5 (22.1-NE)
Osimertinib 13.0 (12.2-16.4) Osimertinib 19.9 (16.6-22.9)
HR (95% Cl) 0.69 (0.53-0.92) HR (95% Cl) 0.69 (0.53-0.89)
100 00
” “0
=
* in Amivantamab + lazertinib Fe Amper leen
Lo Lo
a E
» Osimertinib 2 Osimertinib
AE ee err rr BEREETZITITEZT
Time, mo Time, mo
No. at Rak Mo, at isk
Anvartamab + aan +
AMD 178102 140194115 92 71 24 24 12 2 0 AMADA 291229211 198170152123 72 36 21 0
Osmernb — 172164146126 95 64 47 21 11 6 1 0
Osimerinb 257 240.212 190171141119 09 27 22 9 0
gi
4. Gho BO etal. ESMO 2023, AbstactLOAL4, 2. Cho BC et al. N Engl J Med, 2024201:1406-1498.9. FeipE el ASCO 2024. Abstract 8504. PeerView
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Copyright © 2000-2025, PeerView
MARIPOSA: First Onset of Key AEs for 1L Amivantamab +
Lazertinib!
100
Median follow-up of 3e «o
37.8mo g
Es
H
E
Es
Mostfirstonset AEs | $
En
occur early (0-4 mo),
with longer-term follow- $
up showing no new 25 E 2 2 EL E 295 E
safety signals and 238358 5 25535 25 S
indicating that long- Ses au 25 3:65 2
term treatment gs 5 aan 5 o
is feasible g $ 2 2 2
a À a À 5
E à E à E
5 © ©
a fa) à
2 VTE a grouped tem, wich led pumonar embotam, ep vin thrombosis, ib venous thrombosis, venous fembot, rem, superf vin trombosis, temberhleits,
prior vena cava ayan, à m
1" Yang JC-Hetal ELOC 2025. Abstract 0. PeerView
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Lazertinib!
100
Median follow-up of 3e «o
37.8mo g
Es
H
E
Es
Mostfirstonset AEs | $
En
occur early (0-4 mo),
with longer-term follow- $
up showing no new 25 E 2 2 EL E 295 E
safety signals and 238358 5 25535 25 S
indicating that long- Ses au 25 3:65 2
term treatment gs 5 aan 5 o
is feasible g $ 2 2 2
a À a À 5
E à E à E
5 © ©
a fa) à
2 VTE a grouped tem, wich led pumonar embotam, ep vin thrombosis, ib venous thrombosis, venous fembot, rem, superf vin trombosis, temberhleits,
prior vena cava ayan, à m
1" Yang JC-Hetal ELOC 2025. Abstract 0. PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
MARIPOSA: Safety Update’
by Preferred Term’
Median duration of treatment Any grade
was 27.0 mo for amivantamab + Related to EGFR inhibition
Grade 23
fds Paronychia 294 (69) 49(12) 427 (20) 2)
lazertinib and 22.4 mo for Rash 271 (64) 73 (17) 136 (32) 3(<1)
osimertinib Diarrhea 133 (32) 92) 200 (47) 4)
A Dermatitis aeniform 127 60) zo 55 (13) o
A | pom wes 2 ah
ru 5) ) 1
Related to MET inhibition
~ AES were mostly EGFR: and | oe EI EI EI o
MET-related and grades 1-22 Ferrara 16268) 20 20) sn
er
A minority of participants were Infusion-related reaction 275 (65) 2716) © Gi
prescribed antibiotics for rash ALT increased 4170 (40) 2307) 86 (15) 20
(21%) at tty nation” aoe eT 1 u
ipaion
Few were on anticoagulation (5%) CovID-19 His HG een HE
3 a Anemia
o | ea E
lazertinib arm and 11% in the ere en E da ih yeh in
pa ma
osimertinib arm a 84 (20) 3) 26 (6) o
“Torombocyopenia 7408 au 204 sur
{VTE isa grouped te, which include pulmonary embolism, ceep ven tvombcsi, Imb venous Imembone, venous om, Porn, super vein thomberl,tombophiedis
emboiam venous embelsm Jaguar ven tvemboss, sgmod snus Irombons, aay ven Imamboss. purmerary met. Vend ca rombos, central venous eateterzaon, pot
an trombosis, pt trombote syndrome, pulmonary thrombosis, superior saga snus trombosa, wanaverse sn brombak, pele venous thrombosis,
and superior vena cava syndrome, * 220% of parücpants in ler grup. PeerView
‘T'ang JC el a ELCC 2025 Abate 40.2 Cho BC ela N Engl Med. 202£391:1480-148. 3. pia Aleta, NACLC 2022 Abstract PPO. O88.
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
by Preferred Term’
Median duration of treatment Any grade
was 27.0 mo for amivantamab + Related to EGFR inhibition
Grade 23
fds Paronychia 294 (69) 49(12) 427 (20) 2)
lazertinib and 22.4 mo for Rash 271 (64) 73 (17) 136 (32) 3(<1)
osimertinib Diarrhea 133 (32) 92) 200 (47) 4)
A Dermatitis aeniform 127 60) zo 55 (13) o
A | pom wes 2 ah
ru 5) ) 1
Related to MET inhibition
~ AES were mostly EGFR: and | oe EI EI EI o
MET-related and grades 1-22 Ferrara 16268) 20 20) sn
er
A minority of participants were Infusion-related reaction 275 (65) 2716) © Gi
prescribed antibiotics for rash ALT increased 4170 (40) 2307) 86 (15) 20
(21%) at tty nation” aoe eT 1 u
ipaion
Few were on anticoagulation (5%) CovID-19 His HG een HE
3 a Anemia
o | ea E
lazertinib arm and 11% in the ere en E da ih yeh in
pa ma
osimertinib arm a 84 (20) 3) 26 (6) o
“Torombocyopenia 7408 au 204 sur
{VTE isa grouped te, which include pulmonary embolism, ceep ven tvombcsi, Imb venous Imembone, venous om, Porn, super vein thomberl,tombophiedis
emboiam venous embelsm Jaguar ven tvemboss, sgmod snus Irombons, aay ven Imamboss. purmerary met. Vend ca rombos, central venous eateterzaon, pot
an trombosis, pt trombote syndrome, pulmonary thrombosis, superior saga snus trombosa, wanaverse sn brombak, pele venous thrombosis,
and superior vena cava syndrome, * 220% of parücpants in ler grup. PeerView
‘T'ang JC el a ELCC 2025 Abate 40.2 Cho BC ela N Engl Med. 202£391:1480-148. 3. pia Aleta, NACLC 2022 Abstract PPO. O88.
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Early Onset AEs Can Be ifi
Accessible Prophylactic Approaches‘
COCOON DM regimen
substantially reduced grade 22 STORE in one
substantially reduced IRRs?
Prophylactic anticoagulation
substantially reduced VTEs*
dermatologic AEs'
im 52 Hold reduction In = ~3-fold reduction in =
dermatologie AËe' x amivantamab IRRs ®
gin % ge ul so
gu z LEE > ~2-fold reduction
geo ET] En in VTEs
ED = =
£5 38.6% 67.6% 2 £ 20.0%
see 43% | 3° 3”
SE 3 225% 3 11.4%
LB] [34.3% En - En
= 5
E é
o o o
COCOON DM SoC DM Dexamethasone Standard IRR Any prophylactic No prophylactic
8-mg IRR management anticoagulation anticoagulation
Grades Grece D prophylaxis
Grade 2 Grade 2
FOR = 018 (85% ci, 0.00040), P<0.0001. PeerView
1. Yang JC-H et al ELOC 2025, Abstract 40:2. Grard N etal ELCC 2026, 3. Spra Al el al. Thorac Oncol 2025 20 800-818. 4. Scott SC etal. ASCO 2024.
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Accessible Prophylactic Approaches‘
COCOON DM regimen
substantially reduced grade 22 STORE in one
substantially reduced IRRs?
Prophylactic anticoagulation
substantially reduced VTEs*
dermatologic AEs'
im 52 Hold reduction In = ~3-fold reduction in =
dermatologie AËe' x amivantamab IRRs ®
gin % ge ul so
gu z LEE > ~2-fold reduction
geo ET] En in VTEs
ED = =
£5 38.6% 67.6% 2 £ 20.0%
see 43% | 3° 3”
SE 3 225% 3 11.4%
LB] [34.3% En - En
= 5
E é
o o o
COCOON DM SoC DM Dexamethasone Standard IRR Any prophylactic No prophylactic
8-mg IRR management anticoagulation anticoagulation
Grades Grece D prophylaxis
Grade 2 Grade 2
FOR = 018 (85% ci, 0.00040), P<0.0001. PeerView
1. Yang JC-H et al ELOC 2025, Abstract 40:2. Grard N etal ELCC 2026, 3. Spra Al el al. Thorac Oncol 2025 20 800-818. 4. Scott SC etal. ASCO 2024.
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
COCOON DM:
+ Oral doxycycline or
minocycline (100
mg twice daily;
weeks 1-12)
Clindamycin 1%
(on scalp daily;
weeks 13-52)
Chlorhexidine 4%
(on fingernails and
toenails daily)
Ceramide-based
moisturizer (on
body and face at
least daily)
1. Byong CC et al. WCLC 2025. Abstract P3.12:8,
PeerView.com/EVZ827
Participants, %
COCOON OM grade 2
P< 0001
so 75
COCOON OM: grace 3
P< 0001
(280 OM: grace 2
"SOC DM: grade 3
P= 7618
COCOONDM SOCDM COCOONDM SOCOM GOCOONDM SOCOM
a 9-75 an ne (o=21) me
Grade > DAEIs DAEIS Involving Skin ,
(Primary Endpoint) (Excluding Paronychia) ainia
100 P= pos P< poor P= 0004
y
COCOONDM 7 soc DM
Geek n= 28)
DAEIS Involving Scalp
COCOONDM 7 SOCDM _COCOONDM SOCOM
Geek (n= 48) (= 20) (n= 48)
DAEIS Involving Face DAEIS Involving Body
PeerView
Copyright © 2000-2025, PeerView
+ Oral doxycycline or
minocycline (100
mg twice daily;
weeks 1-12)
Clindamycin 1%
(on scalp daily;
weeks 13-52)
Chlorhexidine 4%
(on fingernails and
toenails daily)
Ceramide-based
moisturizer (on
body and face at
least daily)
1. Byong CC et al. WCLC 2025. Abstract P3.12:8,
PeerView.com/EVZ827
Participants, %
COCOON OM grade 2
P< 0001
so 75
COCOON OM: grace 3
P< 0001
(280 OM: grace 2
"SOC DM: grade 3
P= 7618
COCOONDM SOCDM COCOONDM SOCOM GOCOONDM SOCOM
a 9-75 an ne (o=21) me
Grade > DAEIs DAEIS Involving Skin ,
(Primary Endpoint) (Excluding Paronychia) ainia
100 P= pos P< poor P= 0004
y
COCOONDM 7 soc DM
Geek n= 28)
DAEIS Involving Scalp
COCOONDM 7 SOCDM _COCOONDM SOCOM
Geek (n= 48) (= 20) (n= 48)
DAEIS Involving Face DAEIS Involving Body
PeerView
Copyright © 2000-2025, PeerView
Rates of Amivantamab + Lazertinib Disc nuations Red
Dose Modifications of Amivantamab/Lazertinib Due to AEs
Dermatologic AEs Any AEs
=COCOON DM "SOC DM =COCOONDM "SOC DM
Participants, %
Participants, %
8 6 8 8
Dose Interruption Dose Reduction Discontinuation
Dose Interruption Dose Reduction
+ Participants using the COCOON DM regimen had lower rates of amivantamab or
lazertinib discontinuations due to AEs (11% vs 19% for SOC)
+ VTE was observed in 6% of participants with COCOON DM vs 7% with SOC DM
1. Yang JC-H etal ELOO 2025, Abstract 40.
PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Dose Modifications of Amivantamab/Lazertinib Due to AEs
Dermatologic AEs Any AEs
=COCOON DM "SOC DM =COCOONDM "SOC DM
Participants, %
Participants, %
8 6 8 8
Dose Interruption Dose Reduction Discontinuation
Dose Interruption Dose Reduction
+ Participants using the COCOON DM regimen had lower rates of amivantamab or
lazertinib discontinuations due to AEs (11% vs 19% for SOC)
+ VTE was observed in 6% of participants with COCOON DM vs 7% with SOC DM
1. Yang JC-H etal ELOO 2025, Abstract 40.
PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
PALOMA-3: Amivantamab SC + Lazertinib Shows Noninferiority to
IV Regimen and Improved OS in Refractory EGFRm NSCLC*2
ORR, % (95% CI)
All responders.
Confirmed
responders
Best response, n (%)
CR
PR
sD
PD
NE
DCR, % (95% Cl)
‘Median TTR (range), mo
30 (24-37)
Relative risk, 0.92 (0.70-1.23); P= 001
27 (21-33)
ntamab IV
(n=212)
33 (26-39)
27 (21-33)
Relative risk, 0.99 (0.72-1.36); P< .001
105)
61 (30)
93 (45)
37 (18)
147)
75 (69-81)
15(1269)
105)
68 (32)
81 (38)
42 (20)
20 (9)
71 (64-77)
15 (1.2.9.9)
1. Leight N et al ASCO 2024. LBASSOS, 2. Leigh! NB e al. J Gin Oncol, 2024,42:3603 3805.
PeerView.com/EVZ827
®
Lg
2% ame
¿jo (9%. 428.1) sc enwantemad
¿jo en
ibe
é
E
=
SC amivatama
ge en
22”
ER N amartama
zer as
ato
HR or death = 0.62 (5% I. 042-082)
ol
oa. 6 » ae
tama Time Since Date of Random Assignment, mo
PeerView
Copyright © 2000-2025, PeerView
IV Regimen and Improved OS in Refractory EGFRm NSCLC*2
ORR, % (95% CI)
All responders.
Confirmed
responders
Best response, n (%)
CR
PR
sD
PD
NE
DCR, % (95% Cl)
‘Median TTR (range), mo
30 (24-37)
Relative risk, 0.92 (0.70-1.23); P= 001
27 (21-33)
ntamab IV
(n=212)
33 (26-39)
27 (21-33)
Relative risk, 0.99 (0.72-1.36); P< .001
105)
61 (30)
93 (45)
37 (18)
147)
75 (69-81)
15(1269)
105)
68 (32)
81 (38)
42 (20)
20 (9)
71 (64-77)
15 (1.2.9.9)
1. Leight N et al ASCO 2024. LBASSOS, 2. Leigh! NB e al. J Gin Oncol, 2024,42:3603 3805.
PeerView.com/EVZ827
®
Lg
2% ame
¿jo (9%. 428.1) sc enwantemad
¿jo en
ibe
é
E
=
SC amivatama
ge en
22”
ER N amartama
zer as
ato
HR or death = 0.62 (5% I. 042-082)
ol
oa. 6 » ae
tama Time Since Date of Random Assignment, mo
PeerView
Copyright © 2000-2025, PeerView
PALOMA-3: Amivantamab SC + Lazertinib Shows Safety Profile
Consistent With IV With Lower Rate of IRRs and VTE"
The safety profile of amivantamab SC was con:
with fewer IRRs (13% vs 66%) and VTE (9% vs 14%)
Incidence of IRR-Related Symptoms Rates of VTE by Treatment Arm
and Prophylaxis Status
ts, all grades 13 ca
Infuslon-etated AES G2) ba a 5 SC Ami IV Ami
nd [an Grade> m .
Orgone 3 2 ge] Grade2 m =
sea E
‘Vomiting 2 15 3 E Grade 1 =
Cough 2 2
Hypoxia 2 es
Hypotension 1 ¿5
Sinus tachycardia 2 ES
Erythema 1 SE
Chest discomfort 08 58
‘Hypertension 08 es
Fuma 12
DRE = 206 = 210 n= 164 ne 171
100 75 50 25 0 25 50 75 100 All Patients On Prophylactic
% Anticoagulation
1. Leigh N et al ASCO 2024. LBABEOS. 2. Leigh NB e al. J Gin Oncol, 2024,42:3603 3805.
PeerView.com/EVZ827
n=42 n=39
No Prophylactic
Anticoagulation
PeerView
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Consistent With IV With Lower Rate of IRRs and VTE"
The safety profile of amivantamab SC was con:
with fewer IRRs (13% vs 66%) and VTE (9% vs 14%)
Incidence of IRR-Related Symptoms Rates of VTE by Treatment Arm
and Prophylaxis Status
ts, all grades 13 ca
Infuslon-etated AES G2) ba a 5 SC Ami IV Ami
nd [an Grade> m .
Orgone 3 2 ge] Grade2 m =
sea E
‘Vomiting 2 15 3 E Grade 1 =
Cough 2 2
Hypoxia 2 es
Hypotension 1 ¿5
Sinus tachycardia 2 ES
Erythema 1 SE
Chest discomfort 08 58
‘Hypertension 08 es
Fuma 12
DRE = 206 = 210 n= 164 ne 171
100 75 50 25 0 25 50 75 100 All Patients On Prophylactic
% Anticoagulation
1. Leigh N et al ASCO 2024. LBABEOS. 2. Leigh NB e al. J Gin Oncol, 2024,42:3603 3805.
PeerView.com/EVZ827
n=42 n=39
No Prophylactic
Anticoagulation
PeerView
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PALOMA-2 (Cohort 5): Consistent Response Rate With 1L SC
Q4W Amivantamab + Lazertinib!
Best Confirmed Overall Response by INV (n = 75)
geo fon
5 Dermatitis acneiform
de Stomatitis 29038) 364)
5% Pruritus 26134) 101
SE Diarrhea 22 (29) 23)
Bo Associated with MET inhibition
ba Hypoalbuminemia 4964) 4(5)
33 Peripheral edema 2836) 0
3 oe Other
Increased ALT 25(2) 34)
Increased AST 21 (27) 14)
Dry skin 1823) 0
+ Investigator-assessed ORR: 82% (95% Cl, 71-90)
+ Independent Central Review-assessed ORR: 87% (95% Cl, 77-94)
1. Seot SO el al. WCLO 2025. PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Q4W Amivantamab + Lazertinib!
Best Confirmed Overall Response by INV (n = 75)
geo fon
5 Dermatitis acneiform
de Stomatitis 29038) 364)
5% Pruritus 26134) 101
SE Diarrhea 22 (29) 23)
Bo Associated with MET inhibition
ba Hypoalbuminemia 4964) 4(5)
33 Peripheral edema 2836) 0
3 oe Other
Increased ALT 25(2) 34)
Increased AST 21 (27) 14)
Dry skin 1823) 0
+ Investigator-assessed ORR: 82% (95% Cl, 71-90)
+ Independent Central Review-assessed ORR: 87% (95% Cl, 77-94)
1. Seot SO el al. WCLO 2025. PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Selection of Emerging
CTONG 2008
(FLOWERS)
ACROSS2
TROPION-
Lung14
TROPION-
Lung15
PeerView.com/EVZ827
Phase
Phase 2
Phase 3
Phase 3
Phase 3
Eligibility
EGFRm NSCLC with de novo
MET amplification and/or
overexpression
EGFRm (Ex19del, L858R) +
tumor suppressor genes
mutations
EGFRm (exon 19 deletion or
L858R) NSCLC
EGFRm (exon 19 deletion or
L858R) NSCLC
e Combinations
Treatment Arm
Osimertinib +
savolitinib
Almonertinib +
Chemo
Osimertinib + dato-
Dxd
Osimertinib +/- dato-
Dxd
Almonertinib
Osimertinib
Platinum doublet
chemotherapy
PeerView
Copyright © 2000-2025, PeerView
CTONG 2008
(FLOWERS)
ACROSS2
TROPION-
Lung14
TROPION-
Lung15
PeerView.com/EVZ827
Phase
Phase 2
Phase 3
Phase 3
Phase 3
Eligibility
EGFRm NSCLC with de novo
MET amplification and/or
overexpression
EGFRm (Ex19del, L858R) +
tumor suppressor genes
mutations
EGFRm (exon 19 deletion or
L858R) NSCLC
EGFRm (exon 19 deletion or
L858R) NSCLC
e Combinations
Treatment Arm
Osimertinib +
savolitinib
Almonertinib +
Chemo
Osimertinib + dato-
Dxd
Osimertinib +/- dato-
Dxd
Almonertinib
Osimertinib
Platinum doublet
chemotherapy
PeerView
Copyright © 2000-2025, PeerView
Let’s Discuss A Case
A 60-year-old woman with no history of smoking presents
with cough, dyspnea, and generalized fatigue persistent
for 3 months
Let’s Discuss
PET/CT reveals 3-cm LLL lung nodule and enlarged
mediastinal nodes + multiple FDG-avid hepatic
hypodensities and extensive bone marrow uptake c/w
skeletal metastasis
MRI of the brain: 4 subcentimeter parenchymal lesions c/w
metastases and without perilesional edema
FNA of the lung lesion shows adenocarcinoma (TTF-1+)
Biomarker testing reveals EGFR exon 21 L858R mutation;
PD-L1 TPS <1%
PeerView.com/EVZ827
What 1L treatment would
you recommend for this patient
and why?
How do you decide between
monotherapy vs combination
therapy?
How would you coordinate with your
team and with external experts
about AE prophylaxis/management?
When would you consider SQ
formulations?
Copyright © 2000-2
A 60-year-old woman with no history of smoking presents
with cough, dyspnea, and generalized fatigue persistent
for 3 months
Let’s Discuss
PET/CT reveals 3-cm LLL lung nodule and enlarged
mediastinal nodes + multiple FDG-avid hepatic
hypodensities and extensive bone marrow uptake c/w
skeletal metastasis
MRI of the brain: 4 subcentimeter parenchymal lesions c/w
metastases and without perilesional edema
FNA of the lung lesion shows adenocarcinoma (TTF-1+)
Biomarker testing reveals EGFR exon 21 L858R mutation;
PD-L1 TPS <1%
PeerView.com/EVZ827
What 1L treatment would
you recommend for this patient
and why?
How do you decide between
monotherapy vs combination
therapy?
How would you coordinate with your
team and with external experts
about AE prophylaxis/management?
When would you consider SQ
formulations?
Copyright © 2000-2
Case Variations
What if the patient...
Presents with liver metastasis?
Presents with a co-occurring TP53 mutation?
Has detectable ctDNA at baseline but cleared/didn't clear?
Is much older (86) or much younger (40)?
Lives in a remote area 6 hours away from your clinic?
Had a solitary brain metastasis on MRI of the brain? Multiple brain metastases?
PeerView.com/EVZ827 Copyright © 2000-2025, Pee
What if the patient...
Presents with liver metastasis?
Presents with a co-occurring TP53 mutation?
Has detectable ctDNA at baseline but cleared/didn't clear?
Is much older (86) or much younger (40)?
Lives in a remote area 6 hours away from your clinic?
Had a solitary brain metastasis on MRI of the brain? Multiple brain metastases?
PeerView.com/EVZ827 Copyright © 2000-2025, Pee
Navigating the Changing Arsenal of Therapies for
Pretreated EGFR-Mutated Advanced/Metastatic
NSCLC
Pretreated EGFR-Mutated Advanced/Metastatic
NSCLC
Targeted Therapy’
Clonal Evolution Through EGFR-Targeted Therapy
1. Passar À et al ESMO Open. 2020:5:6000010. 2. Roper N etal. Cll Rep Med. 2020:1:100007.
PeerView.com/EVZ827
sformation After EGFR:
Osimertinib Resistance Mechanism:
Acquired Mutations and SCLC Transformation
First-Line Second-Line (T790M+)
None boven an; EGFR MKRNT-BRAF
CTNNS4 KRAS & mal ol
sue = Jor
rts
None MET amp
em. on
fra
ST À
‘me
None Bt) os
con
(PD-L1) amp
PeerView
Copyright © 2000-2025, PeerView
Clonal Evolution Through EGFR-Targeted Therapy
1. Passar À et al ESMO Open. 2020:5:6000010. 2. Roper N etal. Cll Rep Med. 2020:1:100007.
PeerView.com/EVZ827
sformation After EGFR:
Osimertinib Resistance Mechanism:
Acquired Mutations and SCLC Transformation
First-Line Second-Line (T790M+)
None boven an; EGFR MKRNT-BRAF
CTNNS4 KRAS & mal ol
sue = Jor
rts
None MET amp
em. on
fra
ST À
‘me
None Bt) os
con
(PD-L1) amp
PeerView
Copyright © 2000-2025, PeerView
FLAURA2: No Novel Resistance Mechanisms Were Detected
Osimertinib
‘ (n= 99)
mtn mo
ston
COQ ‘iscontin E
” = | — Satin € coer tai A ———— Le m
wm
om core trom |
wo EGFR C7O7S i wo nam
om corr oneruonmen | so. 40
wm 0m METamptfcaton | "nan
2 ww Eras wm
wm Rar Veco CT
wm KRAS mon 0 te
wm IICA tion me
om CONDES ampicaton | so sm
0 OK amptteaten “so
w m RET fusion 1 w so)
wm RAF fusion om
wm AK fon ms
CT Omer oncogeni fusion — om
m Rat lee 1 vu nm
men m P53 alteration CT A NE |
Joncremonerary J ec exioce
cames | EOFRLESER
+ Acquired resistance mechanisms remained generally similar between osimertinib + chemo and osimertinib monotheray
1. Yang 6 ot al. WLC 2024. Abstract MAIZ. PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Osimertinib
‘ (n= 99)
mtn mo
ston
COQ ‘iscontin E
” = | — Satin € coer tai A ———— Le m
wm
om core trom |
wo EGFR C7O7S i wo nam
om corr oneruonmen | so. 40
wm 0m METamptfcaton | "nan
2 ww Eras wm
wm Rar Veco CT
wm KRAS mon 0 te
wm IICA tion me
om CONDES ampicaton | so sm
0 OK amptteaten “so
w m RET fusion 1 w so)
wm RAF fusion om
wm AK fon ms
CT Omer oncogeni fusion — om
m Rat lee 1 vu nm
men m P53 alteration CT A NE |
Joncremonerary J ec exioce
cames | EOFRLESER
+ Acquired resistance mechanisms remained generally similar between osimertinib + chemo and osimertinib monotheray
1. Yang 6 ot al. WLC 2024. Abstract MAIZ. PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
MARIPOSA: Distinct Mechanisms of Resistance to 1L Osimertinib
and Amivantamab + Lazertinib!
Osimert Amivaniamab + Lazertn
EOT Acauired Resistance EOT Acauired Resistance
ESFRMET dependent EGPRMET independent EOERMET EGPRNET dependent
E a econ
it Eg her
sine resort
| um EE
1
ren i a on
ce 7 um cc
sn Gor tf uit |
wimp ER win me maten mu ons men = Fen
+ Acquired resistance mutational landscape is different in 1L osimertinib and amivantamab + lazertinib
+ Acquired MET amplifications and EGFR resistance mutations were less frequent with amivantamab + lazertinib than osimertinib
1. Hayashi et at WCLE 2025. Absra PT1.3.08, PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
and Amivantamab + Lazertinib!
Osimert Amivaniamab + Lazertn
EOT Acauired Resistance EOT Acauired Resistance
ESFRMET dependent EGPRMET independent EOERMET EGPRNET dependent
E a econ
it Eg her
sine resort
| um EE
1
ren i a on
ce 7 um cc
sn Gor tf uit |
wimp ER win me maten mu ons men = Fen
+ Acquired resistance mutational landscape is different in 1L osimertinib and amivantamab + lazertinib
+ Acquired MET amplifications and EGFR resistance mutations were less frequent with amivantamab + lazertinib than osimertinib
1. Hayashi et at WCLE 2025. Absra PT1.3.08, PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
MARIPOSA-2: Amivantamab + Chemo Is 2L SOC in E
NSCLC After Osimertinib12
+ Ata median follow-up of 8.7 mo, amivantamab + chemotherapy and amivantamab + lazertinib +
chemotherapy reduced the risk of progression of death by 52% and 56%, respectively
PFS by BICR
Amivantamab + chemotherapy Amiventamab + lazertinib +
vs copy chemotherapy" vs chemotherapy
PFS. 8.30842 m0
FAO GER CI OF DES) FRS DA GRC OE0)
Peut Peur
MPES:63v942m0
* 60
¢ p
Ë a
2 . Consistent PFS benefit by
er investigator
o MS :
a 7 7 a er HR = 0.41 (8.2 vs 4.2 mo;
No at Risk Time, mo P< 001%)
Amivantamab + chemo 131 so “9 2 7 o + HR, 0.38 (8.3 vs 4.2 mo;
‘Amivantamab +iazerinib + chemo 263 194 104 52 a 4 o P<.001)
Creme is om Ze 5 o
“panne seo henterapy amines al pate rare ofthe des ene reste.
"Nominal P value; endpoint not
of hierarchical hypothesis testing
Y Pass et ol EMO 2009. Aline BATS 2 Passar Atal Ann Oncol 202636770.
PeerView
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NSCLC After Osimertinib12
+ Ata median follow-up of 8.7 mo, amivantamab + chemotherapy and amivantamab + lazertinib +
chemotherapy reduced the risk of progression of death by 52% and 56%, respectively
PFS by BICR
Amivantamab + chemotherapy Amiventamab + lazertinib +
vs copy chemotherapy" vs chemotherapy
PFS. 8.30842 m0
FAO GER CI OF DES) FRS DA GRC OE0)
Peut Peur
MPES:63v942m0
* 60
¢ p
Ë a
2 . Consistent PFS benefit by
er investigator
o MS :
a 7 7 a er HR = 0.41 (8.2 vs 4.2 mo;
No at Risk Time, mo P< 001%)
Amivantamab + chemo 131 so “9 2 7 o + HR, 0.38 (8.3 vs 4.2 mo;
‘Amivantamab +iazerinib + chemo 263 194 104 52 a 4 o P<.001)
Creme is om Ze 5 o
“panne seo henterapy amines al pate rare ofthe des ene reste.
"Nominal P value; endpoint not
of hierarchical hypothesis testing
Y Pass et ol EMO 2009. Aline BATS 2 Passar Atal Ann Oncol 202636770.
PeerView
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MARIPOSA-2 Update: Amivantamab + Chemo Shows Improving
OS Trend vs Chemo Alone’
Amivantamab-chemotherapy continues to demonstrate a clear and improving
OS trend vs chemotherapy®
¿o
5 MARIPOSA-2is ongoing and
2 @ ‘will proceed to final OS
3 analysis as planned
5
B® 60
2 Median follow-up: 18.1 mo Amivantamab +
24 Cl, mo chemotherapy
Amivantamab
5 RC
5 2 Chemotherapy
2
&
o
0 3 6 9 12, 15 18 21 24 2
Time,
No. at Risk
‘Amivantarnab
a A 124 ns 101 8 ss 39 15 a o
Chemotherapy 269 242 213 174 147 103 49 2 6 o
18-mo landmark for OS was 50% for amivantamab + chemotherapy vs 40% for chemotherapy
"OS beneft of amivantamab-chemotherapy vs chemotherapy was general consistent among pre-defined subgroups. P value Is from a logrank test stated by
csimerinIne of therapy (sine vs secandine, story e bain metastases (js or o), and Asian ace (yes va ro) OS was evakated ata 2 add alpha 100142 DoorView
4 Popat Set al ESMO 2024. Abstract LBAS4,
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
OS Trend vs Chemo Alone’
Amivantamab-chemotherapy continues to demonstrate a clear and improving
OS trend vs chemotherapy®
¿o
5 MARIPOSA-2is ongoing and
2 @ ‘will proceed to final OS
3 analysis as planned
5
B® 60
2 Median follow-up: 18.1 mo Amivantamab +
24 Cl, mo chemotherapy
Amivantamab
5 RC
5 2 Chemotherapy
2
&
o
0 3 6 9 12, 15 18 21 24 2
Time,
No. at Risk
‘Amivantarnab
a A 124 ns 101 8 ss 39 15 a o
Chemotherapy 269 242 213 174 147 103 49 2 6 o
18-mo landmark for OS was 50% for amivantamab + chemotherapy vs 40% for chemotherapy
"OS beneft of amivantamab-chemotherapy vs chemotherapy was general consistent among pre-defined subgroups. P value Is from a logrank test stated by
csimerinIne of therapy (sine vs secandine, story e bain metastases (js or o), and Asian ace (yes va ro) OS was evakated ata 2 add alpha 100142 DoorView
4 Popat Set al ESMO 2024. Abstract LBAS4,
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PALOMA-2 (Cohort 3b): Consistent ORR and PFS Benefit Wit! ESMO 2025
Updates
PFS by INV
‘est Change From Baseline in
‘S00 of Target Lesions, %
fi
Amivantama + chemo
+ y è
mo ic uo No. at Rik 22 e > . o
In the post-osimertinib setting, the efficacy of amivantamab SC Q3W + chemo is consistent with that
of amivantamab IV Q3W + chemo, with the added tolerability and convenience benefits of an SC
formulation, further supporting its use as a new SOC for patients with EGFR-mutated advanced
NSCLC after disease progression on osimertinib
1. Nadal Eo a. ESMO 2026, Abtract 1960. PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Updates
PFS by INV
‘est Change From Baseline in
‘S00 of Target Lesions, %
fi
Amivantama + chemo
+ y è
mo ic uo No. at Rik 22 e > . o
In the post-osimertinib setting, the efficacy of amivantamab SC Q3W + chemo is consistent with that
of amivantamab IV Q3W + chemo, with the added tolerability and convenience benefits of an SC
formulation, further supporting its use as a new SOC for patients with EGFR-mutated advanced
NSCLC after disease progression on osimertinib
1. Nadal Eo a. ESMO 2026, Abtract 1960. PeerView
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COMPEL: Assessing Benefits of Osimertinib + Chemo in EGFRm
Advanced NSCLC Following Non-CNS Progression on 1L Osimertinib*
Primary Analysis: PFS
3
Events/Patients, n (%) Median PFS, mo (95% Ci
Osimertinib + chemotherapy 32/49 (65) 8.4 (5.7-11.8)
08 Osimerinib 42149 (86) 44 (2556)
HR (95% Cl) 0.43 (0.27-0.70)
Maturity: 76%
Median follow-up, mo (range):
Osimertinib + chemotherapy, 5.4 (<0.1-24.9)
Placebo + chemotherapy, 5.5 (<0.1-11.1)
Probability of PFS
25
Osimertinib + chemotherapy
Osimertinib
00
o 12 18 30
Time From Randomization, mo
No. at Risk
Osimertni + chemotherapy 49 » A 2 1 o
Osimertnio s sa 3 o o o
Osimertinib + chemotherapy was associated with improved PFS vs placebo + chemotherapy
PFS: HR = 0.43 (95% Cl, 0.27-0.70), mPFS: 8.4 vs 4.4mo (N= 98)
OS: HR = 0.71 (95% CI, 0.42-1.23); MOS: 15.9 vs 9.8 mo (N = 98)
Longer CNS PFS in patients without baseline CNS metastases (n = 75)
Improvement in non-CNS PFS (N = 98), suggesting that benefit extends beyond the CNS
+. Paseo G tal. VICLO 202, Alu OAD. PeerView
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Advanced NSCLC Following Non-CNS Progression on 1L Osimertinib*
Primary Analysis: PFS
3
Events/Patients, n (%) Median PFS, mo (95% Ci
Osimertinib + chemotherapy 32/49 (65) 8.4 (5.7-11.8)
08 Osimerinib 42149 (86) 44 (2556)
HR (95% Cl) 0.43 (0.27-0.70)
Maturity: 76%
Median follow-up, mo (range):
Osimertinib + chemotherapy, 5.4 (<0.1-24.9)
Placebo + chemotherapy, 5.5 (<0.1-11.1)
Probability of PFS
25
Osimertinib + chemotherapy
Osimertinib
00
o 12 18 30
Time From Randomization, mo
No. at Risk
Osimertni + chemotherapy 49 » A 2 1 o
Osimertnio s sa 3 o o o
Osimertinib + chemotherapy was associated with improved PFS vs placebo + chemotherapy
PFS: HR = 0.43 (95% Cl, 0.27-0.70), mPFS: 8.4 vs 4.4mo (N= 98)
OS: HR = 0.71 (95% CI, 0.42-1.23); MOS: 15.9 vs 9.8 mo (N = 98)
Longer CNS PFS in patients without baseline CNS metastases (n = 75)
Improvement in non-CNS PFS (N = 98), suggesting that benefit extends beyond the CNS
+. Paseo G tal. VICLO 202, Alu OAD. PeerView
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TROPION-Lung01: PFS by Histology’
NsQ Squamous
With and Without AGA With and Without AGA
m = on: Dato-D»
O PORC SERA) DARA) o O (enc)
2 MR GE cp esposo 0 HR 66%) ET)
nr % a ns OR. °2 ar
ke 2 ES ss &
zu Zo
¢ E
ES E
” “o
» »
0 o
9 2. 6 8 © E Ww D 2. 6 8 D 2 1 à
Time Since Randomization, mo Time Since Randomization, mo
Der Nostra
oo m m @ à m7 1 0 asm 4 6 6 4 + 41
Ducenmi 2215 ee
PFS HR for NSQ without AGAs: 0.71 (0.56-0.91) )
1.Ahn Metal, ESMO 2023, Abstract LBA12.
PeerView
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Copyright © 2000-2025, PeerView
NsQ Squamous
With and Without AGA With and Without AGA
m = on: Dato-D»
O PORC SERA) DARA) o O (enc)
2 MR GE cp esposo 0 HR 66%) ET)
nr % a ns OR. °2 ar
ke 2 ES ss &
zu Zo
¢ E
ES E
” “o
» »
0 o
9 2. 6 8 © E Ww D 2. 6 8 D 2 1 à
Time Since Randomization, mo Time Since Randomization, mo
Der Nostra
oo m m @ à m7 1 0 asm 4 6 6 4 + 41
Ducenmi 2215 ee
PFS HR for NSQ without AGAs: 0.71 (0.56-0.91) )
1.Ahn Metal, ESMO 2023, Abstract LBA12.
PeerView
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Copyright © 2000-2025, PeerView
Dato-DXd Versus Docetaxel in Patients With NSCLC: Final OS by
Histology From TROPION-Lung01'
Nonsquamous Squamous
= Delo OKE Don = Sate RT Docs
100 — 100 ——o
TO (124-160) 12200710) TERT 766010 9402128)
80 REC 0.84 068-108 80 Rec 1320091192
2 60 x 60
o 7
© 40 © 40
Dato-Dxd
2 20 148 Docetaxel
5 o Jato-DXd
0 2 4 6 & 10 12 14 16 16 20 22 24 26 26 30 32 M 0 2 4 6 & 10 12 14 16 18 20 22 24 26 28 30 32 34
Time, mo Time, mo
No. at Rsk No. at Risk
Dato-Dxd "204220200 100161 141 130112 97 76 63 46 31 20 15 4 1 O DaloDXd 65 52 42 39 29 27 21 12 9 8 8 5 4 2 1100
Docetaxel 234206 106 161 190125111 92 79 06 50 32 22 12 0 3 2 0 Dooetaxel 71 67 52 44 36 32 27 20 19 15 138 4 3 3 1 0 0
= In patents with NSQ histology, 16% risk reduction for death and 2.3-mo improvement in median OS with Dato-DX4
+ OS improvements in the NSQ subset were seen regardless of actionable genomic alteration status:
~ Present: 15.6 mo vs 9.6 mo (HR [95% Ci] = 0.65 0 40-1 08) absent: 13.6 mo vs 12.3 mo (HR [95% Cl] = 0.69 [0.70-1.13)
‘ala cta March 1, 2024 * Based onthe number of pers inthe respective actionable genomic ataton subsets.
Vos ware cau ateo on Dan da in escort case repo fms, A
"Sandee ete stot, Al ADS 0 = PeerView
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Histology From TROPION-Lung01'
Nonsquamous Squamous
= Delo OKE Don = Sate RT Docs
100 — 100 ——o
TO (124-160) 12200710) TERT 766010 9402128)
80 REC 0.84 068-108 80 Rec 1320091192
2 60 x 60
o 7
© 40 © 40
Dato-Dxd
2 20 148 Docetaxel
5 o Jato-DXd
0 2 4 6 & 10 12 14 16 16 20 22 24 26 26 30 32 M 0 2 4 6 & 10 12 14 16 18 20 22 24 26 28 30 32 34
Time, mo Time, mo
No. at Rsk No. at Risk
Dato-Dxd "204220200 100161 141 130112 97 76 63 46 31 20 15 4 1 O DaloDXd 65 52 42 39 29 27 21 12 9 8 8 5 4 2 1100
Docetaxel 234206 106 161 190125111 92 79 06 50 32 22 12 0 3 2 0 Dooetaxel 71 67 52 44 36 32 27 20 19 15 138 4 3 3 1 0 0
= In patents with NSQ histology, 16% risk reduction for death and 2.3-mo improvement in median OS with Dato-DX4
+ OS improvements in the NSQ subset were seen regardless of actionable genomic alteration status:
~ Present: 15.6 mo vs 9.6 mo (HR [95% Ci] = 0.65 0 40-1 08) absent: 13.6 mo vs 12.3 mo (HR [95% Cl] = 0.69 [0.70-1.13)
‘ala cta March 1, 2024 * Based onthe number of pers inthe respective actionable genomic ataton subsets.
Vos ware cau ateo on Dan da in escort case repo fms, A
"Sandee ete stot, Al ADS 0 = PeerView
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TROPION-Lung05: Phase 2 Study of Dato-DXd in Previously
Treated NSCLC With Actionable Genomic Alterations’?
Efficacy Summary 7
All Patients Patients >
Responses Treated With EGFR With ALK m1
per BICR Patients Mutations Rearrangement 2
wem mer n= 38) E
ORR confirmed. 4008) 34(430) 8(235) al UE ñ mt, A
NO) TEA (824553) (107412) Een fa myth at nn Us
Median DOR, 7 7 7 nu u pul]
ma (4.2.9.8) (4.2-10.2) (28-84) “Es N
(25% ch L tramos m 18.0088)
DCR confirmed, 108 (78.8) 64 (82.1) 25 (73.5)
nn (%) (95% CI) (71.0-85.3) (717-898) (55.6-87.1)
Median PFS, mo 54 58 43
(95% Cl) (5.4-8.3) (2.6-6.9)
BOR: In the overall population (n = 137), four patients (3%) achieved a
CR and 45 (33%) achieved a PR
+ EGFR subset: Among patients with sensitizing or T790M mutations mame ae
(n = 68), the ORR was 49.1% in those previously treated with osimertinib women © ARAS
5
À Pa eta £940 2003 Ata I 2 Sade tal Om ASS 1250126 PeerView
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Treated NSCLC With Actionable Genomic Alterations’?
Efficacy Summary 7
All Patients Patients >
Responses Treated With EGFR With ALK m1
per BICR Patients Mutations Rearrangement 2
wem mer n= 38) E
ORR confirmed. 4008) 34(430) 8(235) al UE ñ mt, A
NO) TEA (824553) (107412) Een fa myth at nn Us
Median DOR, 7 7 7 nu u pul]
ma (4.2.9.8) (4.2-10.2) (28-84) “Es N
(25% ch L tramos m 18.0088)
DCR confirmed, 108 (78.8) 64 (82.1) 25 (73.5)
nn (%) (95% CI) (71.0-85.3) (717-898) (55.6-87.1)
Median PFS, mo 54 58 43
(95% Cl) (5.4-8.3) (2.6-6.9)
BOR: In the overall population (n = 137), four patients (3%) achieved a
CR and 45 (33%) achieved a PR
+ EGFR subset: Among patients with sensitizing or T790M mutations mame ae
(n = 68), the ORR was 49.1% in those previously treated with osimertinib women © ARAS
5
À Pa eta £940 2003 Ata I 2 Sade tal Om ASS 1250126 PeerView
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| Biomarker: TROP2 Normalized Membrane Ratio
Measured by Quantitative Continuous Scoring!
+ QCS is a novel, fully-supervised computational pathology approach that precisely quantifies and locates
targets such as TROP2
IHC with D Whole suse ‘Automated image Patient biomarker
TROP2 assay 9 imaging analysis (QCS) status determination
a 275% of tumor cells
4 ie D\ with TROP2 NMR 50.56
NE 400 <75% of tumor cells
= with TROP2 NMR 50.56"
Differentiates tumor Measures OD in each tumor cell Calculates TROP2 NMR
from nontumor for every tumor cell
‘Membrane OD
Membrane OD + cytoplasm OD
3 Membrane and cytoplasm Lower NMR —+ higher cytoplasm
= ‘optical density (OD) proportion
2 01>25% of ces wäh an NUR 2056. PeerView
1. Garassino MC et al WCLC 2024, Abstract PLO2.11,
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Measured by Quantitative Continuous Scoring!
+ QCS is a novel, fully-supervised computational pathology approach that precisely quantifies and locates
targets such as TROP2
IHC with D Whole suse ‘Automated image Patient biomarker
TROP2 assay 9 imaging analysis (QCS) status determination
a 275% of tumor cells
4 ie D\ with TROP2 NMR 50.56
NE 400 <75% of tumor cells
= with TROP2 NMR 50.56"
Differentiates tumor Measures OD in each tumor cell Calculates TROP2 NMR
from nontumor for every tumor cell
‘Membrane OD
Membrane OD + cytoplasm OD
3 Membrane and cytoplasm Lower NMR —+ higher cytoplasm
= ‘optical density (OD) proportion
2 01>25% of ces wäh an NUR 2056. PeerView
1. Garassino MC et al WCLC 2024, Abstract PLO2.11,
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
TROPION-Lung01: NMR of TROP2 by QCS Is Predictive of
Clinical Outcomes’
Overall BEP: Efficacy by TROP2 QCS-NMR Status + TROP2 NMR as measured by QCS reflected the
TROP2 QCS-NMR positivity is predictive for longer PFS with Dato-DXd expression of TROP2 in the membrane relative to total
in the biomarker-evaluable population (n = 352) TROP2 (membrane and cytoplasm) and predicted
‘outcomes in an exploratory TROPION-Lung01
on analysis.
- TROP2 QCS-NMR+ was more prevalent in patients
ORR, % 327 103 169 154 with nonsquamous vs squamous histology
75 Modan PES, mo 69 41 29 4 (66% vs 44%)
x PES HR OSHC) 057041070) 1.16 078170) - Patients receiving Dato-DXd who were TROP2
so Treatment by biomarker status interaction: P = QCS-NMR+ had a higher ORR and longer PFS
ES compared with those who were TROP2 QCS-NMR-
ee - Overall grade 23 AE rates with Dato-DXd were
25 Dato-DXd, fauna similar regardless of TROP2 QCS-NMR status
SER 1. QCS.NMR- + Further investigation of this promising biomarker is
0 ‘ongoing in the first-line advanced/metastatic NSCLC
0 4 3 12 16 trials AVANZAR (NCTO5687266) and TROPION-Lung
Time From Randomization, mo 10 (NCTO6357533)
TROP2 QCS-NMR has the potential to be the first TROP2 biomarker and the first computational pathology
biomarker for predicting clinical response to Dato-DXd in NSCLC.
‘ata cate March 29 2023
PFS HR (86% Cl) by TROP2 QCS-NMR status (+ vs -) within treatment. Dato-DXd: 0.48 (0.33-0.69); docetaxel: 0.97 (0.68-1.39) Ji
Frans MG ett WOLC 2024. Alatrcl PLOZ 1 PeerView
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Clinical Outcomes’
Overall BEP: Efficacy by TROP2 QCS-NMR Status + TROP2 NMR as measured by QCS reflected the
TROP2 QCS-NMR positivity is predictive for longer PFS with Dato-DXd expression of TROP2 in the membrane relative to total
in the biomarker-evaluable population (n = 352) TROP2 (membrane and cytoplasm) and predicted
‘outcomes in an exploratory TROPION-Lung01
on analysis.
- TROP2 QCS-NMR+ was more prevalent in patients
ORR, % 327 103 169 154 with nonsquamous vs squamous histology
75 Modan PES, mo 69 41 29 4 (66% vs 44%)
x PES HR OSHC) 057041070) 1.16 078170) - Patients receiving Dato-DXd who were TROP2
so Treatment by biomarker status interaction: P = QCS-NMR+ had a higher ORR and longer PFS
ES compared with those who were TROP2 QCS-NMR-
ee - Overall grade 23 AE rates with Dato-DXd were
25 Dato-DXd, fauna similar regardless of TROP2 QCS-NMR status
SER 1. QCS.NMR- + Further investigation of this promising biomarker is
0 ‘ongoing in the first-line advanced/metastatic NSCLC
0 4 3 12 16 trials AVANZAR (NCTO5687266) and TROPION-Lung
Time From Randomization, mo 10 (NCTO6357533)
TROP2 QCS-NMR has the potential to be the first TROP2 biomarker and the first computational pathology
biomarker for predicting clinical response to Dato-DXd in NSCLC.
‘ata cate March 29 2023
PFS HR (86% Cl) by TROP2 QCS-NMR status (+ vs -) within treatment. Dato-DXd: 0.48 (0.33-0.69); docetaxel: 0.97 (0.68-1.39) Ji
Frans MG ett WOLC 2024. Alatrcl PLOZ 1 PeerView
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Combined TROPION-Lung05 and -0112
EGFR Mutation Profile (n = 117)
Events/Patients, n
Exon 20 Ins; Exon 20
Actionable 20S: 797s: 0.9%
Genomic HR for PFS
Alterations Docetaxel
‘Absent 187/249 1827254 0.85
Present 26/50 36/51 mo 0.35
513%
Absent 162249 185/254 097
1
Present 33/50 33/51 eH 0.66
° O1
m ol Exon 21
Favors Favors L858R: 31.6%
Dato-DXd Docetaxel
1. An MY la ESMO Asia 2024, Abstract LBA. 2. Ao MU et a. J Thora Oncol 2025, PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
EGFR Mutation Profile (n = 117)
Events/Patients, n
Exon 20 Ins; Exon 20
Actionable 20S: 797s: 0.9%
Genomic HR for PFS
Alterations Docetaxel
‘Absent 187/249 1827254 0.85
Present 26/50 36/51 mo 0.35
513%
Absent 162249 185/254 097
1
Present 33/50 33/51 eH 0.66
° O1
m ol Exon 21
Favors Favors L858R: 31.6%
Dato-DXd Docetaxel
1. An MY la ESMO Asia 2024, Abstract LBA. 2. Ao MU et a. J Thora Oncol 2025, PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Combined TROPION-Lung05 and -0112
PFS and OS in the EGFRm Pool (|
117)
100 Median PFS, mo (95% Cl)
Response # 80 5.8 (5.4-8.2)
Confirmed ORR, n (%) 50 (42.7) 43 (44.8) 5 60 48.5
(95% CI) (836-522) (46-553) D 4
BOR, n (%) mes E EGFRm pool
CR 543) 402 o 1 H
PR 45 (38.5) 39 (40.6) 012345678 9 10111213 14 15 16 17 18 19
SD 48 (41) 37 (38.5) No. at Risk. Time, mo
a ROH 320 2021) EOFRm pool 117 115401 86 77 61 42 24 31 20 17 17 13 11 10 10 4 2 2 0
PD 12103) 10(10.4) Median OS, mo (95% Cl)
NE 464 1142) 100 834 15.6 (13.1-19.0)
20 647
Median DOR, mo (95% Cl) 7(4.29.8) 6.9 (4.2-9.8) 8 60
DCR, n (%) 101 (86.3) 82(85.4) 8 4
(95% CI) (787-920) (76.7-91.8)
Median PFS, mo (95% CI) 5.8(54-82) 5.7(5.4-7.9) 20 EGFRm pool
Median OS, mo (95% Cl) 15.6 (13.1-19.0) 14.7 (130-183) 9 + ne
01234567 8 9 10111213 141516 17 18192021
No. at Risk Time, mo
EGFR pool 117117113109103 88 84 68 95 80 77 73 68 63 53 47 35 M 19 12 6 0
1. An MU la ESMO Asia 2024, Absracl LBA. 2. Ao MJ ea. J Thora Oncol 2025, PeerView
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
PFS and OS in the EGFRm Pool (|
117)
100 Median PFS, mo (95% Cl)
Response # 80 5.8 (5.4-8.2)
Confirmed ORR, n (%) 50 (42.7) 43 (44.8) 5 60 48.5
(95% CI) (836-522) (46-553) D 4
BOR, n (%) mes E EGFRm pool
CR 543) 402 o 1 H
PR 45 (38.5) 39 (40.6) 012345678 9 10111213 14 15 16 17 18 19
SD 48 (41) 37 (38.5) No. at Risk. Time, mo
a ROH 320 2021) EOFRm pool 117 115401 86 77 61 42 24 31 20 17 17 13 11 10 10 4 2 2 0
PD 12103) 10(10.4) Median OS, mo (95% Cl)
NE 464 1142) 100 834 15.6 (13.1-19.0)
20 647
Median DOR, mo (95% Cl) 7(4.29.8) 6.9 (4.2-9.8) 8 60
DCR, n (%) 101 (86.3) 82(85.4) 8 4
(95% CI) (787-920) (76.7-91.8)
Median PFS, mo (95% CI) 5.8(54-82) 5.7(5.4-7.9) 20 EGFRm pool
Median OS, mo (95% Cl) 15.6 (13.1-19.0) 14.7 (130-183) 9 + ne
01234567 8 9 10111213 141516 17 18192021
No. at Risk Time, mo
EGFR pool 117117113109103 88 84 68 95 80 77 73 68 63 53 47 35 M 19 12 6 0
1. An MU la ESMO Asia 2024, Absracl LBA. 2. Ao MJ ea. J Thora Oncol 2025, PeerView
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OptiTROP-Lung04: Sac-TMT Demonstrated Statistically ESMO 2025
Significant Improvements in PFS and OS vs Chemo! Updates
PFS by BICR* OS by BICR
m EA o wenn air
pests soo von qi OR GENCY arma 840955
1
e 1 1058
5 00 1 zo
2 1 HR: 0.49 95% C1, 036-062) 5 HR 080 05% 1.044082)
Eo 323 Poo 8 « ‘waned 001"
= SaeTNT =
o — o 4
9 3 6 + 2 15 % A À D 3 6 8 2 5 8 À A
Time, mo. Time, mo.
Ho. at Rsk Neat Rsk
Ste 14 we @ 6 er Serum We se 467 1887 17 ISSO
Chemo m 125 1 2 1 6 4 0 Ghee 18 ND A2 UT 132 NO #7 1 0
Sac-TMT significantly improved PFS with 51% At the interim analysis, sac-TMT significantly
lower risk of PD or death improved PFS with 40% lower risk of PD or death
ata cult: Juy 8: 2025.
"For prespecifed PFS IA (daa cutof July 11, 2024), HR = 0.47 (95% Cl, 025:.82).P.<.0001. "Bases on prespecified OS IA, 2-sded P value was les than the
prespecified efficacy Boundary to achieve sltcalysignifcant improvement (2-skded aipha level of 0124 determines by the o'Brien-Fleming alpha spending funcion),
1 Zhang Let al ESMO 2025, Abstract LBAS.
PeerView
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Significant Improvements in PFS and OS vs Chemo! Updates
PFS by BICR* OS by BICR
m EA o wenn air
pests soo von qi OR GENCY arma 840955
1
e 1 1058
5 00 1 zo
2 1 HR: 0.49 95% C1, 036-062) 5 HR 080 05% 1.044082)
Eo 323 Poo 8 « ‘waned 001"
= SaeTNT =
o — o 4
9 3 6 + 2 15 % A À D 3 6 8 2 5 8 À A
Time, mo. Time, mo.
Ho. at Rsk Neat Rsk
Ste 14 we @ 6 er Serum We se 467 1887 17 ISSO
Chemo m 125 1 2 1 6 4 0 Ghee 18 ND A2 UT 132 NO #7 1 0
Sac-TMT significantly improved PFS with 51% At the interim analysis, sac-TMT significantly
lower risk of PD or death improved PFS with 40% lower risk of PD or death
ata cult: Juy 8: 2025.
"For prespecifed PFS IA (daa cutof July 11, 2024), HR = 0.47 (95% Cl, 025:.82).P.<.0001. "Bases on prespecified OS IA, 2-sded P value was les than the
prespecified efficacy Boundary to achieve sltcalysignifcant improvement (2-skded aipha level of 0124 determines by the o'Brien-Fleming alpha spending funcion),
1 Zhang Let al ESMO 2025, Abstract LBAS.
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HARMONi: Ivonescimab + Chemo in Patients With EGFRm
NSCLC Progressed on EGFR TKI Therapy’
Events, Median, HR a
= min mo eske ? 00 SNe mo” peon
Tones 952 _
hey 12908) 88 (drag 00 Fe 60 188 pel, OD
0 Pracebo
Pete ayy MOUS) 48 # Pato py MOM
cy
E æ 6
¢ A
= 8
“0
40 Ionescimab +
Seen
20 | mean FU:223m6 edan ru
20 À overt 207m
Mans EU, 2.2 mo
o
os 6 9 @ 6 TREE BE o
0.3 6 8 2 1 1m oe a7 30 53 35 30
Time, mo Time, mo
roma sem
a z 20 20 6 ww ns ss
E mn m 4» » 6 0 0
1. Gokiman Jet al WCLO 2025. PLO2.12.
PeerView.com/EVZ827
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NSCLC Progressed on EGFR TKI Therapy’
Events, Median, HR a
= min mo eske ? 00 SNe mo” peon
Tones 952 _
hey 12908) 88 (drag 00 Fe 60 188 pel, OD
0 Pracebo
Pete ayy MOUS) 48 # Pato py MOM
cy
E æ 6
¢ A
= 8
“0
40 Ionescimab +
Seen
20 | mean FU:223m6 edan ru
20 À overt 207m
Mans EU, 2.2 mo
o
os 6 9 @ 6 TREE BE o
0.3 6 8 2 1 1m oe a7 30 53 35 30
Time, mo Time, mo
roma sem
a z 20 20 6 ww ns ss
E mn m 4» » 6 0 0
1. Gokiman Jet al WCLO 2025. PLO2.12.
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SAVANNAH: Osimertinib + Savolitinib Showed Higher Antitumor
Activity Compared With Savolitinib + Placebo‘?
Osimertinib + Savolitinib in Locally Advanced or Metastatic EGFRm NSCLC
(PD on 1L osimertinib and confirmed MET overexpression or amplification)
Investigator-Assessed
‘Confirmed ORR, % (95% CI) 16 (5-36)
n 4
Median DOR, mo (95% Cl) 11.8 (6.0.NC) 45(26N0) 849117) 42(26N0)
Median time to onset of response, wk (OR) 6 (57-62) 61686. 616070) 616463
Savolitinib + Osimertinib BICR-Assessed Savolitinib + Placebo BICR-Assessed
ossess
in Target Lesion Size, %
Best Change From Baseline
sess
Best Change From Baseline
in Target Lesion Size, %
Best objective response PRESO MPD NE
B
Phase 3 SAFFRON study is ongoing: savolitinib + osimertinib vs chemo in patients with NSCLC after osimertinib? )
PeerView
1. Levy Bet al, ASCO 2025, Abstract 8513.2. hipslenialbials govlstudy/NCTOS2813007rank=t
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Activity Compared With Savolitinib + Placebo‘?
Osimertinib + Savolitinib in Locally Advanced or Metastatic EGFRm NSCLC
(PD on 1L osimertinib and confirmed MET overexpression or amplification)
Investigator-Assessed
‘Confirmed ORR, % (95% CI) 16 (5-36)
n 4
Median DOR, mo (95% Cl) 11.8 (6.0.NC) 45(26N0) 849117) 42(26N0)
Median time to onset of response, wk (OR) 6 (57-62) 61686. 616070) 616463
Savolitinib + Osimertinib BICR-Assessed Savolitinib + Placebo BICR-Assessed
ossess
in Target Lesion Size, %
Best Change From Baseline
sess
Best Change From Baseline
in Target Lesion Size, %
Best objective response PRESO MPD NE
B
Phase 3 SAFFRON study is ongoing: savolitinib + osimertinib vs chemo in patients with NSCLC after osimertinib? )
PeerView
1. Levy Bet al, ASCO 2025, Abstract 8513.2. hipslenialbials govlstudy/NCTOS2813007rank=t
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SACHI: Osimertinib + Savolitinib Improved mPFS in
MET-Amplified NSCLC Post 1L EGFR TKI’
Unresectable or Metastatic EGFRm NSCLC
(PD on 1L EGFR-TKI and centrally confirmed MET amplification [FISH+])
Prior 1st/2nd G EGFR-TKI-Treated Population ITT Population
Osimectinis
s Chematherapy
Ser oo)
u Es cn en mw a
se mers EEK Cho esos 544240 EN TOTS 95% GI. mo 8206112) 45/3054)
ES Seaited HR (SCD 034 (021058) pe States HR OSHC) 024 (025049)
La » ce a <om
so 20
a 4 5 «
23 Caiman + seit gx Cainer + alto
2 2 2 »
10 mora ‘0
lesen cyematerapy 4 Semen
RE RES AR 8 Rt 10 18: EEE ES
E Time, mo BR Time. mo
for the primary endpoint were met in both the prior
reated and ITT population:
=
1. Lu Shun tal ASCO 2025. Abstract LBABSOS PeerView
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MET-Amplified NSCLC Post 1L EGFR TKI’
Unresectable or Metastatic EGFRm NSCLC
(PD on 1L EGFR-TKI and centrally confirmed MET amplification [FISH+])
Prior 1st/2nd G EGFR-TKI-Treated Population ITT Population
Osimectinis
s Chematherapy
Ser oo)
u Es cn en mw a
se mers EEK Cho esos 544240 EN TOTS 95% GI. mo 8206112) 45/3054)
ES Seaited HR (SCD 034 (021058) pe States HR OSHC) 024 (025049)
La » ce a <om
so 20
a 4 5 «
23 Caiman + seit gx Cainer + alto
2 2 2 »
10 mora ‘0
lesen cyematerapy 4 Semen
RE RES AR 8 Rt 10 18: EEE ES
E Time, mo BR Time. mo
for the primary endpoint were met in both the prior
reated and ITT population:
=
1. Lu Shun tal ASCO 2025. Abstract LBABSOS PeerView
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Selected Trials on the Horizon for Pretreated EGFRm NSCLC
Phase _Elligibility
SAFFRON Phase 3 EGFRm and MET—
overexpressed and/or
amplification advanced
NSCLC after osimertinib
ORCHARD Phase 2 Advanced NSCLC after
osimertinib
NCT05194982 Phase 1 Advanced NSCLC
PeerView.com/EVZ827
Treatment Arm Control Primary
Arm Endpo
Chemo PFS
Savolitinib +
Osimertinib
Platform Study NA ORR
BL-B01D1 (EGFR X NA Safety and
HER3) RP2D
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Phase _Elligibility
SAFFRON Phase 3 EGFRm and MET—
overexpressed and/or
amplification advanced
NSCLC after osimertinib
ORCHARD Phase 2 Advanced NSCLC after
osimertinib
NCT05194982 Phase 1 Advanced NSCLC
PeerView.com/EVZ827
Treatment Arm Control Primary
Arm Endpo
Chemo PFS
Savolitinib +
Osimertinib
Platform Study NA ORR
BL-B01D1 (EGFR X NA Safety and
HER3) RP2D
PeerView
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Let’s Discuss A Case
A 65-year-old patient with locally advanced,
unresectable EGFRm NSCLC (EGFR exon 19 deletion,
PD-L1 TPS <1%) who started 1L osimertinib
After 14 months, imaging tests show pulmonary, liver, and
bone metastases
The patient remains asymptomatic
ECOG PS of 1
Repeated biomarker testing shows no new targetable
alterations
PeerView.com/EVZ827
Let's Discuss
What tests/assessment need to be done
before treatment decision?
What treatment would you recommend for
this patient and why?
How do we reconcile treatment intensity
and safety profiles with patient
preferences in routine practice?
What practical recommendations can we
offer the community oncology team about
the integration and use of ADC-based
therapies?
Copyright © 2000-2025, Pee
A 65-year-old patient with locally advanced,
unresectable EGFRm NSCLC (EGFR exon 19 deletion,
PD-L1 TPS <1%) who started 1L osimertinib
After 14 months, imaging tests show pulmonary, liver, and
bone metastases
The patient remains asymptomatic
ECOG PS of 1
Repeated biomarker testing shows no new targetable
alterations
PeerView.com/EVZ827
Let's Discuss
What tests/assessment need to be done
before treatment decision?
What treatment would you recommend for
this patient and why?
How do we reconcile treatment intensity
and safety profiles with patient
preferences in routine practice?
What practical recommendations can we
offer the community oncology team about
the integration and use of ADC-based
therapies?
Copyright © 2000-2025, Pee
Case Variations
What if the patient...
Received the FLAURA2 regimen as 1L therapy?
— Consideration of length of Rx on pemetrexed
Received the MARIPOSA regimen as 1L therapy?
Presents with MET amplification?
Progresses on 2L therapy and is willing to consider 3L options?
PeerView.com/EVZ827 Copyright © 200
What if the patient...
Received the FLAURA2 regimen as 1L therapy?
— Consideration of length of Rx on pemetrexed
Received the MARIPOSA regimen as 1L therapy?
Presents with MET amplification?
Progresses on 2L therapy and is willing to consider 3L options?
PeerView.com/EVZ827 Copyright © 200
Extending the Benefits of EGFR-Targeted
Therapies to Patients With EGFR Exon 20
Insertion Mutations
Therapies to Patients With EGFR Exon 20
Insertion Mutations
PAPILLON: 1L Amivantamab + Chemo Improved PFS and ORR
in EGFR Ex20ins-Mutated NSCLC‘
Primary Endpoint: PFS by BICR B 4 intamab + Chemotherapy
“Amivantamab + chemotherapy reduced sk of progression or death by 60% 3.
ense Py
2 i.
¢ I.
® Penn = Chemotherapy
<henoterey a:
2
| co if:
5 à à 5 6 à à 3
Be ig ww a . + HE
Consistent PFS benefit by investigator: : Das
12.9 v 6.9 mo (HR = 0.38 [95% Cl, 0.29-0.51]; P< .0001%)
+ Amivantamab + chemo vs chemo alone showed consistent PFS benefit across all predefined subgroups; significantly
higher ORR, longer DOR, and deeper mean reduction in tumor size; and longer PFS2, supporting the 1L use of
amivantamab + chemo; favorable interim OS trend (HR = 0.675; P= .106)
+ The safety profile of amivantamab + chemo was consistent with individual agents, with low rates of treatment-related
discontinuations with amivantamab (7%)
«Nomina Pale endo ns par a area hypothe tes :
‘Grand etal €SMO2009 Aalen on en PeerView
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in EGFR Ex20ins-Mutated NSCLC‘
Primary Endpoint: PFS by BICR B 4 intamab + Chemotherapy
“Amivantamab + chemotherapy reduced sk of progression or death by 60% 3.
ense Py
2 i.
¢ I.
® Penn = Chemotherapy
<henoterey a:
2
| co if:
5 à à 5 6 à à 3
Be ig ww a . + HE
Consistent PFS benefit by investigator: : Das
12.9 v 6.9 mo (HR = 0.38 [95% Cl, 0.29-0.51]; P< .0001%)
+ Amivantamab + chemo vs chemo alone showed consistent PFS benefit across all predefined subgroups; significantly
higher ORR, longer DOR, and deeper mean reduction in tumor size; and longer PFS2, supporting the 1L use of
amivantamab + chemo; favorable interim OS trend (HR = 0.675; P= .106)
+ The safety profile of amivantamab + chemo was consistent with individual agents, with low rates of treatment-related
discontinuations with amivantamab (7%)
«Nomina Pale endo ns par a area hypothe tes :
‘Grand etal €SMO2009 Aalen on en PeerView
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CHRYSALI
EGFR Ex20in
EGFR Exon 20
Prior Platinum
(N= 81)
ORR (IRC) 40%
mDOR (INV) 11.1 mo
mPFS (IRC) 8.3 mo
Key Toxicities
IRR (66% any grade, 3% grade
23); most commonly on C1D1
Derm: rash (86% any grade,
4% grade 23), paronychia (45%)
MET related: hypoalbuminemia
(27%), edema (18%)
Dose reduction: 13%;
dose discontinuation: 4%
1. Park Kt al. J Clin Oncol. 2021:30:3901-3402.
PeerView.com/EVZ827
Amivant
of Target Lesions, %
Besebessosuessssss
Best Change From Baseline in SOD
és
b Improved PFS and ORR in Pretreated
Mutated NSCLC!
Exon20ins location
1 Halcal region (762-786)
12 Near loop region (767-772)
2 Far loop region (773-775)
1 Not detected by DNA
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EGFR Ex20in
EGFR Exon 20
Prior Platinum
(N= 81)
ORR (IRC) 40%
mDOR (INV) 11.1 mo
mPFS (IRC) 8.3 mo
Key Toxicities
IRR (66% any grade, 3% grade
23); most commonly on C1D1
Derm: rash (86% any grade,
4% grade 23), paronychia (45%)
MET related: hypoalbuminemia
(27%), edema (18%)
Dose reduction: 13%;
dose discontinuation: 4%
1. Park Kt al. J Clin Oncol. 2021:30:3901-3402.
PeerView.com/EVZ827
Amivant
of Target Lesions, %
Besebessosuessssss
Best Change From Baseline in SOD
és
b Improved PFS and ORR in Pretreated
Mutated NSCLC!
Exon20ins location
1 Halcal region (762-786)
12 Near loop region (767-772)
2 Far loop region (773-775)
1 Not detected by DNA
PeerView
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Best Confirmed Overall Response by
INV (n = 63)
3
a
x ER so
€ Eso
3 2:
E Ego IMPFS (95% Cl mo — Amiantamen + he
a El E
is ii 7) Schemotnerapy 122 (04NE) Median folowup: 104 mo
E o
E ° y 8. y = 75
3 Per Time, mo
3 40 un. a ” = ° o
s os
2 go
ä -60 4 Qe 0
E 2 El
5 Arivaniamab > chemotherapy
É so | * Pertatrosponso 33 «
3 80 | a OS (95% CH. mo
5 u Stable disease E Seen
é ie & 7 Boy NENNE) Madan otowup: 104 mo
du o. o 3 y 7 5 5 7
E Pe Time, mo
ES o o o.
PeerView
1. Lim SM et a, WLC 2025. Abstract MADS 03,
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
INV (n = 63)
3
a
x ER so
€ Eso
3 2:
E Ego IMPFS (95% Cl mo — Amiantamen + he
a El E
is ii 7) Schemotnerapy 122 (04NE) Median folowup: 104 mo
E o
E ° y 8. y = 75
3 Per Time, mo
3 40 un. a ” = ° o
s os
2 go
ä -60 4 Qe 0
E 2 El
5 Arivaniamab > chemotherapy
É so | * Pertatrosponso 33 «
3 80 | a OS (95% CH. mo
5 u Stable disease E Seen
é ie & 7 Boy NENNE) Madan otowup: 104 mo
du o. o 3 y 7 5 5 7
E Pe Time, mo
ES o o o.
PeerView
1. Lim SM et a, WLC 2025. Abstract MADS 03,
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WU-KONG1B: Tumor Response Was Observed With Sunvozertinib in
Platinum-Pretreated EGFR Ex20ins—Mutated NSCLC‘
Tumor Response Random 200 mg(n=85) Random 300 mg (n= 89) All 300 mg (N = 107)
Objective response rate, n (%) 39 (45.9) 42 (47.2) 49 (45.8)
97.5% Cl 33.6-58.5 35.1-59.5 34.8-57.0
P <.0001 <.0001 <.0001
Disease control rate, n (%) 76 (89.4) 82 (92.1) 95 (88.8)
97.5% Cl 79.6-95.6 83.3-97.2 80.1-94.6
Best overall response, n (%)
CR 5(59) 3(3.4) 3(2.8)
PR 34 (40) 39 (43.8) 46 (43)
sD 37 (43.5) 40 (44.9) 46 (43)
PD 6 (7.1) 5 (5.6) 8 (7.5)
NE 3 (85) 2(2.2) 48.7)
FDA grants accelerated approval to sunvozertinib for metastatic
NSCLC with EGFR exon 20 insertion mutations on July 2, 2025
1. Yang JCH et a. Gin Oncol 2025 00:11 PeerView
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Platinum-Pretreated EGFR Ex20ins—Mutated NSCLC‘
Tumor Response Random 200 mg(n=85) Random 300 mg (n= 89) All 300 mg (N = 107)
Objective response rate, n (%) 39 (45.9) 42 (47.2) 49 (45.8)
97.5% Cl 33.6-58.5 35.1-59.5 34.8-57.0
P <.0001 <.0001 <.0001
Disease control rate, n (%) 76 (89.4) 82 (92.1) 95 (88.8)
97.5% Cl 79.6-95.6 83.3-97.2 80.1-94.6
Best overall response, n (%)
CR 5(59) 3(3.4) 3(2.8)
PR 34 (40) 39 (43.8) 46 (43)
sD 37 (43.5) 40 (44.9) 46 (43)
PD 6 (7.1) 5 (5.6) 8 (7.5)
NE 3 (85) 2(2.2) 48.7)
FDA grants accelerated approval to sunvozertinib for metastatic
NSCLC with EGFR exon 20 insertion mutations on July 2, 2025
1. Yang JCH et a. Gin Oncol 2025 00:11 PeerView
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Selection of Other Emerging EGFR TKls for EGFR Ex20ins—
Mutated NSCLC in 1L/2L/Beyond
WU-KONG15
WU-KONG28
REZILIENT1
REZILIENT1
FURVENT
BECOME
PeerView.com/EVZ827
Phase
Phase 2
Phase 3
Phase 2
Phase 3
Phase 3
Phase 2
Eligibility
EGFR-mutated NSCLC
1L EGFR ex20ins-mutated
NSCLC.
EGFR ex20ins-mutated
NSCLC after platinum-
based chemotherapy with
or without amivantamab
1L EGFR ex20ins-mutated
NSCLC.
1L EGFR ex20ins-mutated
NSCLC
Pretreated EGFR ex20ins-
mutated NSCLC
Treatment Arm
Sunvozertinib
Sunvozertinib
Zipalertinib
Zipalertinib + Chemo
Furmonertinib
Control
Arm
NA
Chemo
NA
Chemo
Chemo
NA
Primary
Endp«
PFS
PFS
Safety, PK,
ORR, DOR
Toxicity, PFS
PFS
ORR
PeerView
Copyright © 2000-2025, PeerView
Mutated NSCLC in 1L/2L/Beyond
WU-KONG15
WU-KONG28
REZILIENT1
REZILIENT1
FURVENT
BECOME
PeerView.com/EVZ827
Phase
Phase 2
Phase 3
Phase 2
Phase 3
Phase 3
Phase 2
Eligibility
EGFR-mutated NSCLC
1L EGFR ex20ins-mutated
NSCLC.
EGFR ex20ins-mutated
NSCLC after platinum-
based chemotherapy with
or without amivantamab
1L EGFR ex20ins-mutated
NSCLC.
1L EGFR ex20ins-mutated
NSCLC
Pretreated EGFR ex20ins-
mutated NSCLC
Treatment Arm
Sunvozertinib
Sunvozertinib
Zipalertinib
Zipalertinib + Chemo
Furmonertinib
Control
Arm
NA
Chemo
NA
Chemo
Chemo
NA
Primary
Endp«
PFS
PFS
Safety, PK,
ORR, DOR
Toxicity, PFS
PFS
ORR
PeerView
Copyright © 2000-2025, PeerView
Let’s Discuss A Case
A 55-year-old man presents with dyspnea
Workup testing reveals pleural effusion
Pleural fluid cytology positive for adenocarcinoma of lung
PET scan: multiple bilateral pulmonary nodules
ECOG PS 1
Liquid biopsy reveals an EGFR exon 20 insertion
mutation; tissue NGS from the resection sample shows
the same findings
PeerView.com/EVZ827
Y
Y
Let's Discuss
What treatment would you recommend for
this patient and why?
What are the downstream implications of
frontline therapy choices on sequential
treatment planning?
Copyright © 2000-
A 55-year-old man presents with dyspnea
Workup testing reveals pleural effusion
Pleural fluid cytology positive for adenocarcinoma of lung
PET scan: multiple bilateral pulmonary nodules
ECOG PS 1
Liquid biopsy reveals an EGFR exon 20 insertion
mutation; tissue NGS from the resection sample shows
the same findings
PeerView.com/EVZ827
Y
Y
Let's Discuss
What treatment would you recommend for
this patient and why?
What are the downstream implications of
frontline therapy choices on sequential
treatment planning?
Copyright © 2000-
The Expanding Role of EGFR-Targeted Therapy in
Earlier Disease Settings
Earlier Disease Settings
LAURA: Improved PFS With Osimertinib After
Chemoradiotherapy in Stage Ill EGFRm NSCLC!
1. Ramatngam SS ell. ASCO 2024. Abstract LEA PeerView
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Chemoradiotherapy in Stage Ill EGFRm NSCLC!
1. Ramatngam SS ell. ASCO 2024. Abstract LEA PeerView
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LAURA: Improved Trend Towards OS Benefit With Osimertinib*
Events, n (%) Median (95% Cl), mo_HR (95% CI)_ Log-Rank P
‘Osimertinib (n = 143) — 40 (28) 58.8 (541-NC)
Placebo (n = 73) 26 (36) 54 (42.1-NC)
82%
0.67 (0.40-1.14) 140
10
09
08
07
08
05
04
03
02
o1
7% 31% maturity
Osimertinib
Placebo
Probability of OS
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 68 69 72 75
i Time From Randomization, mo
No. at Risk
Osimertinib 143 142 138 135 133 130 129128 125123112 99 89 73 62 49 40 29 18 11
Placebo 73 73 71 70 68 65 64 63 62 60 56 44 35 26 23 15 11 10 7 5
642110
322100
55/69 (80%) patients who discontinued study treatment in the placebo group
received subsequent treatment with a 3rd-gen EGFR-TKI
1 Ramalngam SS ell. ELCO 2025. Abstract LEM PeerView
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Events, n (%) Median (95% Cl), mo_HR (95% CI)_ Log-Rank P
‘Osimertinib (n = 143) — 40 (28) 58.8 (541-NC)
Placebo (n = 73) 26 (36) 54 (42.1-NC)
82%
0.67 (0.40-1.14) 140
10
09
08
07
08
05
04
03
02
o1
7% 31% maturity
Osimertinib
Placebo
Probability of OS
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 68 69 72 75
i Time From Randomization, mo
No. at Risk
Osimertinib 143 142 138 135 133 130 129128 125123112 99 89 73 62 49 40 29 18 11
Placebo 73 73 71 70 68 65 64 63 62 60 56 44 35 26 23 15 11 10 7 5
642110
322100
55/69 (80%) patients who discontinued study treatment in the placebo group
received subsequent treatment with a 3rd-gen EGFR-TKI
1 Ramalngam SS ell. ELCO 2025. Abstract LEM PeerView
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ADAURA Primary Endpoint: Improved DFS With Adjuvant
Osimertinib at Updated Analysis’?
Stage IB-IIIA
Median DFS, mo (95% CI)
Osimertinib (n = 339)
Placebo (n = 343)
HR (95% Cl)
10
09
os
658 (61.7-NC)
28.1 (22.1-35.0)
0.27 021.034)
Maturity: 45%
Osimertinib: 28%
Placebo: 62%
Stage IIIA
Median DFS, mo (95%
Osimertinib (n = 233)
Placebo (n = 237)
HR (95% CI)
E
65.8 (54.4-NC)
21.9(166-27.5)
0:23 (0.18-030)
Maturity: 51%
Osimertinib: 32%
Placebo: 70%
§ 07 Osimertinib
3 06
Bos
E
os
go
02
e. H H i
i | i 2 H
9 5 2 0 À 0 % à à à © & 1 SAA sammen
Ho at Rak ney io az Time, mo.
E mom nop s oka mw mw mm me SR 8
PeerView
1. Herbst Ret al. ASCO 2023. Abstract LBAS. 2. Tsuboi M et al. N Eng! J Med. 2023.380:137-147.
PeerView.com/EVZ827
Copyright © 2000-2025, PeerView
Osimertinib at Updated Analysis’?
Stage IB-IIIA
Median DFS, mo (95% CI)
Osimertinib (n = 339)
Placebo (n = 343)
HR (95% Cl)
10
09
os
658 (61.7-NC)
28.1 (22.1-35.0)
0.27 021.034)
Maturity: 45%
Osimertinib: 28%
Placebo: 62%
Stage IIIA
Median DFS, mo (95%
Osimertinib (n = 233)
Placebo (n = 237)
HR (95% CI)
E
65.8 (54.4-NC)
21.9(166-27.5)
0:23 (0.18-030)
Maturity: 51%
Osimertinib: 32%
Placebo: 70%
§ 07 Osimertinib
3 06
Bos
E
os
go
02
e. H H i
i | i 2 H
9 5 2 0 À 0 % à à à © & 1 SAA sammen
Ho at Rak ney io az Time, mo.
E mom nop s oka mw mw mm me SR 8
PeerView
1. Herbst Ret al. ASCO 2023. Abstract LBAS. 2. Tsuboi M et al. N Eng! J Med. 2023.380:137-147.
PeerView.com/EVZ827
Copyright © 2000-2025, PeerView
AURA Secondary Endpoint: Improved OS?
Stage IB-IIIA Disease
Adjuvant osimertinib demonstrated a statistically and
clinically significant improvement in OS vs placebo in
the overall population of stage IB-IIIA disease
Sy 08 Rate,
Kamen
Osimerino ET]
Placebo 33 me
(Overall OS HR (95.02% CI) 0491034070)
< 0001
Osimertinib
{
Maturity: 18%, osimertinib: 12%,
Median follow-up for OS (censored
patients): osimer
placebo = 61.5 mo
Placebo
ib = 61.5 mo;
Stage IIHIIA Disease
Adjuvant osimertinib demonstrated a statistically and
clinically significant improvement in OS vs placebo in
the primary population of stage II-IIIA disease
54.08 Rat,
nec
Osimertnio 2 5008)
Placebo CRETE]
Overall OS HR (05.03% C) 049(0.23-073)
8
0008
Osimertinis
08, Proportion
Maturity: 21%; osimertinib, 15%;
Median follow-up for OS (censored
patients): osimertinib = 61.7 mo;
placebo = 60.4 mo. H
Placebo
Time Since Randomization, mo
1.Herbst el a ASCO 2023. Abstract LBAS. 2. Tsuboi Met al. N Eng! J Med. 2023,380:157-147.
PeerView.com/EVZ827
ECC)
Time Since Randomization, mo
PeerView
Copyright © 2000-2025, PeerView
Stage IB-IIIA Disease
Adjuvant osimertinib demonstrated a statistically and
clinically significant improvement in OS vs placebo in
the overall population of stage IB-IIIA disease
Sy 08 Rate,
Kamen
Osimerino ET]
Placebo 33 me
(Overall OS HR (95.02% CI) 0491034070)
< 0001
Osimertinib
{
Maturity: 18%, osimertinib: 12%,
Median follow-up for OS (censored
patients): osimer
placebo = 61.5 mo
Placebo
ib = 61.5 mo;
Stage IIHIIA Disease
Adjuvant osimertinib demonstrated a statistically and
clinically significant improvement in OS vs placebo in
the primary population of stage II-IIIA disease
54.08 Rat,
nec
Osimertnio 2 5008)
Placebo CRETE]
Overall OS HR (05.03% C) 049(0.23-073)
8
0008
Osimertinis
08, Proportion
Maturity: 21%; osimertinib, 15%;
Median follow-up for OS (censored
patients): osimertinib = 61.7 mo;
placebo = 60.4 mo. H
Placebo
Time Since Randomization, mo
1.Herbst el a ASCO 2023. Abstract LBAS. 2. Tsuboi Met al. N Eng! J Med. 2023,380:157-147.
PeerView.com/EVZ827
ECC)
Time Since Randomization, mo
PeerView
Copyright © 2000-2025, PeerView
NeoADAURA: The MPR Rate Was Significantly Higher With Both
Osimertinib-Containing Regimens’
Neoadjuvant osimertinib, with or without 50 Difference: 24% (95% CI, 15-32)
chemo, demonstrated statistically significant OR: 19.8 e 002% a 46853)
improvement in MPR rates vs chemo alone rita
(26% or 25% vs 2%) in resectable EGFRm 40 Difference: 23% (95% Cl, 15-22)
stage II-I18 NSCLC ‘OR: 19.3 (69.9% Cl, 17-217 4)
Interim EFS trends favored the osimertinib- Ben
containing arms (osimertinib + chemo HR = E 26 5
0.50; 99.8% Cl, 0.17-1.41; osimertinib $5 (95% CL 180.40) (95% ci. 17.0-34.0)
monotherapy HR = 0.73; 95% Cl, 0.40- 1.35) | ©
Fewer patients with an MPR had an EFS & 2
event vs patients without an MPR. =
(2% vs 18%)
‘Over 50% of patients with baseline N2 10
disease were down-staged at surgery with 2
osimertinib-containing arms vs 21% with (95% Cl, 00.6.0)
ae ° Osimertinib Osi tinib A
Safety findings were consistent with the Imertinib + Imertini bo +
known profiles of the individual agents re est re
PeerView
1. Chat Jet al. ASCO 2025. Abstract 8001
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Osimertinib-Containing Regimens’
Neoadjuvant osimertinib, with or without 50 Difference: 24% (95% CI, 15-32)
chemo, demonstrated statistically significant OR: 19.8 e 002% a 46853)
improvement in MPR rates vs chemo alone rita
(26% or 25% vs 2%) in resectable EGFRm 40 Difference: 23% (95% Cl, 15-22)
stage II-I18 NSCLC ‘OR: 19.3 (69.9% Cl, 17-217 4)
Interim EFS trends favored the osimertinib- Ben
containing arms (osimertinib + chemo HR = E 26 5
0.50; 99.8% Cl, 0.17-1.41; osimertinib $5 (95% CL 180.40) (95% ci. 17.0-34.0)
monotherapy HR = 0.73; 95% Cl, 0.40- 1.35) | ©
Fewer patients with an MPR had an EFS & 2
event vs patients without an MPR. =
(2% vs 18%)
‘Over 50% of patients with baseline N2 10
disease were down-staged at surgery with 2
osimertinib-containing arms vs 21% with (95% Cl, 00.6.0)
ae ° Osimertinib Osi tinib A
Safety findings were consistent with the Imertinib + Imertini bo +
known profiles of the individual agents re est re
PeerView
1. Chat Jet al. ASCO 2025. Abstract 8001
PeerView.com/EVZ827 Copyright © 2000-2025, PeerView
Let’s Discuss A Case
65-year-old woman, never-smoker, presents
and had CT of the chest and abdomen
persistent cough Let's Discuss
CT chest shows a 3.4-cm x LUL mass
PET scan demonstrates 3.0- x 2.6-cm, solid-appearing LUL mass
(SUV 5.3); pleural is normal, 1 hilar LN, no distant disease
Brain MRI negative for metastases
EBUS confirmed hilar nodal involvement
Transbronchial biopsy LUL mass: invasive lung adenocarcinoma
NGS: EGFR exon 19 deletion, PD-L1: 70%
Staged as: T3NO, stage IIB
The patient receives neoadjuvant cisplatin and pemetrexed (well-
tolerated with moderate response), undergoes robotic lobectomy
4 weeks later comes to your clinic to discuss next-steps in care
PeerView.com/EVZ827
What are the key considerations for the
approach and timing of biomarker testing?
How can we ensure effective
multidisciplinary treatment planning for
resectable EGFR-mutant NSCLC?
What therapy would you recommend and
why?
What if the patient is interested in EGFR-
targeted therapy but not chemotherapy?
When to consider EGFR-targeted
treatment as a neoadjuvant strategy?
What if the patient approaches the end of
the adjuvant osimertinib regimen but is
interested in continuing therapy?
Copyright © 2000-2025, PeerView
65-year-old woman, never-smoker, presents
and had CT of the chest and abdomen
persistent cough Let's Discuss
CT chest shows a 3.4-cm x LUL mass
PET scan demonstrates 3.0- x 2.6-cm, solid-appearing LUL mass
(SUV 5.3); pleural is normal, 1 hilar LN, no distant disease
Brain MRI negative for metastases
EBUS confirmed hilar nodal involvement
Transbronchial biopsy LUL mass: invasive lung adenocarcinoma
NGS: EGFR exon 19 deletion, PD-L1: 70%
Staged as: T3NO, stage IIB
The patient receives neoadjuvant cisplatin and pemetrexed (well-
tolerated with moderate response), undergoes robotic lobectomy
4 weeks later comes to your clinic to discuss next-steps in care
PeerView.com/EVZ827
What are the key considerations for the
approach and timing of biomarker testing?
How can we ensure effective
multidisciplinary treatment planning for
resectable EGFR-mutant NSCLC?
What therapy would you recommend and
why?
What if the patient is interested in EGFR-
targeted therapy but not chemotherapy?
When to consider EGFR-targeted
treatment as a neoadjuvant strategy?
What if the patient approaches the end of
the adjuvant osimertinib regimen but is
interested in continuing therapy?
Copyright © 2000-2025, PeerView
Faculty Perspectives & Key Takeaways
Copyright © 2000-2025,
Copyright © 2000-2025,
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