Navigating Rapid Changes in First- and Later-Line Treatment of EGFR-Mutated NSCLC: A Practical Framework for Optimal Biomarker Testing, Treatment Selection and Sequencing, and Adverse Event Management

Chair and Presenters Natasha B. Leighl, MD, MMSc, FRCPC, FASCO, Luis Paz-Ares, MD, PhD, and Joshua Sabari, MD, discuss NSCLC in this EBAC/CME activity titled “Navigating Rapid Changes in First- and Later-Line Treatment of EGFR-Mutated NSCLC: A Practical Framework for Optimal Biomarker Testing, Treatment Selection and Sequencing, and Adverse Event Management.” For the full presentation, downloadable Practice Aids, and complete EBAC/CME information, and to apply for credit, please visit us at https://bit.ly/49q5M4w. EBAC/CME credit will be available until October 6, 2025.

1. Navigating Rapid Changes in First- and Later-Line
Treatment of EGFR-Mutated NSCLC

A Practical Framework for Optimal Biomarker Testing, Treatment
Selection and Sequencing, and Adverse Event Management

Natasha B. Leighl, MD, MMSc, FRCPC, FASCO

Lung Site Lead, Medical Oncology

Princess Margaret Cancer Centre

OSI Pharmaceuticals Foundation Chair, PMC Foundation
Professor, Department of Medicine, University of Toronto
Adjunct Professor, IHPME, Dalla Lana School of Public Health
Toronto, Ontario, Canada

Luis Paz-Ares, MD, PhD Joshua Sabari, MD

Chair, Medical Oncology Department Assistant Professor of Medicine
Hospital Universitario 12 de Octubre NYU Langone Health
Associate Professor Perimutter Cancer Center
Universidad Complutense de Madrid New York, New York

Head, Lung Cancer Unit Bi

CNIO (Spanish National Cancer Research Center) 3

Madrid, Spain

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

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2. 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

Enhance your ability to implement biomarker testing
to identify patients with different EGFR mutations in
advanced NSCLC

Equip you with skills for selection and sequencing of
different therapies and combinations in advanced
EGFR-mutated NSCLC

Copyrial

3. Best Practices for Biomarker Testing to
Identify All EGFR Mutation Subtypes

Natasha B. Leighl, MD, MMSc, FRCPC, FASCO

Lung Site Lead, Medical Oncology

Princess Margaret Cancer Centre

OSI Pharmaceuticals Foundation Chair, PMC Foundation

Professor, Department of Medicine, University of Toronto
"Adjunct Professor, IHPME, Dalla Lana School of Public Health

Toronto, Ontario, Canada

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4. Optimal Bi rker Testing Matters: Single Gene vs NGS

Guidelines (NCCN, ESMO, ASCO, IASLC/CAP/AMP)
recommend broad molecular profiling (NGS panels) in
advanced NSCLC, emerging in early-stage NSCLC

SINGLE-GENE TECHNIQUES EMERGING TECHNIQUES

Imimunonistochemistiy IHC) Next-generation sequencing (NES) Multi-omlc assays

. panel Proteome
Fluorescence and chromogenic + Small panel (<50 genes) + Transcriptome
in situ hybridization (FISH/CISH) x Lego panel Ad sens + Meitiylome.

Microsatellite instability (MSI) RNA sequencing (RNASeq) + Metabolome
+ Targeted RNAS: + Microbiome
Polymerase chain reaction (PCR) : rae 2)

Use of Al—predictive, diagnostic
Whole-exome sequencing (WES)

. Signatures, spatial assays, single-cell
Whole-genome sequencing (WGS) analysis, liquid biopsy (exosomes)...
ors tal one 2070128 2 aan CES 3 NEO en Pen CONS alae

Version 8.2024. Insc.pdl 4. Mosele etal. Ann Oncol 2024;35:586:606. 5. Jalyesin et al. J Cln Oncol
BizaZete22 6 Lncomen etal Meme Ono! 201615320388

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5. Gaps Remain in Testing... MYLUNG Study Update’

Availability of Biomarker Testing Results AE AA
atients in Advanced Cohor ith Any
Before 1L Treatment Bicmarker Tesing

Results Prior to 1L Treatment (N = 461)

o 54.6
225 0 A ALK test, n (%) 355 (77.0)
HE i 7 Por BRAF test, n (96) 335 (72.7)
E
3 HE EGFR test, n (%)° 374 (805)
FE
€ E gl KRAS test, n (26? 294 (63.8)
832°
SEE vw MET test, n (%)* 328 (71.1)
o NTRK test, 253 (54.9)
Protocol 1 Protocol 2 near € )
2018-2020 2020-2022 O En
Denomir : protocol 1, N = 3,474; protocol 2, N = 555
peer ner a SA RETest n(%) 305 (66.2)
ROS test, n (%)? 344 (74.6)

+ Denominator: patients wth iomarkr testing ess priori HL treatment ARAS esting i approved for torno ciment 5
1 Evangeist Metal ASCO 2023. Abstract 0109 PeerView

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6. Barriers to Testing in Advanced and Early-Stage NSCLC"

Reasons Biomarker Testing Results
Were Not Available Prior to Treatment

Number of patients who did not receive any

biomarker testing results prior to treatment er
Clinical deterioration, n (22% 561
Barriers to test ordering, n (4) 42(424)
Sampleñissue retieval* E
AO 28 (66.7)
Patientprovder knowledge about is
‚marker testing options“
Payor coverage, financial barriers 124
Other bariers® 9214)
Other reasons, n (2) 53 (53.4)

+ Denominator: patents without biomas
a not have biomarker testing results due o "armer 1 est order”
1. Evangelist Metal. ASCO 2023, Abstract 9108.

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10 (10.6)
24(255)
6 (25.0)

13 (54.2)

3(125)

2(83)
31125)
60 (63.8)

Don't miss the IASLC 2024 Update on
Molecular Testing Global Survey

Smeltzer et al OA 03.03

tosting sut porto treatment. > More than one reason could be selcted. More than one barrer could selectos. Denominator: patents who

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7. sue AND Liquid Biopsy

Liquid Biopsy in Advanced NSCLC (2021 IASLC Consensus)!

-¿2D uE + Paty
re Et pio sx. E
i = biomarkers:
2 POL ease
I - e
| - @- ue

oo TER ren

‘Sequential Complementary Plasma First
(when tissue fails) {nie testo and guie) (when biopsy not possible, delayed) (Treatment Resistance

1. Roto et a. Tome Once, 202116: 1647-1062 PeerView

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8. Liquid Biopsy Can Help Get to the Right Treatment in Time! Now Recommended

by IASLC, NCCN, Including Complementary Testing, ESMO, ASCO17

Minos MT+PNGS

Difference, 59.6

3

sw 798
(186/233)
w ors
A
~ 3
a 3 0m
5
»
8 0%
A
Not prior to AL.
wo} 202 >
(47/233) D 6 2 © à
»
Time, mo
1 No. at Rak
Promo iL 20200 14 9 42
o Ropero 68 2 M Zu

‘Comprehensive Testing
Prior to AL (n = 233)

4. AggamalC et al. JCO Precis Oncol.
5 Pascual et al Ann Oncol 2022:33:750-168. 6. NCCN Clica!
ps Jun nccn org professionalsphysician_lspdlínscl pt. 7. ChakravrtyD et al. J Clin Oncol 2022:40:1231-1258.

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Prior to 1L

o
2 0

Adding plasma ctDNA NGS

+ Higher rates of complete
genotyping

+ Greater opportunity for
precision therapy

+ System impact—fewer
repeat biopsies, faster
time to treatment

323 DIET 2 Ere et a TAM 202.3, Gavia et ak TAM 2024 Rolo et ad Trae Ql, 202116147 1682
Practice Guidlines in Oncology. Non-Smal Cll Lung Cancer. Version 8.

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9. Does Molecular Result Timing Matter?!

Compromised Outcomes in Stage IV NSCLC With Actionable Mutations
Initially Treated Without Tyrosine Kinase Inhibitors:
A Retrospective Analysis of Real-World Data

os

10

os
z Group A
3 os
3 then not switched
ae within 35 days
£ Group 8

id Group C Group ©

o (es

5 D a oa +
Follow-Up Duration; mo. lp 28.8 (23.3-34.6) 217(122-NR) 15.3(11.8-19.7) 16.5(12.2-21.7)
No, at Risk (95% ci
À M 26 ne 4 o HR Reference 112 102 127
8 4 a sa 1
e #4 4 20 7 o E _ 5 sd 7,
1. Scott JA eta. J Oncol Pract 2024:20:145-183. PeerView

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10. Sequence of Therapy Matters!

Retrospective Analysis of Patients With EGFRmut Interstitial Lung Disease (ILD)
NSCLC Who Received Immunotherapy and TKI' in the TATTON Trial?
© © © patients received immunotherapy first Treatment LD
+ 15% experienced severe irAE(s)
+ IFTKI given within 3 months of 2.9% (35/1205
immunotherapy, risk = 24% Osimertinib monotherapy grade 3/4: 14;
+ Among six patients who developed severe grade 5: 4)
irAE(s): four cases of grade 3 pneumonitis,
one grade 3 colitis, and one grade 4 hepatitis
2.0% (23/1149;
N th ide 3/4;
... Durvalumab monotherapy Cr
Patients received TKI before
immunotherapy
a: re 38% (13/34;
BIER ck severe MON Osimertinib + durvalumab grade 34: 5;
grade 5: 0)
1.Schoenfe Ale. Ann Oncol. 201930183944. 2, An A et al ELCC 2016, Abstract 1960. PeerView

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11. Testing: EGFR and Beyond!

Gui

es (NCCN) Recommend Broad Molec!

Comprehensive profiling (NGS)

+ Best for detecting rare variants
and complex alterations in multiple
genes in a single assay

PCR-based assays

+ Fewer alterations assayed

+ Can detect most common variants
(L858R, ex19 del)

+ Fast TAT, less DNA required

1. Provided courtesy of Lauren L Riterhouse, MO, PhO. PeerView

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12. EGFR Exo Insertions

+ 4% to 10% of all EGFR-mutant NSCLC
— This could be limited by testing type

+ First/second-generation EGFR TKIs have
limited activity

= ini inib: y 33d 3853373938
Erlotinib/gefitinib: mPFS, 1.5-2 mo 355 i ag i] $3 i H ¿ ei
- Afatinib: mPFS, 2.9 mo EERE EAS fF
5 ge 53 E
+ Worse prognosis than other types of ES
EGFR-mutant NSCLC no
Re

1. vyse 8. Huang PH. Sra Transdet Target Ther, 201885. 2. Yasıca He al. Si Trans Med, 2018521818177, PeerView

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13. Exon20ins Variants Identified
From GENIE

1m Not detected by commercial PCR kits

BRS

= 25:
5 2.
15

Number of Patients

o
E AN
LOE EEE
BEL SES’ SSL SLO
+ Patients with exon20ins detected by

- PCR=89

— NGS = 175

— PCR misses 49.1% of cases identified by NGS
À MEL amaia

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Exon20ins Variants Identified
From Foundationinsights

160, * Nol detected by commercial PCR kts

o "A

AS

+ Patients with exon20ins detected by

- PCR = 305
— NGS = 627
— PCR misses 51.4% of cases identified by NGS

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14. Necessary arker Testing for Lung Cancer in 2024

+ Complete biomarker testing prior to therapy is needed to optimize care

+ PD-L1 tumor expression, genomic alterations (EGFR, ALK, ROS1, BRAF,
NTRK, MET, RET, KRAS, ERBB2)

+ Guides initial therapy in advanced nonsquamous NSCLC and now in earlier
stages of disease (PD-L1, EGFR, ALK)

+ Type of testing matters (NGS, DNA vs RNA)

+ Interpretation of results is just as important
— Know what you're looking for (mutation vs amplification/overexpression)
— EGFR or biomarker “positive” is not enough > more granularity needed

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15. A Case to Consider

Patient History and Presentation

A 63-year-old woman presents with dyspnea

Workup > pleural effusion

Pleural fluid cytology positive for adenocarcinoma of lung

PET scan: multiple bilateral pulmonary nodules

Biomarker testing reveals EGFR exon 21 L858R mutation; PD-L1 TPS <1%
ECOG PS 1

Comes to your clinic to discuss the biomarker testing results and first-line
treatment options

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16. Considerations for Selection and
Sequencing of EGFR-Targeted Therapies
Throughout the Advanced EGFR-Mutated
NSCLC Disease Continuum

Luis Paz-Ares, MD, PhD

Chair, Medical Oncology Department

Hospital Universitario 12 de Octubre

Associate Professor

Universidad Complutense de Madrid

Head, Lung Cancer Unit

CNIO (Spanish National Cancer Research Center)
Madrid, Spain

Copyright © 2000-202

17. FLAURA: Phase 3 Study of First-Line Osimertinib in

EGFRmut Advanced NSCLC"

Best Change From Baseline in Target Lesions
Osimertinib

os

moS.mo
(ose eh

CET ET]
Comparto EGFR TI 31.8(266-960)

Gefitinib or Erlotinib

‘comport EDER TH

NENE TE TETERA
Nami Time Since Randomization, mo.

Songer 277 363 22 zz zo un ns O HoH m a D 2 €
reve

Bost Change From Baseline, % Best Change From Baseline, %

1. Soca at. Engl J Mod. 2010:78:113-125.2. Ramalingam SS eta. N Eng Mad. 2020;3824-60, PeerView

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18. FLAURA2: Phase 3 Study of First-Line Osimertinib +

Chemotherapy in EGFRmut Advanced NSCLC13

First-Line Osimertinib + Platinum-Pemetrexed in EGFRmut Advanced NSCLC

Follow-Up
+ RECIST 1.1 assessment
atweeks 6 and 1
every 12 weeks until (OP
or other withdrawal criteria

80 mg QD + pemetrexed
5 n? + carboplatin AUC

cisplatin 75 mg/m 4
followed by maintenance osimertinib

Patients with untreated, EGFRmut advanced NSCLC

mg QD + pemetrexed Q3W el
+ Aged 218 years (Japan 220 years) a + Brain imaging mandatory
Pathologically confirmed nonsquamous NSCLC alboselno and

Ex18del or LBSÖR (local/central test)
WHO PS 0-1
No prior systemic therapy for advanced NSCLC

progression forall patients
and at scheduled
assessments untl
progression for patients
with baseline CNS mets

Osimertinib 80 mg PO QD

+ AIICNS scans assessed
+ Primary endpoint: PFS by investigator assessment by neuroradiologist CNS
per RECIST 1.102 BICR using modified

RECIST guidance
+ Key secondary endpoints: OS, ORR, DOR, DCR, HRQOL, safety (AEs by CTCAE v5), PFS2°

«Patients wih asymptomatic CNS mets (not requrng steroids) or wth a stable neurological st
‘lowed. * Pemevexed maintenance continued uni a dacortinuation crieren was met « Efficacy
‘comparison between treatment arms was regardless ofthe treatment actualy received. The safety

22 weeks ater conplton of def aiment and tks, recae, were
ss wore inthe hl analy set. ined asa patera rancomice o sit

as at was dened as ol ondomzed pats who veceved > cos ol ty

Testment on pater! who was ardornze a oemerini ls patna pereveed ocewed ony ormers an was aie ned ito serait moncmerapy sae amar at
{The study provided 90% power lo demente à sacialy giant ciferance in PFS ascumn HR CB at Se wo Sd sgnficance oval 7

Y Panchard Det al ESO 2023. Abstract LADO, 2 hp rats govlstidyNCTOAO9S4EE, 3, Plancha D etal N Engl J Med. 2023-288 135-1948, PeerView

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19. n EGFRmut Advanced NSCI Ce

PFS per Investigator Assessment

10
go
E
Eos Osimerind + chamo.
2
Cary)
Eo A
o + +
os 6 5 2 6 6 À À 7 E à à
‘Time Since Randomization, mo

cb me arom om ue Mot

er A A à à .
Pme ot MEL 2023. Abaroct PLOG 13 2. Plancha Det al ESMO 2023 Abstract LBABS. 3 Plancha D tal. 1 En J Mec. 2028380 1996-988. PeerView

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20. FLAURA2: PFS With First-Line Osimertinib + Che:

n EGFRmut Adva

PES Among Patents.
With CNS Metastases at BL

es ‘Osimertinib +
gy platinum pemetrexed an
PFS per Investigator Assessment € nn porras RENO)
e EEE =
jo en Time Since Randomization, mo
po oumorinb scene = nw wea os te
É a PES Among Patients
¢ Without CNS Metastases at BL
a 02 a
en Osimertinib + da
3 ES platinum pemetrexed “gre
oT tthe en E ZE BEE) E a en
“Time Since Randomization, mo ge da]
ue a uses (067-305)
Slice vases: Fe mone pe
momen om om men PUTT Tea aT eee
sa. Timo Since Randomization, mo
en SScessense ah:
‘anne Pet. WCLC 2025. Abstract PLOS.1S. 2 Planchard Det al ESMO 2025. Abstract LBABB. 3. Pianchard Dell Engl J Med. 2025/89: 1935-1088 PeerView

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21. FLAURA2: Adverse Events!

Osimertbib + Platinum-Pemetrexed (N

276)

Any Gradi

(Osimertbib Monotherapy

‘Anemia
Diarthea

Nausea

Decreased appetite
Constipation

Rash

Fatigue

Vomiting

Stomatis

Neutropenia

Paronyenia

Neutrophil count decrease
covo-19

AT intense

Platelet count decrease
‘Thrombocytopenia

Dry skin

AST increase

Blood creatinine increase
Whtecel count decrease
Peripheral edema,

128 46)
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81 (29)
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76 28)
73 (26)
68 25)
68 (25)
65 (24)
6202)
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56 (20)
51 (18)
51 (18)
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4817)
sum
44110)
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85 (30)
81 (29)
49 (18)
60 (22)
55 (20)
45(16)
50 (18)
40(14)
40
28 (0)
5@)
20
26119)
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43 06)
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43 (16)
28 (11)
34 (12)
28 (10)
2007)
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27 (0)
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su
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‚Jane Pet a. WCLC 2023, Abstract PLO9.19.2. Planchard D etal. ESMO 2023. Abstract LBAB. 3. Planchard D et al. N Eng! Mod. 2023,389:1935-1948 'eerView
ALO REC Peer
1 3 y 4100 Vi

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22. MARIPOSA: Phase 3 Study of Amivantamab + Lazertinib

in First-line Treatment in EGFRmut Advanced NSCLC

First-Line Amivantamab + Lazertinib vs Osimertinib

Amivantamab 1,050 mg
first 4 weeks, then every
Lazertinib 240 mg

29; open labe

Serial brain MRIs required
for all patients"

Patients with untreated,
EGFRmut advanced NSCLC

Stratification

+ Treatment-naive for + Ext9del vs L858R
advanced disease nan es erro)
+ Documented EGFR
Ex19del or LESER + History of brain mets®

ECOG PS 0-1 (seu)

Endpoints assessed in amivantamab + lazertinib vs osimertinib arms
+ Primary endpoint: PFS® by BICR per RECIST 1.1
+ Secondary endpoints: OS, ORR, DOR, PFS2, symptomatic PFS, intracranial PFS, safety

+ seine bain URI was required or al patents and peered 28 dys proto randomizton: patents wh coi nt have Ms were atomos ts have CT can. Sain scan requeny
‘ts ever 8 week o o fat 30 mont and then every 12 week rear fr patents wth a lay of bre melasan an ev a eens or patents wath no hao ofan

Trasse. Ecracranl tumor assesoments wre conducedevay 8 weeks forthe rs 90 moths and an every 12 wos cnt esac presta ls confmod by BCR Key sata!
«someto. 000 pants wth 450 PFS events ou provide apronmatey 00% cower fr amivniama + ern ve sierto dee a HR 01073 ang alegan teat wih an
aro sd apa 003 assuming an ncromonil media PFS fF monte) Sita pores osingnauded PPS and non OS «These socondayendscitseymomasc and
‘trocrana PFS) wi bo presented ata tue congress E
‘Cho 80 et ESMO 2023. Abstract LOAYA,2. Cno BC et al. Engl Med. 2024 Jun 26 Epub ahead of pit PeerView

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23. MARIPOSA: PFS With First-Line Amivantamab + Lazertinib

in EGFRmut Advanced NSCLC12

PFS (BICR) Benefit With/Without Brain Mets

Primary Endpoint: PFS by BICR®

ge
‘Amivatama + lazer reduced ie sk of progression or det by 30% ond improved medion PES by 7.1 mo gre EA
#1 »
A ‘Avant +
Manon: 220 m0 HR Fin
w ers nntsscn SE
nz .
ä anne Armen, ETE METETE SS
em ee te) num, mo
20 + a HR [email protected]: P=.001) A
4 H Won Water ot Meca PFS. mo
bo | 4 a meen os er Es
H Osimeninto x EI
a i H sie riens
H H fie oso
o — + 3 Amivantamab +
CTA EN ZEN ie finie
Time, mo =
Pen ge Osimerinib
Siete ay mi a mmm wk
oo wm M me wm ee ENREREEEEEE
fa Time, mo
+ Atte tine of respecie final PES analysis, there were a total of 444 PFS events in the amwvantamab +lazerind Same 2 wig mm mw ee
and uen ame combined.
1. Cho BC et al ESMO 2023, Abstract LOA 2. Co BC et al. N Engl Med 2024 dol: 10.10SONEINGa2403G14 PeerView

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24. MARIPOSA: Interim OS With First-Line Amivantamab

+ Lazertinib in EGFRmut Advanced NSCLC12

Early Survival Data Show a Trend Favoring Amivantamab + Lazertinib vs Osimeı

100
x
EN Amivantamab +
= lazertinib
E
B 60 Osimertinib
2 40
=
É 20
ES
04 +
o 3 6 9 12 1 18 21 24 27 30 33
bass Time, mo
Amivaiama + azorin 429 409 9 2 74 a 21 12 OS #4 0
Osimenind 49 6 m CI

+ Tere wor ata 1 24 dota in amivntama + aren and sine as a era of he prspac nr OS analy, wich oresants 25% of al randomized pots and
55% one "390 presets des forthe tal OS ana Modane sn te sro rei extn.
1, Gho BC etal ESMO 2023 Abstract LBA. 2. Cro BC et aN Engl Me 2024 do 10.1OSE/NEJNoOZA09614, PeerView

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25. CONFERENCE UPDATES 8 HIGHLIGHTS | AWCLC24

Abstract OA02.03

Amivantamab + Lazertinib vs Osimertinib in First-Line EGFR-Mutant Advanced NSCLC:
Longer Follow-Up of the MARIPOSA Study

Presenter: S. Gadgeel

+ After longer follow-up (median: 31.1 mo), data continue to favor firstline amivantamab + lazertinib over osimertinib with a
promising OS trend (HR, 0.77; P = .019) in patients with EGFR-mut advanced NSCLC
OS curves separate early and widen over time, favoring amivantamab + lazertinib
61% of patients receiving amivantamab + lazertinib were alive at 3 years vs 53% for osimertinib
+ First-line amivantamab + lazertinib showed reduced risk of CNS progression and sustained CNS control with more
durable responses
+ 3-year intracranial PFS was doable for amivantamab + lazertinib vs osimertinib (38% vs 18%)
+ Amivantamab + lazertinib showed a favorable trend for intracranial DOR (NE vs 24.4. mo)
+ Post-progression outcomes (TTD, TTST, PFS2) were significantly improved with first-line amivantamab + lazer
vs osimertinib

Amivantamab + lazertinib is FDA approved for first-line EGFR-mut NSCLC and is improving long-term
outcomes vs osimertinib, based on its mult-targeted mechanism and blocking of EGFR and MET with
immune cell-directing activity

‘The MARIPOSA study is ongoing, and a prespecified final OS analysis with formal statistical testing will be conducted in the future:

pyright © 200

26. MARIPOSA: Adverse Events’?

Related to EGFR: Diarthea
inhibition Dermatitis acnelform
Stomatitis

Pruritus

Related to MET. Hypoalbuminemia
inhibition Peripheral edema
IRR

ALT increased

Constipation

AST increased

covib-19

Decreased appetite

Anemia

Nausea

Hypocalcemia

Cough

100

1.Cho BC et al. ESMO 2023. Abstract LBAY4. 2. Cho BC et al. N Engl Med. 2024. do: 10.10SEINEIMoR2403614,

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"

M Ami + lazer: grade 1-2
M Ami + lazer: grade 23
M Osi: grade 1-2
M Osi grace 23

4

Safety profile of
amivantamab + lazertinib
was consistent with prior
reports, mostly grades 1-2

EGFR- and MET-related AES
were higher for amivantamab
+ lazertinib except diarrhea,
which was higher for
osimertinib

Incidence of grade 4-5 AEs
was low and comparable
between arms

Rates of ILD/pneumonitis
remained low, at ~3% for
both arms

E

Percent

mo

PeerView

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27. Baseline ctDNA: Prognostic and Predictive

A Clearance: Prognostic and Predi:
Co-mutations as a Prognostic Biomarker! MARIPOSA: Can We Use TP53 Status to Select

Patients for Upfront Combination Therapy?2

CE
CE

»

Amivantamab +
taxer

Mutation Frequency, %

er

É
Él

LAB ARIDIA BRCAT HF1 PTEN]SMADA ATM STK11 COKNZA si”
y

pos
o
pi EN

+ Co-mutations in TP53 and tumor suppressor
genes are associated with worse TKI outcomes

1. Stocthammer etal. J Thorac Oncol, 2024 Feb: 19:240-251. 2 Felip E etal. ASCO 2024. Abstract 8504

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28. PALOMA-2: Amivantamab in First-Line Advanced or Metastatic

Solid Tumors, Including EGFRmut NSCLC"

‘Safety

+ Aside from markedly lower rates of ARRs and VTE, the safety profile of SC amivantamab + lazerinib was consistent with what was previously reported with IV
‘amivantamab + lazertnib, with no new safety signals identified

~ Discontinuation of all agents due to TRAES occurred in 9% (11/125) of patients

ARRs were reported by 15% (19/125) of patients.

- The majority of ARRS (n = 18/20; 90%) occurred in Cycle 1 (on or after C1D1 but before the next dose; one patient experienced two ARRS [one on C1D1 and one on
c109)

— Median time to ARR onset was 2.3 hours (range, 0.3-7.2)

= The rate was lower compared withthe rate with IV
‘administration in MARIPOSA (63%)

iy EE
Associated win EGFR inion
+ Among al patient, the INV-assessed ORR was 77% "Std wm 20 Mm 26 m 40
and the ICR-assessed ORR was 79% Rash 48 (71) 913) 28 (49) 34) 76461) 12(10)
+ A similar BICR-assessed ORR of 86% (95% Cl, 93-89) crane ¿corel A 63} ooo) HA 19 E] fl am
as observed with IV amivantamab > zer in rus €
Stomatitis DES) 3m) 1@ SUN 40
MARIPOSA Diarthea 16 (24) 0 ra) 18 28122) 11)
+ Among confimed responders in both cohorts AE
= Median TTR was 1.9 months (range, 1.453) poa mem HE) 3@ au 0 mms
ken DOr ven asinine! Peripheral edema 26) 10 E ZU
increased ALT am 0 aN) 46) 8)
head AST ES 416) 5)
Races jee) 0 eg 0 46%) 0
CT 3
we) 10 BEN
ORR. 75 zn Bit 0 ME) 0 269 0
BEC) was goss) (6590) (1er (6880) POE) won 0 sm 0 zu o
1.LIMSMetal ASCO 2024 PeerView

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29. CONFERENCE UPDATES 8 HIGHLIGHTS | #WCLC24

SKIPPirr Study Design

u Pinar pit een a rg C18
+ EOER tron 100 san worse NSCLC Seca see
‘eer a penca comer oes Here

Es Key inclusion ctra
+ Front pers
=~] ‘wth EOFRm SCLC

Loc sons

— AN een (Gage 8c ce

TAS Ban + rermetemator
zur Dres ro
And sa bran

+ ecoseso1

palmar (rt
25 pa ue ones

resulted in a ~3-fold reduction in IRR incidence (67.4% to 22.5%) vs
standard management; pts experienced fewer IRR-related symptoms.

iew.com/EQU827

US, EU, LATAM, APAC.

N=18

Amivantamab + lazertinib + SOC dermatologic
management (n= 90)

Copyright © 2000-2024, PeerView

30. Returning to Our Case and Panel Discussion PA

Let's Discuss
Patient History and Presentation 0
How do we select among the different

A 63-year-old woman presents with dyspnea iL een epten and what are the
Workup > pleural effusion + een een
; iti i at it ¡e patient ha rain
nn fluid cytology positive for adenocarcinoma metastases or high PD-L1 status?
PET scan: multiple bilateral pulmonary nodules ae pit al

lection?
Biomarker testing reveals EGFR exon 21 L858R treatment se ection
mutation; PD-L1 TPS <1% What if the patient develops IRR?

ECOG PS 1 What would you do for prophylaxis and

a management?
Comes to your clinic to discuss the biomarker

a 3 What if the patient devel
testing results and first-line treatment options dermatologlc AES? ee you

manage them?

Copyright © 2000-2024, PeerView

31. Variation on Our Case

Patient History and Presentation

| A 63-year-old woman presents with dyspnea
Workup > pleural effusion
Pleural fluid cytology positive for adenocarcinoma of lung
PET scan: multiple bilateral pulmonary nodules
Initial biomarker testing reveals EGFR exon 21 L858R mutation; PD-L1 TPS <1%

Started on 1L osimertinib, but after 12 months, patient’s repeat imaging shows
pulmonary, liver, and bone metastases

Remains asymptomatic

ECOG PSis1

Repeat biomarker testing shows no new targetable alterations
Comes to your clinic to discuss options for further therapy

Copyright © 2000-2024, PeerView

32. Mechanisms of Resistance to First-Line Osimertinib*3

Frequency Freqi

Mechanism Aeration Frequency, Froqu Treatment
Cros 15% 3%7% gen EGER TKI
On target EGFRamp 11% TH ts/2nd-gen EGER TK
724s, L7iev CE EGFR antibody
Osimenini + MET
inhibitor
ff target METamp 1% 10%-15% Osimarin + ALK
(vataton, ALK fusion 2% 2 inhibitor
drug avaiable) BRAF,HER2, RET 010% 247% Ouimerinib with MET,
BRAF, RET inhibitor,
TOMTE
er 15% 015%
NO tmp IR ae
off target CONETamp dh 0% Standard chemotherapy,
(no validation, ARAFamp x E ‘cinical trials
no drug) MYCamp, (amiflazer, HER3-DXd)
MDMZamp, CDK4A
PIK3CA, KRAS es LEE
Sauamoustemal CS Ynknoım
transformation. E
Lineage plastciy ansfermatk 9% 15% Taïored chemotherapy
EMT, AXL upregulation > 20
Standard chemotherapy.
Unknown None on NGS 0% ~45% clinical als
(amitazer HERS.DXS
Y Sehoefels Aleta Gn Cancer Res. 2020728 2694-2069, 2, Rumalnga SS ell JG Ona. 207836848493 Fue povided couresy of Hera À Yu O. PeerView

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33. MARIPOSA-2: Amivantamab + Chemo + Lazertinib vs Chemo in
EGFRmut Adv NSCLC After Progression on Osimertinib12

n September 19, 2024, the FDA approved amivantamab with carboplatin and pemetrexed for patients with locally advanced or metastatic NSCLC
with EGFR exon 19 deletions or exon 21 L858R subs!

Amivantamab + chemo + lazertinib vs chemo in EGFRmut advanced NSCLC after progression on osimertinib

Serial brain MRIs required
Patients with EGFRmut for all patients® ‘Amivantamab + lazertinib + Dosing (21-Day Cycles)
advanced NSCLC Y: Amivantamab: 1,400 mg for frst
+ Documented EGFR a, “4 weeks, then 1,750 mg every 3

‘weeks string at week 7
ex18del or LBSSR = Osimerinib line of Lazorini: 240 mg QD saring

+ Progressed on or aftor therapy (‘st vs 2nd) Chemotherapy ‘ater completing carbopate?
AO Asia re Ge or a) (n= 263) ‘Chamotharapy at beginning of
(as most recent ine) : every oye

+ ECOG PS 041 elos of brain met) + Carboplatin: AUCS fr fst

(yes or no) four eyes

+ Stable brain mets Amivantamab + rd:
ne resent wes en ee
not required isa progression

Endpoints assessed in amivantamab + lazertinib + chemotherapy vs chemotherapy and amivantamab + chemotherapy vs chemotherapy arms
+ Dual primary endpoint: PFS® by BICR per RECIST 1.1
+ Secondary endpoints: ORR. DoR, OS; intracranial PFS, time to subsequent therapy,* PFS2,* symptomatic PFS,* safety

Patents who cous not have MR were slowed to have CT scans,» Al patents randomize before November 7,202, has atra onthe rt day of Cycle . Kay static!
‘ssumpions 600 patos wa 350 overs across al ara woul prov approxmato) 89% and 09% power for amvantamab-cvemoheepy and amwrenamab lazerinbschemeihergy.
‘especialy ve chemesherapy o detecta HR of 055 ving alogank test win an oval no-cd alpha 08 (nadan PFS of 85 monts fo amivaamab-conaning arms vs 5 lor
‘hemainergy). Saisie hyphae tostng iced PFS, ORR, ana thon OS. Thess socondary endpents (im o sogen heaps, PFS2 ar sympomste PFS) wl be presented at
‘Tite congress 3

Y Passo A et al, ESMO 2023. Abstract LBA1S. 2. Passar A el Annals of Oncology. 2024:35 77.0. PeerView

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34. MARIPOSA-2: PFS With Amivantamab + Chemo + Lazertinib

in EGFRmut Advanced NSCLC After Osimertinib*?

+ Ata median follow-up of 8.7 months, amivantamab + chemotherapy and amivantamab + lazertinib + chemotherapy reduced
the risk of progression of death by 52% and 56%, respectively

PFS by BICR
Amivantamab + chemotherapy | Amivantamab +lazertinib +
100 versus chemotherapy chemotherapy? versus chemotherapy
Modan PFS: 6.3 versus 42 mo. Medan PFS: 8.3 versus 42 mo

arg
(os 036088)

37 Amivantamab «lazo
chemotherapy

Amivantamab

¿notaras
o
o 3 6 9 12 15 1 Consistent PFS benefit by
PE Time, mo investigator: HR, 0.41 (8.2
Foon Lo ” » a 7 o o versus 4.2 mo; P < .001°)
Ame + and HR, 0.38 (8.3 versus 4.2
== mm ‘ . A!
A ss . o D
+ Amivariamad + azo + chomoterapy am neues a patents regardes of acosa regimen received.
* Nominal Polos andpoat nat pa of racial hype stg .
1. PastaroA ot al. ESMO 2023 Abstract LBA15.2. Passar À ta. Ann Oncol. 2026:35:77-90 PeerView

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35. ial PFS With Amivantamab + Chemo +

After Osimertinib!

+ Amivantamab-chemotherapy and amivantamab + lazertinib + chemotherapy reduced the risk of intracranial progression
or death by 45% and 42%, respectively

Intracranial PFS by BICR

€

i o

Ê Arteta Chomotaraoy

io H

E H ‘chematheraey Amivantamab-Lazerini-Chemotherany

| »

= 3 y

+ Aniantanabiazertn-hemoterapy am
* Nominal value endpoint not part ral hypothesis est .
1.Passaro A etal ESMO 2023 Abstract LBA1S. 2. Passar At al Am Oncol 20243577-0. PeerView

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36. MARIPOSA-2: Adverse Events?

“Associated with EGFR inhibition
Paronychia
Rash
Stomatitis
Darmea
Associated with MET inhibition
"Hypoalbuminema
Peripheral edema
Associated with chemotherapy
‘Neutropenia
Trrombocytopenia
Anemia
Loukopenia
Other
Infuser-reiats reacton
Nausea
‘Constipation
‘Decreased appatte
Voniing
Fatigue
asthenia
‘Alanine aminotansterase increased

‘AESts by grouped term
‘Rash

vie
no

1. Passaro À et al ESMO 2023. Abstract LBA15. 2 Passaro A etai, Ann Oncol. 024:35:77-90

PeerView.com/EQU827

104) o 4807) 3 13910) ne
126) o 56 (3) 20 128 6) 176)
Br 9 4132) 10) 120 9) 2419)
on 109 1814) 10) 68 (4) 10 (8)
2109) 104 m) 3 104 (5) 126)
1506) 0 4262) 20) 50) 104)

ETE Tr NE EN
72 50) 2290) STA) Mu) sen Won
‘7 0) 20 519) IBN) Te) 48 (18)
68 (28) 20 ve 28620) 1067) men
104) o 76 (8) 70) 148 (ce) so
907) 2a) 56 (49) 10 13160) 160
72 (80) o 50 (38) 10) 9637) am
se) 3) 4061) 0 85 02) 70)

1004) 32 (25) 10 76 (29) 1014)
42 36 (28) 40 69,26) 156)
se) 54 (20) 10 ao) 46)
1048) 26 (20) 79) 55021) 46)

30,12) o wm 1310) a 40()

1166) 10 300) 3@) 1702) 176)
0 o 2) 16 sa sa

+ Amivantamab-containing arms
had higher rates of EGFR- and
MET-related AEs

+ Neutropenia and
‘thrombocytopenia
— Mostly occurred during cycle 1
= Low rates of febrile
neutropenia (2%, 2%, and
8%)
= Low rates of grade 3-4
bleeding (0%, 1%, and 3%)
+ VTE highest in amivantamab-
lazerinib-chemolherapy arm

No grade 5 events
Rates of discontinuation due
to VTE were low (0%, 1%, and
04%)
+ Incidence of ILD was low in all
arms (<3%)

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37. PALOMA-3: SC vs IV Amivantamab (Both in Combination

With Lazertinib) in Refractory EGFRmut Advanced NSCLC12

Key Eligibility Criteria

Locally-advanced or metastatic.
NSCLC

Disease had progressed on or
after osimertinib and platinum-

based CT, irrespective of order

Documented EGFR Ext9del or
LESER

ECOG PS 0-1
N=418

Stratiication
‘Brain metastases (yes vs no)

EGER mutaton typo Ex19d0l vs LASER)

Race (Asian vs pon-Asian)

‘Type fast therapy (osimertnis vs CT)

Study Design

SC Amivantamab + Lazertinib
(n= 206)

‘ong in 28-y yes)
SC amivancamab(cfomalte wan rHuPH20 and
mine by mars cn 1,00 mg (2240 mg 120049)
teak ir Da esd meat an every 2 weeks era

IV ambrantamat” 1,080 mg wey (1.00 ma #280)
or et à most, tan every 2 weeks reer

‘Lazer: 240 mg PO day

Prophylactic anticoagulation
recommended for the first 4 mo
of treatment

PALOMA (NCT05388669) enrolment period; August 2022 to October 2023; data cutof: January 3, 2024.
*SC amivaniamab was coformulated wih MuPH20 ata concentration of 160 mgimL.°C1 for IV: Days 1 o 2 (Say 2 apples to IV spt dose only (380 mg on day 1 and the remainder on day
2.8, 15, and 22; C1 fr SC: Days 1,8, 15, and 22, afer C1 fra: Days 1 and 15 (28-day cjces) «For calculating primary and key secondary outcomes, a sample size of 400 patients was.
‘estimated lo provide 295% power fra 1-aided alpha of 0.05 alocaled o each of the co-primary endpoints and 80% power wil a {sided alpha of 0 025 allocated to ORR. A hierarchical
{esting approach at a 2-sided alpha of 0.05 was used for tho co primary endpoints (noninferory). folowod by ORR (nerinferirty) and PFS (superoniy), witha combined 2sided alpha ot

0.05, +Two defnitons of tho same endpoint wore used as per regional heath aunodiy uidance. Measured between C201 and C2D15 ! Assessed by modified TASO,
1 Leight NB et al ASCO 2028. LBABSOS. 2. Loigh NB ot al. J Gn Oncol 2024 JCOZ401001. del. 10 12007JC0.24 01001 [Epub ahoad of prt)

PeerView.com/EQU827

Co-primary endpoints‘:
(noninferiority); C2 AUC (noninferiority)!

‘Secondary endpoints: ORR (noninferiority);
PFS (superiority); patient satisfaction; safety

Exploratory endpoints: OS

Copyright © 2000-2024, Peerview

PeerView

38. PALOMA-3: SC vs IV Amivantamab (Both in Combination

With Lazertinib) in Refractory EGFRmut Advanced NSCLC12

+ SC amivantamab + lazertinib demonstrated PK and ORR noninferiority to IV amivantamab + lazertinib in patients with
EGFR-mutated advanced NSCLC with disease progression on or after osimertinib and chemotherapy

+ Compared to the IV arm, SC amivantamab also showed
— Numerically longer DOR (11.2 vs 8.3 months) and PFS (6.1 vs 4.3 months)
— Significant improvement in OS (HR = 0.62; nominal P = .02)

SC Amivantamab Arm IV Amivantamab Ar

(= 20 {n = 212)
ORR, % (95% Cl)
Coprimary PK Endpoints Met Noninferiority Criteria Fe 20427) nen
Crougn at C2D1 arme, er Relative risk, 0.92 (0.704.23); P= 001
ria bib ‘DROS Confirmed 27 (21-33) 27 (21-33)
ar Cor) rer responders Relative risk, 0.99 (0.72:136); P<.001
2 ws 3 Best response, n (%)
im = ES 105 109
E = i= PR so) 68 (32)
Pio ES a sD 93 (45) 81 (38)
H = ne Po 37 (18) 42 (20)
in gm NE 147) 20)
Pme ous Res M DCR, % (95% Cl) 75 (69-81) 14 (64-77)
"wm E rs =
ono) ont eo conte) MecleniT7R Favs: 150269 1501299)
1. Legit Ne al ASCO 2024. LBABSOS. 2. Leigh NB tal J Gin Once 2024602401001. [pub head pin} PeerView

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39. PALOMA-3: SC vs IV Amivantamab (Both in Combinatio

+ The safety profile of SC amivantamab was consistent with IV, with fewer IRRs
(13% vs 66%) and VTE (9% vs 14%)
Incidence of IRR-Related Symptoms

ss Rates of VTE by Treatment Arm and Prophylaxis Status
SC Ami IV Ami
Grade m

8 8 8 8

Patient-Reported
Convenience, %.

Hypotens
Sinus tachycardia
Erythema

i
|

n=206 n=210 n = 164 n=171 n=42'n=39

All Patients On Prophylactic No Prophylactic.

hidrosss Anticoagulation Anticoagulation

Hype
Increased hear rate

1. Legit Ne al ASCO 2024. LBABSOS. 2. Leigh NB tal J Gin Once 2024:1C02401001. [pub ahead of pin} PeerView

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40. PALOMA-3: SC vs IV Amivantamab (Both in Combination

With Lazertinib) in Refractory EGFRmut Advanced NSCLC12
Treatment Administration Time and Convenience

+ Treatment administration time was reduced to less than 5 minutes for SC amivantamab from 5 hours for the first
infusion (2 hours for subsequent infusions) for IV amivantamab

+ More patients reported their administration method to be convenient or very convenient with SC vs IV amivantamab

Frequency of Patient-Reported Convenience per Modified TASQ
100 P<.001 P<.001

Patient-Reported
Convenience, %

SC Amivantamab IV Amivantamab SC Amivantamab IV Amivantamad
Am ‘fam Arm Am
(n= 193) (n= 195) (n=61) (n=51)
c1D1 EOT

1. Legit Ne al ASCO 2024. LBABSOS. 2. Leigh NB tal J Gin Once 2024::COZA01001.[Epub head ol pin} PeerView

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41. Amivantamab + Lazertinib in Patients With EGFRmut Lung

Cancer and Active CNS Disease’

NCT04965090
+ Patients with progressive or new brain metastases (BrM) or leptomeningeal disease (LM)

+ All patients with EGFR exon 19 de\/L858R/atypical mutations had prior osimertinib, all patients with EGFR exon 20
insertions (ex20ins) had prior chemotherapy

+ Coprimary endpoints were systemic ORR by RECIST v1.1 and CNS ORR by RANO-BM or LM

BrM Cohort Cohort

‘Systemic ORR (95% Cl) RECIST 30% (13%-54%) 32% (15%-55%)
Intracranial ORR (95% CI) RANO 40% (20% 64%) 23% for LM patients (9%-46%)
Median time on treatment (range), mo 3.9 (0.3-18.6) 8.1 (0-21)

+ Most frequent TRAEs (230% in overall population) were rash (71%), infusion-related reaction (59%),
paronychia (43%), fatigue (40%), edema (40%), mucositis (33%), and nausea (33%)

+ Most frequent (25%) grade 23 TRAEs were infusion related reactions (7%), thromboembolic event (5%),
elevated AST/ALT (5%), and rash (5%)

+ Three patients (7%) discontinued treatment due to TRAEs 2
1. YUHA, etal. ASCO 2026, Abstract 617 PeerView

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42. HERTHENA-Lung01: Clinically Meaningful Efficacy Observed in

the Overall Population and Across Subgroups‘

Subset With ‘CORR by Patient and Disease Characteristics at Study Entry

Prior EGER TKI | prior 3G EGFR N ORR, %

Confirmed Responses aa PoC

and Survival pels TKiandpec a 25 00 +
(n = 209) sy 11 za er
se 265y 104 327 +
CORR, % (95% Cl) 29.8 (23.9-36.2) 29.2 (23.1-35.9) ae Female 132 28.0 re
CR, (%) 10.4) 10.5) Male 93 323 u m)
PR.n(%) 66 (29.3) 60 (28.7) Asin 105 257 m
SD, n (%y 99 (44.0) 91 (43.5) Race ‘White 92 304 me
PO, n(%) 43(19.1) 41 (196) omer 2 429 be
NE, n (9) 467.1) 16 (7.7) EGFRacivatng Ext 142 268 ==
ratelon LESBR 82 354 re
DCR, % (95% CI) 73.8 (67.5-79.4) 72.7 (66.2-78.6) History of rain Yes 118 207 Hea
Peas No 110 209 le
E 3 Pro Yes 9 203 ——
Median DOR, mo (95% Cl) 6.4 (4.9-7.8) 6.4 (5.2-7.8) immunotherapy. No 135 274 Er
prorrgimenstor 2 207 OY
Median PFS, mo (25% Ci) 556159) 556.164) ivan densa, n 2 106 227 Rue
o 0 2% 3% 40 50 60 70
‘Median OS, mo (95% Cl) 119(112-13.1) 11.9 (10.9-13.1)
Confirmed ORR, %
Ses non Sinon PD.» Ko adenume posbaelne tor scene (1 1, 9D oo ed (SO 5 wees aer sa ol uy esten n=)
dedos non CRon-PD ho sun poubassine tar assesument (> 12) SD lo en (SD <5 weeks aer start lucy aiment = e
{YUMA etal WCLE 2025, Abstract ORDS OS PeerView

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43. HERTHENA-Lung01: Tumor Reduction Across Diverse
Mechanisms of EGFR TKI Resistance’?

HER3-DXd 5.6 mg/kg (N = 225)
Confirmed best overall response (BICR)
BOR MPR MSD BPO BNE M

Best Change in SOD (BICR)
From Baseline, %
8258083888

il

2023 Meda study oo p. 189 (ange 4275) no,
ge lesion measurements at both baseline and postbaseino and are includes,

1.YUHA tal WCLE 2023 Abarat 0806.09. 2 Yu HA eta. J Cn neal, 2023;J002301476. PeerView

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44. BL-B01D1-101 FIH Trial!

All Patients Safety of the BL-B01D1-101 Study
ny ‘Al Patents (N= 195), %
ze ORR = 45.3% ‘Median follow-up, mo 41
PR Median tne of price trestment=3 .. TT]
E ‘eatnentdacontnuston 30
Ez Dose reduction 45,25)
gs Rasa vin ath 20
H “0 Grado 23 TRAE am
is Trosmen tos SAE Pr
[er x New lesion. ps cl OO ET
» ‘Leukopenia M1961) 89660)
3 | Anna muss 4005)
Ro» NSCEe: EGERmuty: BOR. Neutropenia 104 (53) 67 (34)
da N=30 WPR MSD MPO *Newiesin RS EEE
ES Nausea 66 1(21)
LE FLE || Voning BEE nono wes
Es ORR = 63.2% LS we NA observed
2 Median ie of rice treatment = 3 Astonia “m 20
Orense appette LS)
Pood Hoth canton ms
re Daten man 16)
== montag zu 0
Rash zu 0 .
1 Zhang Letal ASCO 2025, Abstract 3001. soma zu PeerView

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45. TROPION-Lung05: Phase 2 Study of Dato-DXd in Previously

Treated NSCLC With Actionable Genomic Alterations?

Sage BC, eV NSCLC + Primary engin RR by Efficacy Summary
+ Secondary endpoints:

Wit AL

21 os of tgs therapy
1012 po ata agert-contarirg rap nth
maine sting
Facograhiedaeata progression aña tratos therapy

eon men ame
ge Pia a maa tr ge ken Gea, E Gey
safety Summary, PASA Bai Sm laa un SES bd
TEAES Occuring n215%ot Patents % Medan DOR, a ; ;
‘All Grades (N = 137 É mo.
E da en ae
ES ‘OCR
3 om wen sa
ay oe E EA
pa
Da ado ally ao

+ BOR: In the overall population (n = 137), four patients
(8%) achieved a CR and 45 (33%) achieved a PR.

+ EGFR subset: Among patients with sensitizing or
‘T790M mutations (n = 68), the ORR was 49.1% in
those previously treated with osimertinio

Fine

+ Te pay complton dto wil ocur when a patate have had ara minimum ef 9 enh ooo ar ro sao dy treatment
Srna dach fem thes. .
Paz AS Letal ESNO 2023, Abstract 1941M0, PeerView

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46. CONFERENCE U e aweve2s

Selection of Other Studies Presented at IASLC WCLC 2024

MA12.07: Amivantamab Plus Lazertinib vs Osimertinib in First-Line, EGFR-Mutant Advanced NSCLC:
Patient-Relevant Outcomes From MARIPOSA, D. Nguyen

+ For patients with treatment-naive EGFR-mutant advanced NSCLC, amivantamab + lazertinib significantly delayed
symptomatic progression vs osimertinib, while maintaining health-related quality of life

0A02.05: Lazertinib vs Osimertinib in First-Line EGFR-Mutant Advanced NSCLC: A Randomized, Double-Blind,
Exploratory Analysis From MARIPOSA, S-H. Lee

Lazertinib demonstrated comparable efficacy versus osimertinib across all clinical endpoints, including in high-risk
subgroups

Safety profiles of both lazertinib and osimertinib included mostly grade 1-2 AEs with low and comparable

rates of treatment-related discontinuations

Consistent with lazertinib's suitable combinabilty profile, key safety distinctions between lazertinib and
osimertinib include

— Lower rates of diarrhea, thrombocytopenia, and neutropenia with lazertinib

—Higher rates of rash, muscle spasms, and paresthesia with lazertinib

— Lower rates of QT interval prolongation and cardiomyopathy with lazertinib

OA09.05: Subcutaneous vs Intravenous Amivantamab: Patient Satisfaction and Resource Utilization Results
from the PALOMA-3 Study, M. Alexander

+ SC administration simplifies the delivery of amivantamab, reduces healthcare burden, and is preferred by patients

Copyright © 2000-2024, PeerView

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47. Returning to Our Case and Panel Discussion

Patient History and Presentation

A 63-year-old woman presents with dyspnea
Workup > pleural effusion
Pleural fluid cytology positive for adenocarcinoma of lung
PET scan: multiple bilateral pulmonary nodules

Initial biomarker testing reveals EGFR exon 21 L858R Let's Di
mutation; PD-L1 TPS <1% et's Discuss

Started on 1L osimertinib, but after 12 months, patients | Y How do we select among the
repeat imaging shows pulmonary, liver, and bone different 2L treatment options, and

ns E what are the considerations?
Remains asymptomatic

ECOG PSis 1

Repeat biomarker testing shows no new targetable
alterations

Comes to your clinic to discuss options for further therapy

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48. Another Variation on Our Case

Patient History and Presentation

A 63-year-old woman presents with dyspnea i DNA or
Workup > pleural effusion Aron A Su ees
pe fluid cytology positive for adenocarcinoma ary 24240 497

jung

PET scan: multiple bilateral pulmonary nodules ase 14
ECOG PS 1
Liquid biopsy revealed an EGFR mutation SNS REIN, = u
(see) results in the table) . Sri AL 04 valent area
Tissue NGS from the resection sample showed significance
the same findings FGFR2G103S 0.1 Variant of uncertain
PD-L1 TPS <1% an

Comes to your clinic to discuss the biomarker testing results and treatment options

Copyright © 2000-2024, PeerView

49. Making the Most of the Latest Treatment
Progress in Advanced NSCLC With EGFR
Exon 20 Insertion Mutations

Joshua Sabari, MD

Assistant Professor of Medicine
NYU Langone Health
Perlmutter Cancer Center

New York, New York

Copyright © 2000-2024, PeerView

50. PAPILLON: 1L EGFR Exon 20 Insertion-Mutated

Advanced NSCLC (Phase 3 Study)!

First-Line Amivantamab + Chemotherapy vs Chemotherapy
in EGFR Exon 20 Insertion-Mutated Advanced NSCLC

Dosing (21-Day Cycles)

LEURS Amivantamab: 1,400 mg for fest

chemotherapy A weeks, then 1,750 mg every 3
Stratification weeks starting al week 7
Beco ‘Chemotherapy at beginning of
History of brain mets? every cyel
+ Carboplatin: AUCS for fist
CR Prior EGFR TKI uses four cyctes

+ Pemetrexed: 500 mg/m? until
disease progression

mutations emotherapy
ECOG PS 0-1

go!

+ Primary endpoint: PFS by BICR per RECIST 1.1°
+ Secondary endpoints: ORR’, DOR, OS*, PFS2, symptomatic PFS*, time to subsequent therapy”, safety

+ Removed as sro factor since only ou patients had pr EGFR TKI use (il monetherapy win common EGFR TKis was alowed lack ol response was documented), Patents
‘wth brain metastases wore ell I hey eceved dove besten and were asmplonal cinealy bl, an of orcos animent or 22 weeks prt randomlaton Key
Hasta! assump: 300 patents wi 200 events needed for 90% power o detect on HR ol 0.525 estate PFS of vs months) PFS, ORR. and en OS were incudod in Merril
losing nue secondary endpoints (te o cubeoguan:Iharapy and sera progresse sural) vi psanted at a kare cores. Crossoner was ny alowed tr BIGR
emo 0 seas ogress: amvantamab montherapyon CN dss para dy Ñ

1 Grand N et al ESMO 2023, Abstract LAS. PeerView

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51. PAPILLON: Efficacy of First-Line Amivantamab + Chemo

in EGFR Exon 20 Insertion-Mutated Advanced NSCLC‘

Primary Endpoint: PFS by BICR
Amvontamab + chomotherapy reduced risk a progression or dat by 60%

100 ean ows 149 mo
san PES, mo (9% C2)
la Tariana A MAREA
nero enero
5 ROSS 05% C1.02005%P<-0001,
Lo h a
2 A nm” Chemotherapy
» H Heroes
A H emomnerapf
D I 6 o 2 © © À à
num Time, mo

Conssten PFS benef by investit: 12. versus 6.9 mo (HR. 0.38 05% Cl, 0224.51: P< 00019)

+ Amivantamab + chemotherapy significantly improved PFS vs chemo in first-ine EGFR ex20ins advanced NSCLC (HR, 0.395; P < .0001)

+ In addition, 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; longer PFS2, supporting the first-line 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 treatmentrelated discontinuations with
amivantamab (7%)

«Nominal vale; ercpont not par ol herarcicalhypobsls teng. .
4. Gran N etal ESMO 2025, Abstract LAS. PeerView

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52. CONFERENCE UPDATES 8 HIGHLIGHTS | #WCLC24

ites pias and ctDNA Clearance Among Patients With

+ Amivantamab-chemotherapy demonstrated superior treatment outcomes vs chemotherapy
alone across biomarkers of high-risk disease
- Detectable ctDNA at baseline (HR, 0.38; P < .0001)
- Detectable ctDNA after 6 weeks of treatment (HR, 0.55; P = .098)
- Presence of TP53 co-mutations (HR, 0.29; P < .001)
- The improvement of PFS with amivantamab-chemotherapy was consistent across
subgroups by region of Ex20ins

Amivantamab-chemotherapy is the new first-line standard of care for patients with
treatment-naive, EGFR Ex20ins-mutated advanced NSCLC

Copyright © 2000-2024, PeerView

53. CHRYSALIS: Amivantamab in Pretreated

EGFR Exon 20 Insertion-Mutated Advanced NSCLC‘

Exon20ins location
N=00 m Hoteal region (762.766)

EGFR Exon 20 z ae,
i = 1 Near loop region (7677
sion z à Far on 7379)
Platinum a 1 Roi detectas by ZONA
(N= 81) 2
‘ORR (IRC) 40% 7
mDOR (INV) 11.1 mo 2
mPFS (IRC) 8.3 mo :
Key toxicities
+ Infusion-related reactions (66% any grade, ff
3% grade 23); most commonly on C1D1 SSS = -
* Ra (sig) ee Me grade 29) ME Ea
paronychia (45%) E

+ MET related: hypoalbuminemia (27%), edema (18%)
+ Dose reduction: 13%; dose discontinuation: 4%

1. Park Ket. J Cio Ones 2021:39:3091-402. PeerView

PeerView.com/EQU827 Copyright © 2000-2024, PeerView

54. PFS

gm zw os
so Median PFS: 6.9 months so Median OS: 23 months.
5 (95% CI, 5.6-8.8) € (95% Cl, 18.5-29.5)
3 © 5 ©
aw un 2 years
So 3 ©
3 3
£0 ¿sn
= 2years = 0
gx gx
E 5»
= 0 so
€ o € o
oT OO ROAM TDS ENENETEEEEEEETTT.
Time From Date of First Dose, mo Time From Date of First Dose, mo
No.atRink 114 85 60 41 37 90 29 16 12 6 4 2 1 0 NoRik 114108 101 83 75 67 59 59 46 42 2 13 6 3 2 2 0

+ As of September 12, 2022, the median follow-up was 19.2 months and median duration of treatment
was 7.5 months, with 48 of 114 (42%) patients alive

1. amido Pet a. ELCC 2023. Abstract 30. PeerView

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55. 22L Setting 1L Setting

Furmonertinib 3G EGFR TKI Phase 1b estilo Chemo Phase 3
+ chemo
Sunvozertinib 3G EGFR TKI Phase 1/2 Sunvozertinib 3G EGFR TKI Phase 1/2
Zipalertinib 3G EGFR TKI Phase 112 Furmonertinib 3G EGFR TKI Phase 1/3
PeerView

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56. Returning to Our Case and Panel Discussion

Patient History and Presentation

A 63-year-old woman presents with dyspnea

Workup > pleural effusion
Pleural fluid cytology positive for adenocarcinoma of lung
PET scan: multiple bilateral pulmonary nodules
ECOG PS 1
Liquid biopsy revealed an EGFR mutation; tissue NGS
from the resection sample showed the same findings
‘Ateraton sonar
FIVE. er =
EGER VITA CT7SraNPHY (exon 20 maeron) 14 =
SAS Ra o

STK F2SL
FGPRZG1038

PD-L1 TPS <1%

Comes to your clinic to discuss the biomarker testing results
and treatment options

Variant of uncertain signfeance
Variant of uncertain sigifieance

Let’s Discuss

Y How do we select among the
available treatment options, and
what are the considerations?

Copyright © 2000-2024, PeerView

57. Discussion =?
and Q&A