Background

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. In MARIPOSA-2 (NCT04988295), ami plus carboplatin-pemetrexed (ami-chemo) significantly prolonged progression-free survival (PFS) vs chemo in patients (pts) with EGFR-mutant advanced NSCLC after progression on osimertinib (Passaro Ann Oncol 2023). Post-progression outcomes from MARIPOSA-2 were assessed.

Methods

657 pts were randomized. These analyses focus on the 131 pts randomized to ami-chemo (safety: n=130) and 263 to chemo (safety: n=243). A third arm (ami-lazertinib-chemo) was modified and will be reported in the future. Post-progression endpoints were time to treatment discontinuation (TTD), time to subsequent therapy (TTST), and PFS after first subsequent therapy (PFS2).

Results

At a median follow-up of 8.7 months (mo), 55/130 (42%) pts in the ami-chemo arm and 173/243 (71%) in the chemo arm had progressive disease (PD). Among those with PD, 19/55 (35%) in the ami-chemo arm and 28/173 (16%) in the chemo arm were treated beyond progression for >4 weeks with a median (95% CI) post-progression treatment duration of 18.3 (9.0–NE) and 9.0 (6.0–16.4) weeks, respectively. Compared to chemo, ami-chemo significantly prolonged TTD (median, 11.0 vs 4.5 mo for chemo; HR, 0.37 [95% CI, 0.28–0.50]; P<0.0001), TTST (median, 12.1 vs 6.6 mo for chemo; HR, 0.42 [95% CI, 0.30–0.59]; P<0.0001), and PFS2 (median, 13.9 vs 11.3 mo for chemo; HR, 0.60 [95% CI, 0.40–0.92]; P=0.017). Among pts with PD, including pts treated beyond PD, 75% (41/55) in the ami-chemo arm discontinued treatment after progression vs 93% (161/173) for chemo. 63% of pts with PD initiated subsequent systemic therapy in both arms. Most common subsequent therapies were osimertinib (ami-chemo:10%; chemo: 9%) and docetaxel (ami-chemo: 7%; chemo: 9%).

Conclusions

Ami-chemo significantly prolonged TTD, TTST, and PFS2 vs chemo. Ami-chemo represents the new standard of care for pts with EGFR-mutant advanced NSCLC after PD on osimertinib.

Clinical trial identification

NCT04988295.

Editorial acknowledgement

Medical writing assistance was provided by Lumanity Communications Inc and funded by Janssen Global Services LLC.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

R.D. Gentzler: Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Pfizer, Amgen, Chugai, Merck, AstraZeneca, Janssen, Daiichi Sankyo, AllianceFoundation, Takeda, ECOG/ACRIN, Jounce Therapeutics, Bristol Myers Squibb, NCI, Big Ten Research Consortium, Hoosier Cancer Research Network, SWOG, Helsinn; Financial Interests, Personal, Speaker’s Bureau: Clinical Care Options, OncLive, Targeted Oncology, Society for Immotherapy of Cancer (SITC); Financial Interests, Personal, Other, Travel: International Association for the Study of Lung Cancer (IASLC); Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Takeda, Gilead, Janssen, Mirati, Sanofi, Oncocyte, Jazz Pharmaceuticals, BluePrint Medicines; Financial Interests, Personal, Leadership Role: Hoosier Cancer Research Network, Thoracic Clinical Trial Working Group, ASCO Scientific Review Committee, Journal of Clinical Oncology, ASCO Meeting Abstracts; Financial Interests, Personal, Licensing Fees: NCI Investigational Drug Steering Committee. A. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Invited Speaker: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med. B. Melosky: Financial Interests, Personal, Speaker’s Bureau: Pfizer, BMS, Merck, Roche, Janssen, AstraZeneca, Takeda, Jazz, Boehringer Ingelheim, EMD Serono, Novartis, Sanofi; Financial Interests, Personal, Other, Travel: Pfizer, Sanofi, Janssen. S. Owen: Financial Interests, Personal, Other, Consulting Fees: Janssen, Bristol Myers Squibb, Novocure, Roche. T. Burns: Financial Interests, Personal, Other, Support: Janssen Global Services, LLC; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, Consulting Fees: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Amgen Mexico; Financial Interests, Personal, Advisory Board: Blueprint Medicines, Amgen, Jazz Pharmaceuticals, Mirati Therapeuticals, EMD Serono, Takeda, Janssen, AstraZeneca, Advarra, Inc. E. Massarelli: Financial Interests, Personal, Advisory Board: Merck & Co., Janssen Pharmaceuticals, Eli Lilly and Company, Sanofi-Aventis, Bristol Myers Squibb Company, Genentech, Inc, Daiichi Sankyo Co., AbbVie, Inc., Mirati Therapeutics, Iovance Biotherapeutics; Financial Interests, Personal, Other, Speaker Bureau: AstraZeneca, Merck & Co., Eli Lilly and Company, Takeda Pharmaceuticals; Financial Interests, Institutional, Other, Investigator: Merck & Co., AstraZeneca Pharmaceuticals, Janssen Pharmaceutical, Daiichi Sankyo Co.; Financial Interests, Institutional, Invited Speaker: GSK, Boston Biomedical, Genentech, Inc., Pfizer Inc., Bristol Myers Squibb, Kite Pharma, AbbVie, Inc., ARIAD Phamaceuticals, Eli Lilly and Company, Takeda Pharmaceuticals. M. Nagasaka: Financial Interests, Personal, Advisory Board: AstraZeneca, Caris Life Sciences, Daiichi Sankyo, Novartis, EMD Serono, Janssen, Pfizer, Genentech, Mirati, Regeneron, Silverback; Financial Interests, Personal, Invited Speaker: Takeda, Blueprint; Financial Interests, Personal, Expert Testimony: Lilly; Financial Interests, Personal, Other, Travel: AnHeart. B. Fang: Financial Interests, Institutional, Research Grant: Janssen, Amgen, Genentech, Exelixis, Epizyme, AstraZeneca, Daiichi Sankyo, Jazz, Ispen, Gilead, Lilly, Gritstome Bio, Novocure, PharmaEssentia, Allogene, Alkermes. R.E. Sanborn: Financial Interests, Personal, Advisory Board: AstraZeneca, EMD Serono, Daiichi Sankyo, Lilly Oncology, Janssen Oncology, Macrogenics, Sanofi Aventis, Regeneron, Mirati Therapeutics, GSK, G1 Therapeutics; Financial Interests, Personal, Invited Speaker: Illumina, GSK, Janssen Oncology; Financial Interests, Institutional, Funding, Funding for investigator-sponsored trial: Merck, AstraZeneca; Financial Interests, Institutional, Other, Institutional research support: BMS; Financial Interests, Institutional, Funding, Clinical trial funding: Jounce. O.G. Arrieta Rodriguez: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche; Financial Interests, Personal, Other, Consulting: AstraZeneca, Bristol Myers Squibb, Lilly, Merck, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Merck, Roche; Financial Interests, Personal, Other, Travel: Lilly. C. Card: Financial Interests, Personal, Other, Support: Janssen. F. Cappuzzo: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, GALECTO and MSD; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, andMSD. K. Xia, P. Chu, S. Shah, B. Diorio, A. Garvin, P. Mahadevia: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. K. Reckamp: Financial Interests, Personal, Other, consultant: Amgen, AstraZeneca, Blueprint, Daiichi Sankyo, Genentech, GSK, Janssen, Lilly, Mirati, Takeda; Financial Interests, Personal, Advisory Board: EMD Serono, Merck KGA; Financial Interests, Personal, Invited Speaker: Seattle Genetics,; Financial Interests, Institutional, Invited Speaker: Genentech, Blueprint, Calithera, Daiichi Sankyo, Elevation Oncology, Janssen.

Background

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. Lazertinib (laz) is a CNS-penetrant 3rd-generation EGFR TKI. As first-line treatment, ami+laz demonstrated superior progression-free survival (PFS) vs osimertinib in patients (pts) with EGFR-mutant advanced non-small cell lung cancer (NSCLC; Cho Ann Oncol 2023). Protocol guidance in the MARIPOSA study (NCT04487080) recommended an ami dose interruption in the case of related grade ≥2 toxicity. For pts treated with first-line ami+laz, the majority of key adverse events occurred in the first 4 months (mo; Spira JTO 2023). We studied the efficacy and safety in ami+laz pts that had ami dose interruptions in the first 4 months.

Methods

This analysis included all pts who were randomized to the ami+laz arm in MARIPOSA (efficacy set: n=429, safety set: n=421). Study protocol dictated ami to be dose modified before laz. Dose interruptions were defined as any interruptions of ami due to any cause.

Results

Among the 429 pts who were randomized to the ami+laz arm, 421 received at least one dose. At a median follow-up of 22.0 months, 49% (206/421) had ami dose interruptions in the first 4 months of treatment. Among pts who required ami dose interruptions in the first 4 months, the median PFS was 23.9 mo (95% CI, 18.5–NE). Median PFS, objective response rate (ORR), and median duration of response (DoR) for pts with and without dose interruptions of ami in the first 4 months were similar to all pts randomized to the ami+laz arm, as shown in the table. Updated analyses, including the impact of dose interruptions on treatment tolerability, will be presented at the time of the meeting. Table: 5MO

Efficacy endpoints among patients with and without ami dose interruptions within the first 4 months of receiving Ami+Laz

Conclusions

Among pts receiving ami+laz, early dose modifications of ami per protocol guidance did not adversely impact the efficacy of the combination. Ami+laz is a new first-line standard of care for pts with EGFR-mutant advanced NSCLC.

Clinical trial identification

NCT04487080.

Editorial acknowledgement

Katharine Fang, PhD (Janssen Global Services), with support from Lumanity Communications Inc.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

M.R. García Campelo: Financial Interests, Personal, Other, Consulting Fees: AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; Janssen Oncology; MSD Oncology; Novartis; Pfizer; Roche/Genentech; Takeda; Financial Interests, Personal, Speaker’s Bureau: Amgen; AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; Janssen Oncology; Lilly; MSD Oncology; Novartis; Pfizer; Roche; Sanofi/Aventis; Takeda; Financial Interests, Personal, Other, Travel: MSD Oncology; Pfizer; Roche/Genentech. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, RandBio, Hanmi, GC Cell, Gilead, Ridgeline Discovery GmbH; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen, AstraZeneca, Regeneron, Seagen, Samsung Bioepis; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, Gradiant Bioconvergence, Therapex, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, JINTSbio, Hanmi, Daewoong Pharmaceutical Co., Ltd., Vertical Bio AG, Korea Institute of Oriental Medicine, National Research Foundation of Korea, KHIDI; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Personal, Other, Family member is an employee: AstraZeneca. H. Yoshioka: Financial Interests, Personal, Invited Speaker, Lecture fee: Eli Lilly Japan K.K., Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Advisor: Delta-Fly Pharma; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Janssen Pharmaceutical, MSD, Novartis Pharma, Delta-Fly Pharma, Boehringer Ingelheim. J. Lee: Financial Interests, Personal, Other, Consulting Fees: Yuhan Corporation. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck, Pfizer, Lilly, BMS/Ono, Takeda, Janssen, IMBdx; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck, Lilly, Amgen; Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Lunit. M.A.N. Sendur: Financial Interests, Personal, Advisory Board: BMS, Pfizer, Takeda, Roche, Astellas; Financial Interests, Personal, Invited Speaker: Astellas, Pfizer, BMS, MSD, Roche. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Beigene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi Aventis, Springer Healthcare Ltd, 4D Pharma; Financial Interests, Institutional, Expert Testimony: AbbVie, Da voltera, Eli Lilly, Ellipse pharma Ltd, F-Star, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Socar research, Taiho oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD, AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi Sankyo, GSK, Janssen, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Turning Point Therapeutics, Genmab, Taiho, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Funding: Cristal Therapeutics. A. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Invited Speaker: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. J. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Guardant Health, BeiGene, Takeda, Lilly, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx; Financial Interests, Personal, Expert Testimony: Merck Serono, Roche; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology; Financial Interests, Personal, Other, Journal Deputy Editor, Lung Cancer: Elsevier; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Invited Speaker: Ariad, AstraZeneca, Roche, Boehringer Ingelheim, Celgene, Daiichi Sankyo, GSK, Takeda, Trizel, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Personal, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Personal, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Personal, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Personal, Advisory Role, Mesothelioma Task-force Member, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Personal, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Personal, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Personal, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board Member, Unpaid: Lung Cancer Europe. P. Mahadevia, S. Sethi, J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. All other authors have declared no conflicts of interest.

Background

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity approved as intravenous (IV) formulation. Subcutaneous (SC) ami substantially reduces severity/incidence of infusion-related reactions (IRRs; 16% SC vs 67% IV) and administration time (≤7 minutes SC vs 2–4 hours IV; Minchom ASCO 2023). We identified a Q4W dose for ami SC with comparable activity/safety to the IV dose thus further improving patient (pt)/provider experience.

Methods

PALOMA (NCT0406381) evaluated administration feasibility, safety, and pharmacokinetics of ami SC in pts with advanced solid tumors who may benefit from EGFR/MET-directed therapy. Ami SC was dosed weekly for the first 4 weeks (1600 mg [≥80 kg: 2240 mg]), Q4W thereafter (3200 mg [≥80 kg: 4320 mg]), and was administered by manual push injection in the abdomen.

Results

There are 127 pts enrolled, with 19 pts (median age: 62 years) having received ami SC Q4W as of 16 Nov 2023. Most pts were Asian (68%) and female (53%); 17 (89%) pts had non-small cell lung cancer. Four pts (21%) experienced IRRs, all grade 1–2 after first dose only. IRR-associated symptoms were pyrexia (2 pts), chills, pruritus, urticaria, and myalgia (1 pt each). Most common adverse events (AEs) were rash (79%; primarily grade 1-2, 2 cases grade 3), paronychia (58%), myalgia (47%), fatigue, nausea, stomatitis (32% each), peripheral edema and pyrexia (26% each). Eight pts (42%) experienced grade ≥3 AEs, with 3 (16%) treatment-related (rash 2 pts, hypokalemia 1 pt). Two pts discontinued ami SC due to AEs unrelated to treatment. The geometric mean values for Cycle 2 C_trough and AUC_0-672h for the tested Q4W SC dose were 325 μg/mL and 286612 μg•h/mL, respectively. The SC Q4W dose was refined to 3520 mg (≥80 kg: 4640 mg) to better match the steady state C_trough of the approved IV Q2W dose. Simulated geometric mean ratios for the refined Q4W dose vs reference IV dose at steady state were 0.92 (90% CI, 0.76–1.11) for C_trough and 1.27 (90% CI, 1.18–1.36) for AUC_0-672h.

Conclusions

Ami SC Q4W had lower rates of IRRs and was better tolerated vs ami IV. The ami SC Q4W dose of 3520 mg (≥80 kg: 4640 mg) achieved comparable exposure to the approved IV dose and is being further evaluated in the phase II, PALOMA-2 (NCT05498428) study.

Clinical trial identification

NCT0406381.

Editorial acknowledgement

Medical writing assistance was provided Lumanity Communications Inc and funded by Janssen Global Services LLC.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Lilly, MSD, Pfizer, Roche, Takeda, Janssen. A.R. Minchom: Financial Interests, Personal, Other, Expenses: Amgen pharmaceuticals, LOXO oncology; Financial Interests, Personal, Invited Speaker: Bayer Pharmaceuticals, Chugai Pharmaceuticls, GSK, Janssen Pharmaceuticals, Merck pharmaceuticals; Financial Interests, Personal, Advisory Board: Faron pharmaceuticals, Janssen Pharmaceuticals, Merck pharmaceuticals, Takeda, Genmab; Financial Interests, Personal, Expert Testimony: GSK; Financial Interests, Institutional, Other, Research funding: MSD, Merck Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Novartis Oncology. K.H.H. Lee: Financial Interests, Personal, Advisory Board: BMS, MSD, Eli Lilly, Yuhan, Pfizer, AstraZeneca; Financial Interests, Personal, Funding: Merck. M.G. Krebs: Financial Interests, Personal, Advisory Board: Bayer, Roche, Janssen, Guardant Health; Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Blueprint, Astex, Bayer, BerGenBio, Carrick, Immutep, Janssen, Novartis, Nurix, Nuvalent, Pyramid Biosciences, Roche, Seattle Genetics, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Novartis; Other, Personal, Other, Travel expenses for congress: Immutep, Janssen; Other, Personal, Other, Travel expenses: Roche. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, RandBio, Hanmi, GC Cell, Gilead, Ridgeline Discovery GmbH; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen, AstraZeneca, Regeneron, Seagen, Samsung Bioepis; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, Gradiant Bioconvergence, Therapex, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, JINTSbio, Hanmi, Daewoong Pharmaceutical Co., Ltd., Vertical Bio AG, Korea Institute of Oriental Medicine, National Research Foundation of Korea, KHIDI; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. M.L. Johnson: Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Ideaya Biosciences, Immunocore, iTeos, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, Turning Point Therapeutics, VBL Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics. J. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics. B. Sanusi, A. Alhadab, N. Haddish-Berhane, D. Zemlickis, A. Mitselos, C. Collins, M. Baig, J.M. Bauml, R.E. Knoblauch, P. Hellemans: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. R.E. Sanborn: Financial Interests, Personal, Advisory Board: AstraZeneca, EMD Serono, Daiichi Sankyo, Lilly Oncology, Janssen Oncology, Macrogenics, Sanofi Aventis, Regeneron, Mirati Therapeutics, GSK, G1 Therapeutics; Financial Interests, Personal, Invited Speaker: Illumina, GSK, Janssen Oncology; Financial Interests, Institutional, Funding, Funding for investigator-sponsored trial: Merck, AstraZeneca; Financial Interests, Institutional, Other, Institutional research support: BMS; Financial Interests, Institutional, Funding, Clinical trial funding: Jounce. All other authors have declared no conflicts of interest.

Background

Atezo SC is approved for use in all atezo IV indications in the EU and UK. Results from IMscin001 (NCT03735121) showed that the pharmacokinetics, efficacy and safety of atezo SC and IV were consistent. IMscin002 (NCT05171777) is a phase II, randomized, multicentre, cross over trial investigating pt- and HCP-reported preference for atezo SC vs IV for the treatment of pts with NSCLC.

Methods

Pts with PD-L1+ resected NSCLC (Stage II, IIIA, or selected IIIB; AJCC 8th ed) who had prior chemotherapy and no evidence of recurrence, and untreated pts with PD-L1 high Stage IV NSCLC were screened. Eligible pts ≥18 years old and EGFR/ALK wild-type were randomized 1:1 to receive atezo SC (1875 mg) or IV (1200 mg) Q3W. After Cycle 3, pts switched over to the alternative route of administration; after Cycle 6, pts stated their preference and selected treatment for the continuation period. Pts with resected NSCLC continued treatment for ≤16 cycles. Pts with advanced NSCLC continued treatment until investigator-determined loss of clinical benefit. The primary endpoint was pt preference for atezo SC vs IV at Cycle 6. Key secondary endpoints: safety and pt-reported outcomes assessed by questionnaire.

Results

At data cutoff (9 Nov 2023), 179 pts were randomized; 117 pts had Stage IV NSCLC and 62 pts had resected NSCLC. The completion rate for the pt preference questionnaire was 97.6% (n=123/126): most pts (70.7%) preferred atezo SC (n=87, 95% CI 61.9–78.6); 21.1% preferred IV (n=26); 8.1% had no preference (n=10). Pts’ main reasons for preferring atezo SC were that it reduces time in the clinic (64.4%, n=56/87) and is a more comfortable route of administration (46.0%, n=40/87). After Cycle 6, most pts (79.4%) chose atezo SC for the continuation period. Overall, 85.8% of pts were very satisfied/satisfied with atezo SC vs 75.2% of pts with IV. No new safety findings were identified, and no safety concerns related to switching between treatments were reported.

Conclusions

IMscin002 met its primary endpoint: pts preferred atezo SC vs IV. The overall safety profile was consistent with prior reports. These results support previous findings that pts prefer SC to IV formulations.

Clinical trial identification

NCT05171777.

Editorial acknowledgement

This study is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of the authors, was provided by Claire White, PhD of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

F. Cappuzzo: Non-Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Pharmamar, Novocure, Mirati, Galecto, OSE, ILLUMINA, Thermofisher, MSD; Non-Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Pharmamar, Novocure, Mirati, Galecto, OSE, Illumina, Thermofisher, MSD; Non-Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Pharmamar, Novocure, Mirati, Galecto, OSE, Illumina, Thermofisher, MSD. Z. Zvirbule: Financial Interests, Institutional, Advisory Board, Cervical cancer: MSD; Financial Interests, Personal, Invited Speaker, Lung cancer: Roche; Financial Interests, Personal, Advisory Board, OVARIAN CANCER: GSK. E.P. Korbenfeld: Financial Interests, Personal, Shares: Centro Oncológico Korben; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Honoraria: AstraZeneca. M.D. Isla Casado: Financial Interests, Personal, Speaker's Bureau: Pfizer, AstraZeneca, MSD, Roche, Sanofi, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis; Financial Interests, Personal, Advisory Role: Sanofi, AstraZeneca, MSD, Bristol-Myers Squibb, Janssen, GSK, Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, MSD, Pfizer, Roche/Genentech; Financial Interests, Personal, Other, Honoria: Roche/Genentech, MSD Oncology, AstraZeneca, Sanofi, Bristol-Myers Squibb, Amgen, Pfizer, Merck, Novartis. A.Y. Castro Sanchez: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Royalties: F. Hoffmann-La Roche Ltd. A. Bustillos: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Royalties: F. Hoffmann-La Roche Ltd. L.X. Liu: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc. F. Young: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. M. Majem: Non-Financial Interests, Personal, Invited Speaker: Roche, Merck Sharp & Dohme, Pfizer, AstraZeneca, Helsinn Therapeutics; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Pfizer, Boehringer Ingelheim, Novartis, Helsinn Therapeutics, Takeda, Sanofi, Janssen Oncology, Pierre Fabre, Bristol-Myers Squibb, AstraZeneca, Roche; Financial Interests, Personal, Other, Travel, Accommodations and Expenses; Research Funding: AstraZeneca, Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD Oncology; Financial Interests, Personal, Other, Research Funding: Bristol-Myers Squibb.

All other authors have declared no conflicts of interest.