3MO - Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutant advanced NSCLC after progression on osimertinib: A post-progression analysis of MARIPOSA-2

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.