398TiP - MARIPOSA-2: Randomized phase III study of amivantamab + lazertinib + chemotherapy vs chemotherapy alone in EGFR-mutant NSCLC after osimertinib failure

Background

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) effectively treat patients with non-small cell lung cancer (NSCLC) with EGFR-sensitizing mutations; however, almost all will eventually relapse due to new mutations on or after osimertinib the 3^rd generation TKI. The current standard of care is platinum doublet chemotherapy after progression on osimertinib, but with limited benefit. Amivantamab, an EGFR and MET bispecific humanized antibody, has shown clinical activity against tumors with primary activating EGFR mutations, EGFR resistance mutations, or MET pathway activation. Lazertinib is an oral, brain-penetrant, 3^rd generation EGFR TKI. Amivantamab and lazertinib in combination has demonstrated clinically significant activity in post-osimertinib disease. Amivantamab and lazertinib in combination with platinum-based chemotherapy after osimertinib failure would provide improved clinical benefits compared to chemotherapy alone.

Trial design

MARIPOSA-2, a randomized, open-label, Phase 3 study, will evaluate the efficacy and safety of lazertinib, amivantamab, carboplatin, and pemetrexed (“LACP”; Arm A) vs carboplatin and pemetrexed (“CP”; Arm B) in participants with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC following progression on or after osimertinib. A third treatment group will receive amivantamab, carboplatin, and pemetrexed (“ACP”; Arm C) to assess the contribution of lazertinib in the LACP. There will be 500 eligible participants randomly assigned 2:2:1 (Arms A:B:C) and stratified by osimertinib line of therapy (1^st vs 2^nd-line), brain metastases, and Asian race. Efficacy will be assessed by blinded independent central review (RECIST v1.1); the primary endpoint will be progression-free survival; key secondary endpoints include objective response rate, overall survival, safety, and health-related quality of life.

Clinical trial identification

NCT04988295.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

R. Garcia Campelo: Financial Interests, Personal, Other, Honoraria: Pfizer, Novartis, Roche, Lilly, AstraZeneca, Takeda, MSD; Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Roche, Lilly, AstraZeneca, Takeda, MSD; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, Roche, Lilly, AstraZeneca, Takeda, MSD. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca. 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. K. Reckamp: Financial Interests, Personal, Other, consultant: Amgen, AstraZeneca, Blueprint, Daiichi Sankyo, Genentech, GlaxoSmithKline, Janssen, Lilly, Mirati, Takeda; Financial Interests, Personal, Advisory Board: EMD Soreno, Merck KGA; Financial Interests, Personal, Invited Speaker: Seattle Genetics,; Financial Interests, Institutional, Invited Speaker: Genentech, Blueprint, Calithera, Daiichi Sankyo, Elevation Oncology, Janssen. T. Takahashi: Financial Interests, Personal, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Boehringer Ingelheim Japan, Inc., Takeda Pharmaceutical Co Ltd., Yakult Honsha Co. Ltd; Financial Interests, Institutional, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Amgen Inc., Merck Biopharma Co., Ltd. S. Li, D. Millington, P. Barala: Financial Interests, Personal, Full or part-time Employment: Janssen R&D. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen Research and Development; Financial Interests, Personal, Stocks/Shares: Janssen Research and Development. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment, I am an employee of Janssen Oncology R&D and therefore received salary and long-term compensation in the form of company stocks: Janssen Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah BIO; Financial Interests, Personal, Invited Speaker: Gencurix Inc, Interpark Bio Convergence Corp.; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Institutional, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp.; Other, Personal, Other, Founder: DAAN Biotherapeutics. All other authors have declared no conflicts of interest.