513MO - Amivantamab plus FOLFOX or FOLFIRI in metastatic colorectal cancer: Results from OrigAMI-1, an open-label, phase Ib/II study

Background

Amivantamab (ami), an EGFR-MET bispecific antibody with immune cell-directing activity, has shown promising monotherapy activity in patients (pts) with relapsed/refractory metastatic colorectal cancer (mCRC; Oberstein JCO 2024;42[3_suppl]:135). Standard therapy for RAS/RAF wild-type (WT) mCRC is 5-FU–based doublet or triplet chemotherapy (FOLFOX or FOLFIRI) with or without biologics. With its unique mechanism of action, ami may offer improved efficacy and manageable safety when combined with FOLFOX or FOLFIRI.

Methods

OrigAMI-1 (NCT05379595) is assessing the safety and efficacy of ami (1050 mg [1400 mg if ≥80kg]) plus mFOLFOX6 or FOLFIRI in anti-EGFR-naïve RAS/RAF WT mCRC. Eligible pts were WT for KRAS, NRAS, BRAF, and EGFR ectodomain by ctDNA testing, without ERBB2/HER2 amplification. In the ami+chemotherapy cohorts, pts had received ≤1 prior line in the metastatic setting (no anti-EGFR treatment or chemotherapy [oxaliplatin- or irinotecan-based, respectively]). Response was assessed by the investigator per RECIST v1.1.

Results

As of 8 Apr 2024, 44 pts received ami+FOLFOX (n=21) or ami+FOLFIRI (n=23) at a median follow-up of 3.9 and 4.4 months (mo), respectively. Median age was 62 years and 71% were male. Most pts had left-sided mCRC and/or had received 1 prior line (see table). The best timepoint response rate was 63% (10/16) for ami+FOLFOX and 48% (11/23) for ami+FOLFIRI. Median duration of response (DoR) among confirmed responders was not estimable (NE) for ami+FOLFOX and 6.5 mo (95% CI, 5.6‒NE) for ami+FOLFIRI. See table for additional efficacy results. The most frequent treatment-emergent adverse events were rash and neutropenia. No new safety signals were observed. Biomarker analyses and updated results will be presented at the meeting. Table: 513MO

Summary

^aAs of data cutoff, 5 pts on ami+FOLFOX have not reached their first disease assessment. ^bDCR (disease control rate) is the percentage of pts achieving a confirmed/unconfirmed response or durable stable disease (duration ≥7 weeks). ^cAmong confirmed responders.

Conclusions

Ami+chemotherapy demonstrated encouraging, durable antitumor activity and a manageable safety profile in anti-EGFR-naïve RAS/RAF WT mCRC.

Clinical trial identification

NCT05379595.

Editorial acknowledgement

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

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Global Services, LLC.

Disclosure

F. Pietrantonio: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, MSD, Bayer, Astellas, Takeda, Ipsen, GSK, Johnson&Johnson, Rottapharm; Financial Interests, Personal, Invited Speaker: Amgen, Merck-Serono, BMS, Lilly, Servier, Bayer, Pierre-Fabre, AstraZeneca, Astellas, Daiichi Sankyo, Takeda; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Incyte, Agenus; Financial Interests, Institutional, Coordinating PI: Lilly, Amgen. G.F. Ho: Financial Interests, Personal, Financially compensated role, Honoraria: Merck & Co., Inc, F. Hoffmann-La Roche AG, Boehringer Ingelheim, AstraZeneca, Pfizer; Financial Interests, Personal, Financially compensated role, Hono: Novartis; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, Boeringer Ingelheim, Novartis, Merck Sharp & Dohme, Roche/Genentech; Financial Interests, Institutional, Research Funding: Merck Sharpe & Dohme, Tessa Therapeutics, AB Science, Pfizer, Regeneron Pharmaceuticals, AstraZeneca, ARCU, Astellas Pharma, F. Hoffman-La Roche AG, Janssen Research & Development, Boehringer Ingelheim, Amgen, Mirati Therapeutics, Novartis; Financial Interests, Personal, Other, Travel: Regeneron Pharmaceuticals. Y. Su: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Speaker’s Bureau: Merck, Johnson & Johnson, MSD, Bayer, Ono. P. Voon: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck Sharp & Dohme, Pfizer; Financial Interests, Personal, Advisory Board: Novartis, Ipsen, BeiGene; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Novartis, Boehringer Ingelheim, Janssen-Cilag, Johnson & Johnson, Viracta Therapeutics Inc, Roche, Merck KGaA, Merck Sharp & Dohme, BeiGene, Amgen, Revolutionary Medicine. D. Jonker: Financial Interests, Institutional, Research Funding: Janssen Research & Development. F. Longo Muñoz: Financial Interests, Personal, Other, Support: Amgen, Roche, Lilly, BMS, MSD, Servier, Merck. J.R. Hecht: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas, BMS, Taiho, BeiGene, IGM, Novartis, Galvanize, Exelixis, Deciphera; Financial Interests, Personal, Speaker’s Bureau: Scripps, American Gastroenterological Association, MJH Life Sciences, Research to Practive; Financial Interests, Personal, Stocks or ownership: Triumvira, Actym, MBQ Pharma. S. Chandana: Financial Interests, Institutional, Research Funding: Abbvie, Adcentrx Therapeutics, Amgen, AstraZeneca, Cardiff Oncology, Deciphera, Elevation Oncology, Exact Sciences, Genetech/Roche, Ideaya Biosciences, IGM Biosciences, Incyte, Ipsen, Janssen, Merck, Mirati Therapeutics, Novocure, Qualigen Therapeutics, Zymeworks; Financial Interests, Personal, Speaker’s Bureau: Natera. D. Arnold: Financial Interests, Personal, Invited Speaker: AstraZeneca, Sanofi (Genzyme), Boston Scientific, Amgen, Merck (Serono), Servier, Ipsen, Boehringer Ingelheim, Eisai, GSK, Viatris, Amgen, Sirtex, PeerMD (China); Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Pierre Fabre Pharma, Boston Scientific, AstraZeneca, Gilead, Janssen Cilag; Financial Interests, Personal, Advisory Board, Advisory Board participations and Invited Speaker roles: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board, Advisory Board participation and Invited Speaker role: Terumo, Seagen, Amgen, Takeda; Financial Interests, Personal, Invited Speaker, CME Provider: PRMA Consulting, Tactics MD LLC, WebMD Health Corp, From Research to Practice, Aptitude Health, Art Tempi Media, Imedex, Streamitup Germany, Clinical Care Options (CCO), MCI, IOMEDICO (Germany); Financial Interests, Personal, Advisory Board, Consulting Agency: CRA International; Financial Interests, Personal, Advisory Board, CME Provider, App Producer: Onkowissen; Financial Interests, Personal, Other, Roles as Assoc. Editor for ESMO Open and Ann Oncol: Elsevier; Financial Interests, Personal, Other, Role as Associate Editor Clin Colorectal Cancer: Elsevier; Financial Interests, Institutional, Other, DSMB Chair: Sanofi (Genzyme); Financial Interests, Institutional, Coordinating PI: OncoLytics; Financial Interests, Institutional, Funding, Educational Grant: AbbVie; Non-Financial Interests, Project Lead, non-compensated Scientific Advisory Board member: OncoLytics; Non-Financial Interests, Advisory Role, non-compensated Scientific Advisory Board member: Phanes Therapeutics Inc.; Non-Financial Interests, Leadership Role, GI Group Steering Committee: EORTC; Non-Financial Interests, Leadership Role, Steering Committee Member: AIO (German Cancer Society); Non-Financial Interests, Member: ASCO, ESO, DGHO. R. Bhattacharya, J.C. Curtin, S. Maul, R. Iwasawa, S. Chowdhury,. W. Schnepp, M. Baig: Financial Interests, Full or part-time Employment: Janssen Research & Development. All other authors have declared no conflicts of interest.