Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: Preliminary results from the phase 1b/2 OrigAMI-4 study
- PMID: 41275660
- DOI: 10.1016/j.oraloncology.2025.107791
Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: Preliminary results from the phase 1b/2 OrigAMI-4 study
Abstract
Overexpression of EGFR and MET occurs in a high proportion of recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Amivantamab, an EGFR-MET bispecific antibody with immune-cell directing activity, is approved in EGFR-mutated advanced non-small cell lung cancer and is being evaluated in phase 3 trials for other solid tumors. Cohort 1 of OrigAMI-4 (NCT06385080) enrolled adult participants with human papillomavirus-unrelated R/M HNSCC with disease progression on/after prior checkpoint inhibitor and platinum-based chemotherapy. Subcutaneous amivantamab was administered at 1600 mg (2240 mg for ≥ 80 kg body weight) on Cycle 1 Day 1 and 2400 mg (3360 mg for ≥ 80 kg body weight) thereafter. Primary end point was investigator-assessed objective response rate (ORR). As of July 1, 2025 (median follow-up, 3.5 months [range, 0-13.4]), 86 participants (median age, 63.5 years; 45 % Asian; 43 % White) received ≥ 1 dose of subcutaneous amivantamab. Subcutaneous amivantamab was well tolerated. Administration-related reactions were reported in 7 % (n = 6/86) of participants; no new safety signals were observed. In the efficacy population (n = 38; median follow-up, 8.3 months [range, 1.1-13.4]), confirmed ORR was 45 % (95 % CI, 29 %-62 %), median time to first response was 6.4 weeks (range, 5.7-18.3), and median duration of response was 7.2 months (95 % CI, 5.3-NE). The clinical benefit rate (responder or durable stable disease) was 76 % (95 % CI, 60 %-89 %). Median progression-free survival was 6.8 months (95 % CI, 4.2-9.0). Subcutaneous amivantamab as second-/third-line treatment among participants with R/M HNSCC demonstrated rapid and durable antitumor activity. The safety profile of subcutaneous amivantamab was consistent with previous studies.
Keywords: Amivantamab; Epidermal growth factor receptor (EGFR); Head and neck squamous cell carcinoma; Mesenchymal-epithelial transition (MET); Recurrent and metastatic.
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of competing interest Kevin J. Harrington received honoraria from AbbVie, ALX Oncology, AstraZeneca, BeOne Medicines, Bicara Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Exelixis, Flamingo Pharma (UK) Ltd, GSK, Johnson & Johnson, Merck Serono, Merus, MSD, Nanobiotix, PDS Biotech, PsiVac Ltd., Replimune, and Scenic Biotech; served in a consulting or advisory role for AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck Serono, MSD, Nanobiotix, and Replimune; participated in a speaker’s bureau for Bristol Myers Squibb, Merck Serono, and MSD; and received research funding from AstraZeneca, Boehringer Ingelheim, and Replimune.Ari J. Rosenberg served in a consulting or advisory role for Astellas Pharma Inc., Eisai, EMD Serono, Nanobiotix, Novartis, Regeneron, and Barinthus Biotherapeutics; participated in a speaker’s bureau for Coherus Oncology; received research funding from AbbVie, BeOne Medicines, Bristol Myers Squibb/Celgene, EMD Serono, Hookipa Pharma, and Purple Biotech; and received stock or stock options from Galectin Therapeutics and Privo Technologies, Inc.Muh-Hwa Yang received honoraria from Merck, MSD, Ono Pharmaceutical, and Pfizer; and served in a consulting or advisory role for MSD and Pfizer.Jessica L. Geiger served in a consulting or advisory role for Astellas Pharma Inc., Exelixis, Merck, and Regeneron; and received research funding from Alkermes, Genentech/Roche, Merck, Merck Serono, and Regeneron.Marc Oliva received grants or contracts for research from AbbVie, ALX Oncology, Ascendis Pharma, Ayala Pharmaceuticals, Inc., Bayer, BeOne Medicines, Boehringer Ingelheim, Debiopharm, Elixir, Gilead, GSK, ISA Therapeutics, Merck, MSD, Nykode, Pfizer, Roche, and Transgene; received consulting fees from BeOne Medicines, Merck Serono, MSD, and Transgene; received honoraria or payment from Bristol Myers Squibb, Merck Serono, and MSD; received travel, accommodations, and expenses from Boehringer Ingelheim, Bristol Myers Squibb, Merck Serono, and MSD; and participated in a data safety monitoring or advisory board for Merck Serono, MSD, Obatica, and Transgene.Myung-Ju Ahn received honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Merck, MSD, Takeda, and Yuhan; served in a consulting or advisory role for Amgen, AstraZeneca, BioNTech, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, Merck, MSD, and Takeda; holds patents/intellectual property or receive royalties from Yuhan.Sun Min Lim received honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, J Ints Bio, Eli Lilly, Merck, MSD, Oscotec, Takeda, Therapex, and Yuhan; received research funding from Johnson & Johnson, MSD, and Yuhan; and participated in a safety monitoring board for J Ints Bio, Pierre Fabre, Therapex, and Yuhan.William Ince received honoraria from AstraZeneca, Eisai, Ipsen, Merck Serono, and Recordati; served in a consulting or advisory role for Ipsen, Merck, and Recordati; received research funding from Merck; and received travel, accommodations, and expenses from Ipsen and Merck.Aarti Bhatia received honoraria from Clinical Care Options and Medscape; served in a consulting or advisory role for Adcendo, Daiichi Sankyo, and Coherus Oncology; and received research funding from Boehringer Ingelheim and Genentech.Siddharth Sheth received honoraria from Coherus Oncology, Eisai, and Inhibrx; has participated in a speaker’s bureau for Exelixis; has received research funding from AstraZeneca, Exelixis, Inovio Pharmaceuticals, Merck, and Regeneron; received travel, accommodations, and expenses from Merus.Bhumsuk Keam has no conflict of interest.Robert Metcalf served in a consulting or advisory role for Avacta Group.Joshua C. Curtin is an employee of Johnson & Johnson and may hold stock in Johnson & Johnson.Kiichiro Toyoizumi is an employee of Johnson & Johnson and may hold stock in Johnson & Johnson.Mark Wade is an employee of Johnson & Johnson and may hold stock in Johnson & Johnson.Emrullah Yilmaz is an employee of Johnson & Johnson and may hold stock in Johnson & Johnson.Priya Kim is an employee of Johnson & Johnson and may hold stock in Johnson & Johnson.Remy B. Verheijen is an employee of Johnson & Johnson and may hold stock in Johnson & Johnson.Sujay Shah is an employee of Johnson & Johnson and may hold stock in Johnson & Johnson.Mahadi Baig is an employee of Johnson & Johnson and may hold stock in Johnson & Johnson.Paul L. Swiecicki received consulting fees from Astellas Pharma Inc., CDR‑Life, Elevar, EMD Serono, GeoVax, Janssen, Prelude, Rapt Therapeutics, Regeneron, Remix, and Rgenta; received research funding from Ascentage Pharma and Summit Therapeutics; and holds patents/intellectual property or receive royalties related to ctDNA detection technology from Bio‑Rad.
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