Amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study

Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC). EGFR and MET are overexpressed in R/M HNSCC. Amivantamab, an EGFR-MET bispecific antibody, may be a rational treatment. Cohort 1 of OrigAMI-4 (NCT06385080) evaluated subcutaneous amivantamab administered every three weeks in participants with R/M HNSCC after PD-(L)1 inhibitor and platinum-based chemotherapy. Prior anti-EGFR was exclusionary. The primary endpoint was RECIST v1.1 ORR. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. In 102 participants, blinded independent central review-assessed ORR was 42% (95% CI, 32-52); the complete response rate was 15%. Median DoR was not reached (NR; 95% CI, 6.9-NR); 56% of responses lasted ≥6 months. Investigator-assessed ORR was 47% (95% CI, 37-57). At a median follow-up of 11.8 months (range, 1.1-21.9), median PFS and OS were 6.8 months (95% CI, 5.2-8.3) and 12.5 months (95% CI, 10.2-16.8), respectively. Adverse events were consistent with previous experience with no new safety signals. Treatment-related discontinuations were low (8%). Amivantamab demonstrated greater antitumor activity in participants previously exposed to ICI and chemotherapy than what has been reported for paclitaxel or cetuximab.

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Journal
Journal of Clinical Oncology
Published
2026-05-31
DOI
https://doi.org/10.1200/jco-26-01042
Primary Topic
Head and Neck Cancer Studies
Type
article
Field-Weighted Citation Impact
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article

Amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study

Brooke Diorio, Remy B. Verheijen, Mahadi Baig, Kiichiro Toyoizumi et al.
Journal of Clinical Oncology
Head and Neck Cancer Studies
article

Amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study

Brooke Diorio, Remy B. Verheijen, Mahadi Baig, Kiichiro Toyoizumi, Emrullah Yilmaz, D Hahn, Priya Kim, Hideki Tanaka, John Xie, Irene Braña, Joshua C. Curtin, Xuesong Lyu, Siddharth Sheth, Sujay Shah, K J Harrington, Ammar Sukari, Jessica L Geiger, Ye Guo, Douglas Adkins, Muh-Hwa Yang, William Ince, Marc Oliva, Ari J Rosenberg, Shigenori Kadowaki, Aastha Kapoor, Benoit Calderon, Mark Wade, Myung-Ju Ahn, Shau-Hsuan Li, Bhumsuk Keam, Robert Metcalf, Barbara Burtness, Paul L Swiecicki, Sun Min Lim
article en

Abstract

Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC). EGFR and MET are overexpressed in R/M HNSCC. Amivantamab, an EGFR-MET bispecific antibody, may be a rational treatment. Cohort 1 of OrigAMI-4 (NCT06385080) evaluated subcutaneous amivantamab administered every three weeks in participants with R/M HNSCC after PD-(L)1 inhibitor and platinum-based chemotherapy. Prior anti-EGFR was exclusionary. The primary endpoint was RECIST v1.1 ORR. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. In 102 participants, blinded independent central review-assessed ORR was 42% (95% CI, 32-52); the complete response rate was 15%. Median DoR was not reached (NR; 95% CI, 6.9-NR); 56% of responses lasted ≥6 months. Investigator-assessed ORR was 47% (95% CI, 37-57). At a median follow-up of 11.8 months (range, 1.1-21.9), median PFS and OS were 6.8 months (95% CI, 5.2-8.3) and 12.5 months (95% CI, 10.2-16.8), respectively. Adverse events were consistent with previous experience with no new safety signals. Treatment-related discontinuations were low (8%). Amivantamab demonstrated greater antitumor activity in participants previously exposed to ICI and chemotherapy than what has been reported for paclitaxel or cetuximab.

Journal of Clinical Oncology
University of North Carolina at Chapel Hill (US), Hebron University (PS), Cleveland Clinic (US), Johnson & Johnson (United States) (US), Tokyo Medical University (JP), Chang Gung University (TW), University of Michigan (US), University Health System (US), Yale Cancer Center (US), Seoul National University Hospital (KR), Taipei Veterans General Hospital (TW), University of Chicago (US), The Barbara Ann Karmanos Cancer Institute (US), Kaohsiung Chang Gung Memorial Hospital (TW), Vall d'Hebron Institut de Recerca (ES), Jewish Hospital (US), Institut Català d'Oncologia (ES), Johnson Controls (Japan) (JP), Royal Marsden Hospital (GB), Vall d'Hebron Hospital Universitari (ES), Shanghai East Hospital (CN), Johnson Electric (China) (CN), Aichi Cancer Center (JP), The Christie NHS Foundation Trust (GB), Duran i Reynals Hospital (ES), Hanyang University Medical Center (KR), Addenbrooke's Hospital (GB), Institut Sainte Catherine (FR), Johnson & Johnson (Netherlands) (NL), Johnson & Johnson (Brazil) (BR), Yonsei University Health System (KR), Klinikum Stuttgart (DE)
Good health and well-being
Openalex Percentile: Top 5%
Head and Neck Cancer Studies
DOIOpen Access PDFOpenAlex
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