Amivantamab plus pembrolizumab in previously untreated recurrent/metastatic head and neck squamous cell cancer: Results from the phase 1b/2 OrigAMI-4 study

BACKGROUND: Prognosis is poor for patients with recurrent/metastatic (R/M) head and neck squamous cell cancer (HNSCC), warranting novel treatments. Epidermal growth factor receptor (EGFR) and MET are overexpressed in HNSCC and contribute to cancer progression and metastasis. Amivantamab, an EGFR-MET bispecific antibody, has demonstrated single-agent efficacy in R/M HNSCC after immune checkpoint inhibitor and platinum-based chemotherapy. Here, we report the efficacy and safety of first-line amivantamab plus pembrolizumab in participants with R/M HNSCC. METHODS: Cohort 2 of the phase 1b/2 OrigAMI-4 (NCT06385080) study enrolled participants with previously untreated R/M HNSCC and PD-L1 combined positive score ≥1. Patients with p16-positive oropharyngeal cancer and prior anti-EGFR or anti-PD-(L)1 therapy were excluded. Subcutaneous amivantamab and intravenous pembrolizumab were administered every 3 weeks. Primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included duration of response (DoR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Overall, 39 participants received ≥1 dose of subcutaneous amivantamab plus intravenous pembrolizumab in Cohort 2. At a median follow-up of 13.6 months, confirmed ORR was 59% (95% CI, 42-74), with 7 (18%) complete responses. Median DoR was not reached (NR). CBR was 74% (95% CI, 58-87). Shrinkage of target lesions occurred in 82% of participants. Median PFS was 7.7 months (95% CI, 5.0-NR); median OS was NR. The safety profile was consistent with prior reports, with no new safety signals identified. CONCLUSION: Subcutaneous amivantamab plus intravenous pembrolizumab demonstrated meaningful antitumor activity and may be a promising new option for previously untreated R/M HNSCC.

Authors

Institutions

Publication Details

Journal
Clinical Cancer Research
Published
2026-09-15
DOI
https://doi.org/10.1158/1078-0432.ccr-26-1372
Primary Topic
Head and Neck Cancer Studies
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

Amivantamab plus pembrolizumab in previously untreated recurrent/metastatic head and neck squamous cell cancer: Results from the phase 1b/2 OrigAMI-4 study

Ammar Sukari, Sung‐Bae Kim, Myung‐Ju Ahn, Remy B. Verheijen et al.
Clinical Cancer Research
Head and Neck Cancer Studies
article

Amivantamab plus pembrolizumab in previously untreated recurrent/metastatic head and neck squamous cell cancer: Results from the phase 1b/2 OrigAMI-4 study

Ammar Sukari, Sung‐Bae Kim, Myung‐Ju Ahn, Remy B. Verheijen, Jin‐Ching Lin, Ranee Mehra, Zara Vidales, Paul Swiecicki, Marc Oliva, Will Ince, Mahadi Baig, Kiichiro Toyoizumi, Hsiang‐Fong Kao, Emrullah Yilmaz, Kevin J. Harrington, Aarti Bhatia, Bhumsuk Keam, Ajay Mehta, Ewa Pawłowska, Hung‐Ming Wang, Joshua C. Curtin, Xuesong Lyu, Aastha Kapoor, Mark Wade, Sujay Shah, Malwinder S. Sandhu, Patricia Lorenzini
article en

Abstract

BACKGROUND: Prognosis is poor for patients with recurrent/metastatic (R/M) head and neck squamous cell cancer (HNSCC), warranting novel treatments. Epidermal growth factor receptor (EGFR) and MET are overexpressed in HNSCC and contribute to cancer progression and metastasis. Amivantamab, an EGFR-MET bispecific antibody, has demonstrated single-agent efficacy in R/M HNSCC after immune checkpoint inhibitor and platinum-based chemotherapy. Here, we report the efficacy and safety of first-line amivantamab plus pembrolizumab in participants with R/M HNSCC. METHODS: Cohort 2 of the phase 1b/2 OrigAMI-4 (NCT06385080) study enrolled participants with previously untreated R/M HNSCC and PD-L1 combined positive score ≥1. Patients with p16-positive oropharyngeal cancer and prior anti-EGFR or anti-PD-(L)1 therapy were excluded. Subcutaneous amivantamab and intravenous pembrolizumab were administered every 3 weeks. Primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included duration of response (DoR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Overall, 39 participants received ≥1 dose of subcutaneous amivantamab plus intravenous pembrolizumab in Cohort 2. At a median follow-up of 13.6 months, confirmed ORR was 59% (95% CI, 42-74), with 7 (18%) complete responses. Median DoR was not reached (NR). CBR was 74% (95% CI, 58-87). Shrinkage of target lesions occurred in 82% of participants. Median PFS was 7.7 months (95% CI, 5.0-NR); median OS was NR. The safety profile was consistent with prior reports, with no new safety signals identified. CONCLUSION: Subcutaneous amivantamab plus intravenous pembrolizumab demonstrated meaningful antitumor activity and may be a promising new option for previously untreated R/M HNSCC.

Clinical Cancer Research
University of Maryland, Baltimore (US), Johnson & Johnson (United States) (US), Institute of Cancer Research (GB), University of Michigan (US), Hospital Kuala Lumpur (MY), Cambridge University Hospitals NHS Foundation Trust (GB), Yale Cancer Center (US), Seoul National University Hospital (KR), University of Ulsan (KR), The Barbara Ann Karmanos Cancer Institute (US), Institute of Cancer Research (CA), Taoyuan Chang Gung Memorial Hospital (TW), Institut Català d'Oncologia (ES), Michigan Medicine (US), National Taiwan University Hospital (TW), Johnson & Johnson (United Kingdom) (GB), Royal Surrey NHS Foundation Trust (GB), CRUK Lung Cancer Centre of Excellence (GB), Johnson & Johnson (Netherlands) (NL), Changhua Christian Hospital (TW), Johnson & Johnson (Brazil) (BR), University of Baltimore (US), Gdańsk Medical University (PL), Sungkyunkwan University (KR)
Good health and well-being
Openalex Percentile: Top 8%
Head and Neck Cancer Studies
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.