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.