Multinational phase 1b-2 study of amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy

Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). EGFR and MET are overexpressed in R/M HNSCC. Amivantamab, and EGFR-MET bispecific antibody, may be a rational treatment option. Cohort 1 of the multinational phase 1b-2 OrigAMI-4 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. Among 102 participants, blinded independent central review-assessed ORR was 42% (95% CI 32-52) with complete response in 15%. Median duration of response was not reached; 56% of responses lasted ≥ 6 months. At a median follow-up of 11.8 months (range 1.1-21.9), median progression-free survival was 6.8 months (95% CI 5.2-8.3) and median overall survival was 12.5 months (10.2-16.8). Adverse events were consistent with previous experience with no new safety signals. Treatment-related discontinuation was observed in 8% of participants. The authors conclude that amivantamab demonstrated greater antitumor activity in R/M HNSCC patients previously exposed to ICI and chemotherapy than what has been reported for paclitaxel or cetuximab.