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

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.