The Phase 1/2 OrigAMI-4 trial (Cohort 2) tested a first-line combination of subcutaneous amivantamab (Rybrevant Faspro) and pembrolizumab (Keytruda) in patients with HPV-unrelated, PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The therapy showed a 56% overall response rate, 74% clinical benefit rate, and tumor shrinkage in 82% of patients, with median progression-free survival of 7.7 months. Common side effects were rash and paronychia, and the subcutaneous delivery reduced administration reactions compared to intravenous use.
Compared to Cohort 1 (previously treated patients using amivantamab alone), Cohort 2 demonstrated strong efficacy in treatment-naive patients, supporting progression to Phase 3.
Following these results, the Phase 3 OrigAMI-5 trial has started, testing subcutaneous amivantamab plus carboplatin and pembrolizumab against standard chemotherapy regimens. This study will include patients regardless of PD-L1 status, potentially expanding the therapy to more patients.