Subcutaneous Amivantamab Cancer Trial Shows Promising Results in Head and Neck Squamous Cell Carcinoma

The Phase 1b/2 OrigAMI-4 study demonstrated that subcutaneous amivantamab and hyaluronidase-lpuj produced a confirmed overall response rate of 42 percent in patients with recurrent or metastatic head and neck squamous cell carcinoma previously treated with immunotherapy and platinum-based chemotherapy. More than one-third of responders achieved complete responses, and the median duration of response was not reached at a median follow-up of 11.8 months.

High Response Rates and Unreached Duration Highlight Therapeutic Potential

These results were presented at the 2026 American Society of Clinical Oncology Annual Meeting and published in the Journal of Clinical Oncology, supporting the recent supplemental Biologics License Application submission to the U.S. Food and Drug Administration. The therapy represents the first subcutaneous dual EGFR- and MET-targeting inhibitor evaluated in this setting. The confirmed overall response rate of 42 percent exceeded the response rates rarely exceeding 24 percent seen with current options after immunotherapy and chemotherapy, with a clinical benefit rate of 63 percent. Median time to first response was 6.6 weeks, and median progression-free survival and overall survival reached 6.8 months and 12.5 months, respectively.

Phase 1b/2 Trial Design and Patient Population in OrigAMI-4 Study

Cohort 1 enrolled 102 patients with recurrent or metastatic head and neck squamous cell carcinoma who had received prior PD-1/PD-L1 immunotherapy and platinum-based chemotherapy, excluding those with human papillomavirus-positive oropharyngeal cancer or prior anti-EGFR therapy. Treatment followed an initial loading phase with subsequent dosing every three weeks, and the primary endpoint was overall response rate assessed by investigators and confirmed via blinded independent central review. The study design incorporated weight-based dosing and aligned with Response Evaluation Criteria in Solid Tumors version 1.1 for response assessment. Ongoing evaluation in the Phase 3 OrigAMI-5 trial explores the agent in combination with carboplatin and pembrolizumab as first-line therapy.

Potential Shifts in Treatment Paradigms for Metastatic Head and Neck Squamous Cell Carcinoma

Up to half of patients with head and neck squamous cell carcinoma experience recurrence or metastatic disease, with five-year survival approximately 15 percent once the disease reaches this stage, underscoring persistent unmet need. The observed complete response rate and durability of responses with subcutaneous amivantamab monotherapy suggest opportunities to improve expectations for patients facing limited current options. These clinical outcomes, combined with the convenience of subcutaneous administration and established manageable safety profile, may inform value assessments in Health Economics and Outcomes Research (HEOR) by highlighting differentiated efficacy in a population with high disease burden. The supplemental Biologics License Application submission positions the therapy for potential integration into market access and reimbursement frameworks once approved.