Amivantamab Plus Pembrolizumab in Previously Untreated Recurrent/Metastatic Head & Neck Squamous Cell Cancer: Results From the Phase 1b/2 OrigAMI-4 Study

Journal

International Journal of Radiation Oncology, Biology, Physics

Year

2026

Materials & Methods

Cohort 2 of the OrigAMI-4 study (NCT06385080) is evaluating amivantamab plus pembrolizumab in HPV-unrelated, previously untreated PD-L1 CPS ≥1 R/M HNSCC. Subcutaneous amivantamab was dosed weekly for the first 3 weeks (first dose only: 1600 mg [2240 mg for ≥80 kg]; subsequent doses: 2400 mg [3360 mg for ≥80 kg]), then Q3W at 2400 mg (3360 mg for ≥80 kg) thereafter. Pembrolizumab was dosed intravenously at 200 mg Q3W. Primary endpoint is objective response rate (ORR) per RECIST v1.1.

Results

As of 9 Sep 2025, the cohort was fully enrolled; 39 pts have received amivantamab plus pembrolizumab. Median age was 63 years, 85% were male, and 56% had ECOG performance status score of 1. At a median follow-up of 6.7 months (range, 1.6–9.2), median treatment duration was 5.6 months (range, 0.7–9.2), with 69% of pts remaining on treatment. The confirmed ORR was 49% (19/39; 95% CI, 32–65); there were 4 complete and 15 partial responses, with 2 additional responses pending confirmation. Clinical benefit rate (confirmed responder or durable stable disease) was 72% (28/39; 95% CI, 55–85), and 82% (32/39) had tumor shrinkage of target lesions. Median time to first response was 9.4 weeks (range, 8.7–21.1). Responses are ongoing in 89% (17/19) of confirmed responders. Median duration of response was not estimable. Progression-free survival and overall survival data are immature. Most common treatment-emergent AEs (>30%) were rash, paronychia, dermatitis acneiform, alanine aminotransferase increased, hypoalbuminemia, and stomatitis. Administration-related reactions were seen in 7 (18%) pts (none grade ≥3). Two pts discontinued treatment due to amivantamab-related AEs. Updated results with longer follow-up will be presented at the meeting.

Conclusion

Treatment with amivantamab plus pembrolizumab in the first-line R/M setting for HPV-unrelated HNSCC demonstrated clinically meaningful and durable antitumor activity, including 10% of pts achieving a complete response. The safety profile was consistent with those of the individual agents, with no new safety signals identified.

Resources and Links

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https://www.redjournal.org/article/S0360-3016(26)00182-3/abstract

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