Genmab: Petosemtamab plus pembrolizumab yields 28.2‑month median OS in 1L PD‑L1+ r/m HNSCC

Key efficacy findings

In the Phase 2 first‑line combination arm of petosemtamab plus pembrolizumab for PD‑L1+ recurrent/metastatic head and neck squamous cell carcinoma, median overall survival was 28.2 months (efficacy‑evaluable n=43). The overall response rate was 63%, including a 19% complete response rate, and median progression‑free survival was 9.0 months (95% CI 5.2–12.9). The 12‑month OS rate was 79% and the 12‑month PFS rate was 40%.

Durability

With a median duration of follow‑up of 25.5 months (as of May 15, 2026), median duration of response was not reached; an estimated 55% of responders maintained response at 24 months.

Safety profile

The most common treatment‑emergent adverse events were asthenia (51%), acneiform dermatitis (51%) and rash (49%). Infusion‑related reactions occurred in 38% of patients (7% Grade 3–4) and resolved; no Grade 5 events or treatment‑related deaths were reported.

Trial design and development program

The data come from an ongoing open‑label, multicenter Phase 2 study (NCT03526835). In the first‑line combination cohort, 45 patients received 1500 mg petosemtamab every two weeks plus 400 mg pembrolizumab every six weeks until progression or unacceptable toxicity. Petosemtamab is a bispecific antibody targeting EGFR and LGR5 and is being advanced into four Phase 3 LiGeR trials across head and neck and colorectal cancer indications.