Genmab Reports 28.2-Month Median OS With Petosemtamab in HNSCC

COPENHAGEN, Denmark — October 26, 2026

Petosemtamab Combination Shows Antitumor Activity

As of May 15, 2026, the combination arm reported a median OS of 28.2 months, with a 12-month OS rate of 79%. Median PFS was 9.0 months (95% confidence interval [CI], 5.2–12.9), and the 12-month PFS rate was 40%. The ORR was 63%, including complete responses in 19% of efficacy-evaluable patients. Median DOR had not been reached at the data cutoff, and the estimated proportion of responders maintaining a response at 24 months was 55%. These endpoints provide different perspectives on treatment activity: OS measures time until death, PFS measures time until disease progression or death, ORR captures the proportion of patients with a defined tumor response, and DOR assesses how long responses persist. The reported results indicate that some patients experienced sustained responses, while the median PFS shows that disease progression remained a concern during follow-up. Clinical activity was observed across PD-L1 CPS and p16 subgroups, including HPV-positive and HPV-negative disease. These findings may be relevant because HNSCC includes biologically distinct tumors and patient outcomes can vary by disease characteristics. Nevertheless, subgroup observations from a small Phase 2 cohort should be interpreted cautiously and are not sufficient to establish consistent efficacy across all patient groups. The study included 45 treated patients in the first-line combination arm, while the headline efficacy measures were reported for 43 efficacy-evaluable patients. Patients received petosemtamab at 1,500 mg every two weeks plus pembrolizumab at 400 mg every six weeks until disease progression or unacceptable toxicity. The study is ongoing and evaluates petosemtamab both as monotherapy and in combination with pembrolizumab across HNSCC and other solid tumors. The current results provide a clinical rationale for continued investigation but require confirmation in larger, controlled Phase 3 studies.

Safety Profile and Potential Biological Mechanisms

The combination’s safety findings were described as manageable in the reported Phase 2 population. The most common treatment-emergent adverse events (TEAEs), including all grades and Grade 3–4 events, were asthenia at 51% and 7%, acneiform dermatitis at 51% and 7%, and rash at 49% and 2%, respectively. Infusion-related reactions occurred in 38% of patients, with Grade 3–4 reactions reported in 7%. All reported infusion-related reactions resolved. Genmab reported no Grade 5 adverse events and no treatment-related deaths in the combination arm. These results provide an initial overview of tolerability as follow-up becomes more mature, although they do not replace a complete assessment of treatment risks or establish how the combination compares with other treatment options. The frequency of skin-related adverse events and infusion reactions is relevant to clinical monitoring, and ongoing studies will provide additional information about the safety profile with longer exposure and larger patient populations. Petosemtamab, also known as GEN1158, is an investigational human IgG1-based bispecific antibody designed to target both epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5). Its proposed mechanisms include inhibiting EGFR-mediated signaling, promoting EGFR degradation in cancer stem-like cells expressing both EGFR and LGR5, and supporting innate immune-mediated activity through interactions with macrophages and natural killer cells. Genmab describes this combination of mechanisms as a potential way to address tumor growth and cells associated with recurrence. These mechanisms remain under clinical investigation, and their contribution to the observed patient outcomes has not been independently established by the reported Phase 2 results. Petosemtamab is not approved for marketing and should be considered an investigational treatment.

Genmab Advances Phase 3 LiGeR Clinical Program

Genmab is advancing petosemtamab through a broader clinical development program, including four Phase 3 LiGeR trials across head and neck squamous cell carcinoma and colorectal cancer. LiGeR-HN1 is evaluating petosemtamab in first-line PD-L1-positive recurrent or metastatic HNSCC, while LiGeR-HN2 is investigating the candidate in second- and third-line recurrent or metastatic HNSCC. The program also includes LiGeR-CRC1, studying first-line treatment in RAS/BRAF wild-type, left-sided unresectable or metastatic colorectal cancer, and LiGeR-CRC2, evaluating second-line treatment in RAS/BRAF wild-type recurrent, unresectable or metastatic colorectal cancer. The Phase 3 first-line HNSCC program remains ongoing, with topline data anticipated later in 2026, according to the company. Those results will be important for determining whether the encouraging survival and response findings from Phase 2 can be confirmed in a larger study designed to assess treatment outcomes more rigorously. The ongoing clinical program also reflects Genmab’s strategy of evaluating antibody-based therapies across multiple solid tumors. The updated Phase 2 data provide a signal of potentially meaningful activity for petosemtamab plus pembrolizumab in first-line PD-L1-positive r/m HNSCC, including a median OS exceeding two years and responses observed across HPV and p16 subgroups. However, the absence of a randomized comparator in the reported Phase 2 findings, the small efficacy-evaluable population and the need for further follow-up limit conclusions about comparative benefit. Results from the ongoing Phase 3 program will be central to determining the treatment’s potential role in clinical practice.

Source:Genmab ,Press release