Genmab announced positive topline results on October 28 from LiGeR-HN1, its global Phase 3 trial of petosemtamab in combination with pembrolizumab against pembrolizumab alone, in first line treatment of PD-L1 positive recurrent or metastatic head and neck squamous cell carcinoma. At the first interim analysis, assessed by an independent data monitoring committee, the combination met both dual primary endpoints. Overall survival gave a hazard ratio of 0.50, with a 95 percent confidence interval of 0.37 to 0.67 and p below 0.0001, which the company describes as a 50 percent reduction in the risk of death. Objective response gave an odds ratio of 3.17, with a 95 percent confidence interval of 2.06 to 4.89 and p below 0.0001. Both results held regardless of HPV status.
Petosemtamab is an investigational bispecific antibody targeting EGFR and LGR5. The trial, registered as NCT06525220, is randomized, open label and multicenter, and compares the combination directly against pembrolizumab, the immunotherapy that anchors current first line care in this population. That active comparator matters: the survival claim is not drawn from a single arm series but from a randomized test of what adding petosemtamab does to the standard.
The company said the safety profile of the combination was generally well tolerated and consistent with the previously reported profiles of the two agents, with no new safety signals identified. Everett Vokes of the University of Chicago Medicine, quoted in the release, called it the first positive Phase 3 study in this patient population in several years and a potential milestone for redefining care. Chief executive Jan van de Winkel called the results a defining milestone for Genmab.
What is missing is as important as what landed. Genmab released hazard and odds ratios but no median overall survival, no absolute response rates and no detailed adverse event tables, so the size of the benefit in months and the cost of the combination in toxicity cannot yet be judged. The company plans to engage global regulatory authorities and to submit the full results for presentation at a future medical meeting.
Petosemtamab is also in Phase 3 testing in second and third line head and neck cancer in LiGeR-HN2, and in two Phase 3 studies in previously treated colorectal cancer. This site covered a Phase 2 colorectal readout for the same drug on October 26; the head and neck Phase 3 result is a separate and larger claim, and it is the one that will decide the drug’s first approval path.