Genmab Combo Lowers Death Risk 50% in Advanced Head and Neck Cancer

Genmab said on October 28 that its experimental antibody petosemtamab, given with the immunotherapy pembrolizumab, cut the risk of death by 50% compared with pembrolizumab alone in a phase 3 trial. The study, LiGeR-HN1, tested the pair as a first treatment for head and neck cancer that has come back or spread.

What happened

LiGeR-HN1 is a global, open-label phase 3 study. Adults with recurrent or metastatic head and neck squamous cell carcinoma whose tumours test positive for PD-L1 were randomized 1:1 to the combination or to pembrolizumab on its own.

At the first interim analysis, the trial met both of its main goals, according to the company:

• Overall survival: a hazard ratio of 0.50, which means a 50% lower risk of death (p<0.0001).
• Response rate: an odds ratio of 3.17 in favour of the combination (p<0.0001).
• HPV status: the benefit held whether or not tumours were linked to HPV.

Genmab said the combination was generally well tolerated and no new safety signals appeared. It did not give median survival, the number of patients or progression-free survival, BioPharm International reported. The full results will be submitted to a future medical meeting.

Why it matters

Head and neck squamous cell carcinoma makes up more than 90% of head and neck cancers. Once it recurs or spreads, median survival is about 10 to 12 months, according to BioPharm International.

Everett Vokes, physician-in-chief at University of Chicago Medicine, said in Genmab's release that this is the first positive phase 3 study in this group of patients in several years. The combination does not use chemotherapy.

Petosemtamab is a bispecific antibody that targets two proteins, EGFR and LGR5. It already holds two FDA Breakthrough Therapy designations in head and neck cancer. CEO Jan van de Winkel called the results a defining milestone and said Genmab sees the drug as a potential first-in-class treatment.

The result also tests a large bet. Genmab gained the drug by buying Merus, a deal announced in September 2025 at $97 per share in cash, about $8.0 billion in equity value.

What it means for people in the industry

Genmab said it plans to talk with regulators around the world. It has not given a filing date.

Things to watch:

• The full data, including median survival and safety details, at a medical meeting.
• Whether Genmab files with the FDA and other regulators, and when.
• Results from LiGeR-HN2 in later-line head and neck cancer and from two colorectal cancer trials.

Petosemtamab remains an investigational drug.

See open pharma jobs in the US and Canada

Sources

• Genmab Announces Statistically Significant, Clinically Meaningful Improvement in Overall Survival and Objective Response with Petosemtamab Combination at First Interim Analysis in First-Line R/M Patients with PD-L1+ Head and Neck Cancer, Genmab (via Ritzau)
• Genmab's Petosemtamab Plus Pembrolizumab Cuts Risk of Death by 50% in Phase 3 Head and Neck Cancer Trial, BioPharm International
• Petosemtamab Plus Pembrolizumab Hits Phase 3 OS, ORR Primary End Points in PD-L1+ R/M HNSCC, OncLive