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# Genmab's Antibody Halves Death Risk in Head and Neck Cancer
- URL: https://bioweek.com/genmabs-antibody-halves-death-risk-in-head-and-neck-cancer/
- Published: 2026-10-30T06:06:37.000Z
- Updated: 2026-10-30T06:06:37.000Z
- Description: Petosemtamab plus Keytruda halved the risk of death versus Keytruda alone in first-line PD-L1-positive head and neck cancer, the first positive Phase 3 in that setting in several years, as Genmab races to replace Darzalex royalties.
- Author: BioWeek
- Tags: Pipeline, Science, Markets

Petosemtamab plus Merck's Keytruda cut the risk of death in half versus Keytruda alone in first-line PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma, Genmab said in an Oct. 28 company [announcement](https://ir.genmab.com/news-releases/news-release-details/genmab-announces-statistically-significant-clinically-meaningful/?ref=bioweek.com). At a first interim analysis of the Phase 3 LiGeR-HN1 [trial](https://clinicaltrials.gov/study/NCT06525220?ref=bioweek.com), an independent data monitoring committee reported an overall survival hazard ratio of 0.50 (95% CI 0.37-0.67, p<0.0001), a 50% reduction in the risk of death. The combination also met the co-primary objective response rate endpoint, with an odds ratio of 3.17 (95% CI 2.06-4.89, p<0.0001). Both endpoints held regardless of HPV status.

### A survival signal with an incomplete picture

Overall survival is the hard endpoint in this disease. Recurrent or metastatic HNSCC still carries a median overall survival of roughly 10-12 months, and about 50% of patients with locally advanced HNSCC recur after initial treatment. Investigator Everett Vokes, MD, chair of the Department of Medicine at University of Chicago Medicine, called the study the first positive Phase 3 in this patient population in several years and flagged the potential for a chemotherapy-free first-line option.

That is the clinical and commercial hook. Pembrolizumab monotherapy is already a first-line standard in PD-L1-positive disease. Adding a bispecific without chemotherapy, if the full dataset holds up under review, would be a meaningful shift in how these patients are treated. The trial was randomized 1:1, open-label, global, and multicenter. The open-label design leaves room for bias on softer measures, and the response-rate result is reported only as an odds ratio at this first interim look, not as a raw percentage. Until Genmab presents the full results at a medical meeting, the size of the tumor-shrinkage effect remains unknown even as the survival result looks unusually clean.

Safety was described as generally well tolerated and consistent with the previously reported profiles of each agent. No new safety signals were identified. Petosemtamab (GEN1158) is an investigational fully human IgG1 bispecific antibody, low-fucose with an active Fc domain, targeting both EGFR and LGR5\. LGR5 marks cancer stem-like cells implicated in tumor initiation, treatment resistance, and recurrence. The antibody is designed to block EGFR signaling, drive EGFR degradation when LGR5 and EGFR are co-expressed, and trigger antibody-dependent cell-mediated cytotoxicity through natural killer cells. It already holds FDA Breakthrough Therapy Designation for first-line recurrent or metastatic PD-L1-positive HNSCC in combination with pembrolizumab. Genmab plans to engage global regulatory authorities and will submit the full results for presentation at a future medical meeting.

### The Merus purchase now has a Phase 3 anchor

In October 2025 Genmab agreed to [acquire](https://ir.genmab.com/news-releases/news-release-details/genmab-acquire-merus-expanding-late-stage-pipeline-and/?ref=bioweek.com) Merus, the Dutch biotech that originated petosemtamab, for $97.00 per share in an all-cash transaction valuing the deal at approximately $8.0 billion. LiGeR-HN1 is the first large payoff from that purchase. The franchise is not a one-trial story. Genmab is also running LiGeR-HN2 in second- and third-line HNSCC, plus LiGeR-CRC1 and LiGeR-CRC2 in colorectal cancer. A chemotherapy-free, HPV-agnostic first-line win in head and neck cancer is the near-term filing case. The colorectal studies are the longer optionality that has to justify an $8 billion check if HNSCC alone cannot.

### Three late-stage wins against a royalty cliff

BioPharma Dive reported that this is Genmab's [third](https://www.biopharmadive.com/news/genmab-stock-soars-positive-head-neck-cancer-antibody-phase-3/873164/?ref=bioweek.com) consecutive positive late-stage readout in a few weeks. Epkinly, partnered with AbbVie, succeeded in a Phase 3 study in frontline diffuse large B-cell lymphoma. Rinatabart sesutecan, an antibody-drug conjugate from Genmab's 2024 acquisition of ProfoundBio, hit its goal in a late-stage ovarian cancer study. The streak matters because Genmab is racing to replace revenue from Darzalex (daratumumab), the multiple myeloma drug whose commercial rights belong to Johnson & Johnson and on which Genmab earns royalties. Darzalex exclusivity is approaching expiry. Genmab booked roughly $3.7 billion in revenue in 2025, heavily from those royalties.

On the LiGeR-HN1 news, BioPharma Dive said Genmab's market value rose by more than $7 billion, pushing its worth past $35 billion. Analysts at TD Cowen (Yaron Werber) and William Blair (Matt Phipps) framed the results as supporting a potential broad label regardless of HPV status and positioning Genmab to surpass $10 billion in annual revenue. That is an analyst case, not a company forecast, and it assumes regulators, payers, and the remaining petosemtamab program all cooperate.

The tension is timing. An OS hazard ratio of 0.50 in first-line PD-L1-positive HNSCC is the kind of result that can support a filing. An open-label design and an ORR reported only as an odds ratio mean the medical-meeting presentation still has to fill in the picture. Darzalex royalties will not wait for a perfect dataset. Petosemtamab now has to carry a large share of the growth story Genmab is trying to tell after the cliff.