Why it matters: The results suggest that a chemotherapy-free combination could challenge existing first-line treatments for head and neck squamous cell carcinoma (HNSCC), a disease historically associated with median survival of about 10–12 months after recurrence or metastasis, according to Genmab. Everett Vokes of University of Chicago Medicine called the LiGeR-HN1 trial “the first positive Phase 3 study in this patient population in several years” in the company’s press release.
Barbara Burtness, a Yale Cancer Center oncologist and first author of the KEYNOTE-048 Phase 3 report that helped establish pembrolizumab-based treatment, told European Biotechnology that available evidence does not suggest chemotherapy adds as much to Keytruda as petosemtamab did. “It seems likely that pembrolizumab plus petosemtamab will emerge as an important first-line regimen in head and neck cancer,” she said.
Following the Phase 3 announcement, Genmab’s shares surged 29% on Wednesday and reached an intraday high of DKK 3,928 (€526) on Friday, approximately 31% above their pre-announcement closing price.
By the numbers: LiGeR-HN1 met both primary endpoints, overall survival and objective response rate, at a first interim analysis.
- The hazard ratio for death was 0.50, and the combination more than tripled the odds of an objective response (odds ratio 3.17). Genmab said both endpoints were met regardless of human papillomavirus (HPV) status.
- Genmab said the combination was generally well tolerated, with no new safety signals.
How it works: Petosemtamab binds EGFR, a growth-signal receptor on tumor cells, and LGR5, which Genmab says is found on stem-like cancer cells implicated in treatment resistance and recurrence.
“EGFR is an established therapeutic target in head and neck cancer,” Jennifer Grandis, a prominent HNSCC researcher and a professor of otolaryngology at the University of California, San Francisco, told European Biotechnology.
“Targeting EGFR with a monoclonal antibody (cetuximab) was proven efficacious and was FDA-approved in 2006. However, despite high expression of the target, only a subset of patients respond to this agent. LGR5 is also expressed by stem cells in many cancers, including head and neck cancer. Targeting stem cells alone has proven difficult. Petosematamab is a bi-specific antibody that targets both EGFR and LGR5. The immune impact appears to be largely through increased ADCC,” she added, referring to immune cells killing antibody-coated tumor cells.
Backstory: When Genmab agreed to buy Merus in September 2025, the first-line combination had shown a 63% response rate in a small, single-arm Phase 2 study, but median overall survival had not yet been reached. In updated results presented at ESMO in October 2026, median overall survival was 28.2 months.
Reality check: The results come from a first interim analysis, and Genmab has yet to report median overall survival, absolute response rates or detailed safety data. These will help establish the full clinical significance of the survival benefit.
LiGeR-HN1 is open-label and compared the combination with Keytruda alone, although in the EU Keytruda is also approved with platinum and 5-fluorouracil chemotherapy for these first-line patients.
Burtness noted that Keytruda alone and Keytruda plus chemotherapy have not been compared in a statistically powered head-to-head trial in this setting.
The competition: Boston-based Bicara Therapeutics expects interim results in mid-2027 from a double-blind trial adding its EGFR- and TGF-beta-targeting ficerafusp alfa to Keytruda in first-line, HPV-negative disease.
What’s next: Genmab plans to engage regulators and submit the full results to a medical meeting. The company said in December 2025 that it expected to launch petosemtamab in 2027, subject to clinical results and regulatory approval.
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