Genmab’s petosemtamab, an investigational IgG1-bispecific antibody, plus Keytruda (pembrolizumab) reduced the risk of death by 50% in a Phase III trial in patients with first-line (1L) PD-L1-positive recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
In the open-label LiGeR-HN1 trial (NCT06525220), Genmab pitted the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5) targeting bispecific plus MSD’s Keytruda against Keytruda alone in 699 patients. In the first interim analysis, as assessed by an independent data monitoring committee (IDMC), treatment with the combination demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), reducing the risk of death by 50%, and objective response rate (ORR) with an odds ratio of 3.17, meeting its dual primary endpoints, regardless of human papillomavirus (HPV) status.
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The safety profile of the combination was generally well tolerated and consistent with the previously reported safety profiles of the individual agents.
Dr Everett Vokes, chair, Department of Medicine and Physician-in-Chief, University of Chicago Medicine, said: “Patients with recurrent or metastatic head and neck cancer face a disease that can profoundly affect both survival and some of the most essential aspects of daily life, making progress in treatment urgently needed. As the first positive Phase III study in this patient population in several years, LiGeR-HN1 represents a major milestone with the potential to redefine care.
“Meeting its dual primary endpoints of overall survival and objective response rate at the first interim analysis underscores the potential of petosemtamab plus Keytruda to transform first-line treatment for patients with PD-L1-positive disease, regardless of HPV status. These results suggest this chemotherapy-free combination could reshape the treatment of this devastating disease by establishing a new therapeutic option,” Vokes added.
Based on the topline results, Genmab plans to engage global regulatory authorities and will present full LiGeR-HN1 data at a future medical meeting.
Beyond LiGeR-HN1, petosemtamab is also being evaluated in the Phase III LiGeR-HN2 study (NCT06496178) in patients with second- and third-line recurrent/metastatic HNSCC, and two Phase III studies, LiGeR-CRC1 (NCT07702032) and LiGeR-CRC2 (NCT07775287), in patients with previously treated, recurrent, unresectable ormetastatic colorectal cancer.
Keytruda was the most recent drug to gain US approval in this indication on 12 June 2025 and can be used as a neoadjuvant and adjuvant treatment of resectable locally advanced HNSCC expressing PD-L1.
This data comes just three days after Johnson & Johnson’s (J&J’s) Rybrevant Faspro combination showed success in patients with recurrent or metastatic HNSCC. J&J presented the data during the European Society of Medical Oncology (ESMO) Congress 2026.
Investors and analysts delighted with data
William Blair analysts touted these results as “exceptional”, adding that it was notable that the benefit was observed regardless of HPV status, as this had been “an ongoing concern for investors”. Analysts added that they now await median OS, ORR, and PFS data, but continue to agree that the first interim analysis is “an exceedingly positive top-line outcome” and “meaningfully strengthens the case for petosemtamab plus Keytruda as the new standard-of-care regimen in 1L PD-L1+ HNSCC”.
The company’s stock also rose on the news. On its primary listing on the Nasdaq Copenhagen, the company’s stock was up 29.06%, from a 27 October close of DKr2997.00 to a 28 October close of DKr3868.00. On the New York Nasdaq, the company saw a similar rise, 28.25%, from a 27 October close of $44.67 to a 28 October close of $57.29.
For a roundup of the key readouts at this year’s ESMO 2026 meeting, you can listen to our podcast here.
