Petosemtamab Plus Pembrolizumab Significantly Improves Overall Survival in Patients With Head and Neck Squamous Cell Carcinoma

Clinical Summary:

• Design/Population: The phase 3 LiGeR-HN1 trial evaluated petosemtamab, an EGFR/LGR5-targeting bispecific antibody, plus pembrolizumab versus pembrolizumab alone as first-line treatment for patients with PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma.
• Key Outcomes: The combination met both primary end points, significantly improving overall survival and objective response rate compared with pembrolizumab alone. The combination reduced the risk of death by 50%, with benefits reported regardless of HPV status. No new safety signals were identified.
• Clinical Relevance: These findings support petosemtamab plus pembrolizumab as a potential chemotherapy-free first-line treatment option for patients with PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma. 

Topline results from the phase 3 LiGeR-HN1 trial demonstrated that petosemtamab plus pembrolizumab significantly improved overall survival (OS) and objective response rate (ORR) compared with pembrolizumab alone in patients with PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), supporting the chemotherapy-free combination as a potential new first-line treatment option. 

In this multicenter, open-label trial, patients were randomized 1:1 to receive either petosemtamab plus pembrolizumab or pembrolizumab alone. Primary end points included OS and ORR. Key secondary end points included progression-free survival (PFS), duration of response, time to response, safety, and patient-reported outcomes.

At the first interim analysis, assessed by an independent data monitoring committee, petosemtamab plus pembrolizumab significantly improved OS compared with pembrolizumab alone, reducing the risk of death by 50% (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.37 to 0.67; P < .0001). A significant improvement in ORR was also observed with the combination (odds ratio, 3.17; 95% CI, 2.06 to 4.89; P < .0001). 

The survival and response benefits were observed regardless of human papillomavirus (HPV) status.

No new safety signals identified and the safety profile of petosemtamab plus pembrolizumab was reported to be generally well tolerated and consistent with the previously reported safety profiles of the individual agents.

Detailed adverse event rates, including grade ≥3 toxicities and treatment discontinuations, were not provided in the topline announcement.

“Meeting its dual primary end points of OS and ORR at the first interim analysis underscores the potential of petosemtamab plus pembrolizumab to transform first-line treatment for patients with PD-L1-positive disease, regardless of HPV status,” stated Everett Vokes, MD, University of Chicago Medicine, Chicago, Illinois. “These results suggest this chemotherapy-free combination could reshape the treatment of this devastating disease by establishing a new therapeutic option.”

Based on these findings, Genmab plans to engage global regulatory authorities regarding the potential approval of petosemtamab plus pembrolizumab and submit the complete LiGeR-HN1 results for presentation at a future medical meeting. 

Petosemtamab previously received FDA Breakthrough Therapy Designation in combination with pembrolizumab for the first-line treatment of PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma, as well as for recurrent or metastatic head and neck squamous cell carcinoma following platinum-based chemotherapy and anti-PD-1 therapy.

The findings support further development of petosemtamab plus pembrolizumab as a potential chemotherapy-free first-line treatment option for patients with PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma, pending full efficacy and safety results and regulatory review.

Source:

Genmab. 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. Accessed on October 30, 2026. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-statistically-significant-clinically-meaningful/