At the first interim analysis, the combination cut the risk of death by 50 percent compared with pembrolizumab alone (hazard ratio 0.50; p<0.0001). Patients were also more likely to respond to treatment, with an odds ratio for objective response of 3.17 (p<0.0001). Both endpoints were met regardless of HPV status. According to the company, the combination was generally well tolerated, with a safety profile in line with what is known for each drug and no new safety signals.

Petosemtamab is an investigational IgG1 bispecific antibody targeting EGFR and LGR5. It holds FDA Breakthrough Therapy Designation in first-line PD-L1-positive head and neck cancer in combination with pembrolizumab. Patients with recurrent or metastatic disease currently have a median overall survival of around 10–12 months. Genmab is also testing petosemtamab in the Phase 3 LiGeR-HN2 trial in later-line head and neck cancer, and in two Phase 3 trials in metastatic colorectal cancer.

Genmab plans to engage with regulatory authorities globally and will present the full results at an upcoming medical meeting.

“These topline Phase III results represent a defining milestone for Genmab and further strengthen our conviction in petosemtamab as a potential first-in-class treatment option for patients with this difficult-to-treat cancer,” says Jan van de Winkel, CEO of Genmab.