Genmab reported, that the petosemtamab, an investigational IgG1-bispecific antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5), in combination with pembrolizumab versus pembrolizumab met both primary endpoints, overall survival and objective response rate, at an interim analysis assessed by an independent data monitoring committee.
The company reported benefit regardless of human papillomavirus (HPV) status. The announcement provided topline estimates, with the full results planned for submission to a future medical meeting.
Adding petosemtamab to pembrolizumab halved the hazard of death versus pembrolizumab alone at the first interim analysis of the Phase 3 LiGeR-HN1 trial, a result that could expand first-line chemotherapy-free options for patients with PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Commenting on the Phase 3 LiGeR-HN1 topline results, Jan van de Winkel, Chief Executive Officer of Genmab, said:
“These topline Phase 3 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.”
Van de Winkel said the findings marked a step toward potentially bringing petosemtamab to patients with recurrent or metastatic head and neck cancer. He added that Genmab plans to engage with regulatory authorities globally and share the full dataset with the medical community.
LiGeR-HN1 Meets Both Primary Endpoints
- Overall survival (OS) – The hazard ratio for death was 0.50 (95% CI, 0.37–0.67; P < .0001), corresponding to a 50% lower hazard of death with the combination. The announcement did not report median OS or survival rates at specific time points, so the absolute survival gain remains unknown.
- Objective response rate (ORR) – The odds ratio was 3.17 (95% CI, 2.06–4.89; P < .0001), indicating more than threefold higher odds of objective response with the combination. Arm-specific response rates were not disclosed.
- HPV status – Genmab reported benefit regardless of HPV status. The release did not provide subgroup-specific effect estimates.
- Safety – Genmab described the combination as generally well tolerated, with a safety profile consistent with those previously reported for the individual agents. The company reported no new safety signals. Detailed adverse event rates were not disclosed.
A Direct Comparison With Pembrolizumab Alone
LiGeR-HN1 is a randomized, open-label, global, multicenter Phase 3 study in patients receiving first-line treatment for recurrent or metastatic PD-L1-positive HNSCC. Patients were randomized 1:1 to receive petosemtamab plus pembrolizumab or pembrolizumab alone.
The study’s key secondary endpoints include progression-free survival, duration of response, time to response, safety and patient-reported outcomes. These measures will help clinicians judge how quickly patients respond, how long responses last and what adding petosemtamab means for patients’ daily lives.
Everett E. Vokes, Chair, Department of Medicine and Physician-in-Chief, University of Chicago Medicine, highlighted the urgency behind the trial:
“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.”
How Petosemtamab Targets EGFR and LGR5
Petosemtamab (GEN1158) is an investigational, fully human IgG1 bispecific antibody that binds epidermal growth factor receptor (EGFR) and leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). LGR5 is expressed on a population of cancer stem-like cells implicated in tumor initiation, treatment resistance and recurrence.
Binding to EGFR blocks ligand binding and inhibits EGFR signaling regardless of LGR5 expression. In tumor cells that express both targets, simultaneous binding uses LGR5’s natural internalization process to promote EGFR degradation. The antibody’s active Fc domain can also recruit innate immune cells, including natural killer cells, to kill tumor cells through antibody-dependent cell-mediated cytotoxicity.
About Head and Neck Squamous Cell Carcinoma
Head and neck squamous cell carcinoma (HNSCC) encompasses a group of biologically similar cancers that arise in the tissues lining the oral cavity, pharynx and larynx. HNSCC accounts for more than 90% of all head and neck cancers.It ranks as the seventh most common cancer worldwide, and the risk is approximately two to four times higher in men than in women.
Treatment options depend on the tumor’s location and stage, as well as the patient’s overall health. Despite available treatments, approximately 50% of patients with locally advanced HNSCC experience recurrence after initial treatment, underscoring the need for additional therapies.
What the Full Dataset Needs to Clarify
The interim survival result makes petosemtamab plus pembrolizumab a candidate for an additional first-line chemotherapy-free option. For oncology teams weighing its potential role, the next dataset will need to show the absolute survival gain, response durability, adverse event rates and patient-reported outcomes. LiGeR-HN1 used pembrolizumab monotherapy as its comparator, so it provides no head-to-head estimate against pembrolizumab plus chemotherapy.
The Phase 3 program also includes LiGeR-HN2 in second- and third-line recurrent or metastatic HNSCC and LiGeR-CRC1 and LiGeR-CRC2 in previously treated colorectal cancer. Those trials will address separate questions about petosemtamab’s role beyond the first-line head and neck cancer setting.
Petosemtamab remains investigational. The FDA previously granted Breakthrough Therapy Designation for the combination in first-line recurrent or metastatic PD-L1-positive HNSCC. Genmab plans to engage global regulatory authorities and submit the full LiGeR-HN1 results for presentation at a future medical meeting.
You can also read: OrigAMI-4 at ESMO 2026: Amivantamab Plus Pembrolizumab and Carboplatin Shows 77% Response Rate in Head and Neck Cancer.
