The addition of the bispecific antibody petosemtamab (MCLA-158) to pembrolizumab (Keytruda) led to significant improvements in overall survival (OS) and objective response rate (ORR) compared with pembrolizumab monotherapy as first-line treatment for patients with PD-L1–positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), meeting both primary end points of the phase 3 LiGeR-HN1 trial (NCT06525220).1
Findings announced by Genmab showed that at the first interim analysis, the combination reduced the risk of death by 50% compared with pembrolizumab alone (HR, 0.5; 95% CI, 0.37–0.67; P < .0001). The ORR odds ratio was 3.17 (95% CI, 2.06–4.89; P < .0001). The OS and ORR benefits were observed irrespective of human papillomavirus (HPV) status.
The combination was generally well tolerated, with a safety profile in line with what has been documented for each agent individually and no new safety signals observed.
Data from LiGeR-HN1 will be submitted for presentation at a future medical meeting and shared with global health authorities.
“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 3 study in this patient population in several years, LiGeR-HN1 represents a major milestone with the potential to redefine care,” Everett E. Vokes, MD, chair of the Department of Medicine and physician-in-chief at University of Chicago Medicine, stated in a news release. “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. These results suggest this chemotherapy-free combination could reshape the treatment of this devastating disease by establishing a new therapeutic option.”
Petosemtamab is an investigational immunoglobulin G1 bispecific antibody directed against EGFR and LGR5, with a design intended to exert antitumor activity through 3 complementary mechanisms.
By preventing ligands from binding to EGFR, the agent shuts down downstream signaling pathways that drive tumor growth. Because it engages EGFR and LGR5 simultaneously, petosemtamab also triggers EGFR internalization and degradation in cells that express both receptors, an effect aimed at LGR5-positive cancer cells with stem-like properties.
The global, multicenter, open-label LiGeR-HN1 study randomly assigned patients 1:1 to receive petosemtamab plus pembrolizumab or pembrolizumab alone.
To enroll, patients needed to be at least 18 years of age with recurrent or metastatic HNSCC that could not be treated with curative-intent local therapy.2 Other key inclusion criteria comprised a PD-L1 combined positive score of 1 or higher, no prior systemic therapy in the incurable recurrent or metastatic settings, an ECOG performance status of 0 or 1, and measurable disease per RECIST 1.1 criteria.
OS and ORR by blinded independent central review per RECIST criteria 1.1 served as the dual primary end points, with assessment windows of up to approximately 3 years and 2 years, respectively. Secondary end points included progression-free survival, duration of response, clinical benefit rate, and time to response.
“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,” Jan van de Winkel, PhD, chief executive officer of Genmab, added in a news release.1 “Meaningful innovation is measured not only by scientific discovery, but by its potential to improve outcomes for patients. The LiGeR-HN1 topline findings mark an important step toward potentially bringing petosemtamab to patients with recurrent or metastatic head and neck cancer, and we look forward to engaging with regulatory authorities globally and sharing the full dataset with the medical community.”
