Genmab Announces Updated Phase 2 Data Demonstrating More Than Two-Year Median Overall Survival with Petosemtamab Plus Pembrolizumab in First-Line Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Media Release
COPENHAGEN, Denmark; October 26, 2026
Genmab A/S (Nasdaq: GMAB) today announced updated results from a Phase 2 trial evaluating petosemtamab, an investigational IgG1-bispecific antibody targeting the epidermal growth factor receptor (EGFR) and leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5), in combination with pembrolizumab for first-line (1L) treatment of recurrent/metastatic PD-L1+ head and neck squamous cell carcinoma (r/m HNSCC). In the 1L combination arm, treatment with petosemtamab plus pembrolizumab achieved a median overall survival (OS) of 28.2 months, associated with an overall response rate (ORR) of 63% and median progression free survival (mPFS) of 9.0 months in efficacy-evaluable patients (n=43), including a complete response (CR) rate of 19%. The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2026, held in Madrid, Spain.
“For patients with recurrent or metastatic head and neck squamous cell carcinoma, there is an ongoing need for new treatment approaches that may help expand options beyond currently available regimens,” said Amaury Daste, M.D., Medical Oncologist, Hospital Center University de Bordeaux, France, and study investigator. “The median overall survival of 28 months observed with petosemtamab plus pembrolizumab in this trial, along with a manageable safety profile, are impressive. It is also particularly noteworthy that responses were observed across patient subgroups and continued to be maintained at the time of analysis, an important consideration for patients facing a disease where durable disease control remains a critical treatment goal.”
As of May 15, 2026, median duration of follow-up was 25.5 months; clinical activity was observed across combined positive PD L-1 expression levels and p16 subgroups. With more mature follow-up, the median OS was reached (12-month OS rate, 79%), with an ORR of 63%. Median duration of response (mDOR) was not reached, with an estimated 55% of responders maintaining a response at 24 months. Median PFS was 9.0 months (95% CI, 5.2–12.9; 12-month PFS rate, 40%).
The most common treatment-emergent adverse events (TEAEs) (all grade/Grade 3-4) were asthenia (51%/7%), acneiform dermatitis (51%/7%), and rash (49%/2%). Infusion-related reactions occurred in 38% of patients (7% Grade 3-4), and all resolved. No Grade 5 events nor treatment-related deaths were reported.
"These findings strengthen our confidence in petosemtamab’s potential to make a meaningful difference in first-line head and neck cancer,” said Tahamtan Ahmadi, M.D., Ph.D., Executive Vice President and Chief Medical Officer, Head of Experimental Medicines, Genmab. “Seeing responses across both HPV-positive and HPV-negative disease reinforces our ambition to reach a broad patient population and our commitment to advancing the petosemtamab clinical development program.”
Petosemtamab has the only triple mechanism of action that uniquely targets the LGR5+ stem-like cancer cells that drive tumor recurrence and metastases in epithelial cancers. In addition to this ongoing Phase 1/2 trial ( NCT03526835), the petosemtamab clinical program includes four Phase 3 LiGeR trials: in 1L PD-L1+ recurrent or metastatic head and neck squamous cell carcinoma (r/m HNSCC) (LiGeR-HN1; NCT06525220); in 2L/3L r/m HNSCC (LiGeR-HN2; NCT06496178), in 1L RAS/BRAF wild-type, left-sided unresectable or metastatic CRC (LiGeR-CRC1; NCT07702032); and in 2L RAS/BRAF wild-type recurrent, unresectable, or metastatic CRC (LiGeR-CRC2; NCT07775287).
On Wednesday, October 28 at 5:00 p.m. CET/12:00 p.m. EDT, Genmab will host an investor update. To register, visit genmab.com/events-presentations.
About the Phase 2 Petosemtamab Trial (NCT03526835)
The Phase 2 trial ( NCT03526835) is an ongoing, open-label, multicenter study evaluating petosemtamab as monotherapy and in combination with pembrolizumab across multiple solid tumors, including head and neck squamous cell carcinoma. In the first-line combination arm, 45 patients were treated with 1500 mg of petosemtamab every two weeks plus 400 mg of pembrolizumab every six weeks until disease progression or unacceptable toxicity. The trial includes a first-line combination cohort evaluating petosemtamab plus pembrolizumab, as well as monotherapy cohorts across later lines of therapy. Primary endpoints include objective response rate (ORR) and safety.
About Head and Neck Squamous Cell Carcinoma (HNSCC)
Head and Neck Squamous Cell Carcinoma (HNSCC) is a group of biologically similar cancers that arise from the tissue lining the surfaces of the oral cavity, pharynx and larynx and represent more than 90% of all head and neck cancers. i It is the seventh most common cancer globally. ii Risk for HNSCC is approximately two to four times higher in men than women. iii Treatment options vary depending on individual factors, including the location of the tumor, stage of the tumor, and a person’s overall health. iii Despite current treatment options, there remains a high patient need for additional therapies, as approximately 50% of patients with locally advanced HNSCC will experience disease recurrence following initial treatment. Recurrent or metastatic HNSCC is associated with a median overall survival of approximately 10-12 months. iv
About Petosemtamab (GEN1158)
Petosemtamab is an investigational human IgG1-based bispecific antibody targeting the EGFR and the LGR5 and designed to support multiple anti-tumor mechanisms. It inhibits EGFR-mediated signaling by engaging a unique site on the receptor to prevent ligand binding. In addition, petosemtamab triggers EGFR degradation in cancer stem-like cells expressing both EGFR and LGR5. Petosemtamab is also engineered to enhance innate immune-mediated activity through interactions with macrophages and natural killer cells. It is currently being investigated in head and neck squamous cell carcinoma (HNSCC) and other solid tumors, including colorectal cancer (CRC). Please visit https://clinicaltrials.gov/ for more information.
About Genmab
Genmab is an international biotechnology company dedicated to improving the lives of people with cancer and other serious diseases through innovative antibody medicines. For over 25 years, its passionate, innovative and collaborative team has advanced a broad range of antibody-based therapeutic formats, including bispecific antibodies, antibody drug conjugate (ADCs), immune-modulating antibodies and other next-generation modalities. Genmab’s science powers eight approved antibody medicines, and the company is advancing a strong late-stage clinical pipeline, including wholly owned programs, with the goal of delivering transformative medicines to patients.
Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com or follow us on LinkedIn, X, Facebook and Instagram.
Contact:
David Freundel, Senior Director, Global Communications & Corporate Affairs
T: +1 609 613 0504; E: dafr@genmab.com
Andrew Carlsen, Vice President, Head of Investor Relations
T: +45 3377 9558; E: acn@genmab.com
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i Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. “Head and neck squamous cell carcinoma.” Nat Rev Dis Primers, 2020 Nov 26;6(1):92. doi: 10.1038/s41572-020-00224-3. Erratum in: Nat Rev Dis Primers. 2023 Jan 19;9(1):4. doi: 10.1038/s41572-023-00418-5. PMID: 33243986; PMCID: PMC7944998.
ii Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A. “Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma.” Med Sci (Basel), 2023 Jun 13;11(2):42. doi: 10.3390/medsci11020042. PMID: 37367741; PMCID: PMC10304137.
iii Cancer Research Institute. “Head and Neck Cancer a Promising Treatment?” Accessed June 4, 2026. https://www.cancerresearch.org/immunotherapy-by-cancer-type/head-and-neck-cancer.
iv Ionna F, Bossi P, Guida A, Alberti A, Muto P, Salzano G, Ottaiano A, Maglitto F, Leopardo D, De Felice M, Longo F, Tafuto S, Della Vittoria Scarpati G, Perri F. “Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: A Big and Intriguing Challenge Which May Be Resolved by Integrated Treatments Combining Locoregional and Systemic Therapies.” Cancers (Basel), 2021 May 14;13(10):2371. doi: 10.3390/cancers13102371. PMID: 34069092; PMCID: PMC8155962.
Media Release no. 15
CVR no. 2102 3884
LEI Code 529900MTJPDPE4MHJ122
Genmab A/S
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