Phase 3 trial — LiGeR-HN1 (NCT06525220), both primary endpoints met at first interim analysis (announced 2026-10-28) Two U.S. FDA Breakthrough Therapy designations Not yet approved — regulatory discussions planned
New head and neck cancer drug candidate petosemtamab has produced encouraging phase 3 results. On October 28, 2026, Danish drugmaker Genmab announced that in first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma, petosemtamab plus the immunotherapy pembrolizumab (Keytruda) cut the risk of death by 50% compared with pembrolizumab alone. Tumor shrinkage was also clearly more frequent with the combination.
Petosemtamab is a bispecific antibody that hits two targets
Petosemtamab is a bispecific antibody: one molecule that binds two targets. The first is EGFR, which is abundant on head and neck cancer cells. The second is LGR5, found on cells that behave like cancer stem cells. It was developed by the Dutch biotech Merus, and Genmab continued development after acquiring Merus in 2025.
According to the company, the drug works in three ways. It blocks EGFR signaling so cancer cells stop receiving growth signals. In cells carrying both targets, it helps pull EGFR inside the cell to be broken down. And because the sugar on the antibody's tail is reduced (low-fucose), immune cells such as NK cells attack cancer cells more effectively. Adding pembrolizumab, which releases the immune system's brakes, creates a chemotherapy-free two-drug treatment.
Who it is for: first-line PD-L1-positive recurrent or metastatic disease
LiGeR-HN1 enrolled patients with recurrent or metastatic head and neck squamous cell carcinoma that could not be cured with surgery or radiotherapy. This cancer arises in the mouth, pharynx and larynx and accounts for more than 90% of head and neck cancers. Key criteria were:
- Adults with no prior systemic therapy for recurrent or metastatic disease (first-line)
- PD-L1 combined positive score (CPS) of 1 or higher
- No prior PD-1/PD-L1 immunotherapy or EGFR antibody (cetuximab given with radiotherapy was allowed if recurrence came more than one year later)
- Performance status (ECOG) 0 or 1
The benefit was reported regardless of human papillomavirus (HPV) status. Current standard first-line options include pembrolizumab alone, approved in the U.S. in 2019, or pembrolizumab with chemotherapy. Company materials describe median survival in recurrent or metastatic disease as about 10 to 12 months, so expectations for new treatment are high.
Phase 3 and phase 2 results: risk of death halved, phase 2 median survival 28.2 months
LiGeR-HN1 is a multinational, randomized, open-label phase 3 trial. Patients were assigned 1:1 to the combination or pembrolizumab alone, with overall survival and objective response rate as dual primary endpoints. An independent data monitoring committee found both endpoints met at the first interim analysis.
| Measure | Result |
|---|---|
| Phase 3 overall survival hazard ratio (HR) | 0.50 (95% CI 0.37–0.67, p<0.0001) — 50% lower risk of death |
| Phase 3 objective response odds ratio | 3.17 (95% CI 2.06–4.89, p<0.0001) |
| Phase 2 median overall survival | 28.2 months (1-year survival 79%) |
| Phase 2 response rate · complete response | 63% · 19% |
| Phase 2 median progression-free survival | 9.0 months (1-year 40%) |
| Phase 2 durability | About 55% of responders still responding at 24 months |
Sources: Genmab phase 3 announcement (2026-10-28) and phase 2 update (ESMO 2026, 2026-10-26). Phase 2: 43 evaluable first-line patients, median follow-up 25.5 months. A hazard ratio below 1 favors the combination.
Exact phase 3 response rates and survival times have not yet been released; full results will be presented at an upcoming medical meeting. The phase 2 data presented two days earlier at ESMO 2026 give a preview. Of 43 patients receiving the same combination, 63% had tumor shrinkage and 19% reached a complete response, with no visible tumor on imaging. Median survival was 28.2 months, more than two years. Head and neck cancer expert Dr. Everett Vokes called it the first positive phase 3 study in this patient population in several years.
Side effects and how they are managed: skin symptoms and infusion reactions
In phase 3 the combination was generally well tolerated, with no new safety signals beyond those known for each drug. In phase 2 the most common side effects were fatigue/weakness (51%, grade 3–4 in 7%), acne-like dermatitis (51%, grade 3–4 in 7%) and rash (49%, grade 3–4 in 2%). These skin effects are typical of EGFR-blocking drugs and are managed with moisturizers, sun protection and, when needed, topical or oral medicines.
Infusion-related reactions occurred in 38% (grade 3–4 in 7%), and all resolved. Pre-medication and adjusting the infusion rate help prevent them. There were no treatment-related deaths in phase 2. The phase 2 dose was petosemtamab 1,500 mg every two weeks plus pembrolizumab 400 mg every six weeks, both given intravenously.
Where it is available: preparing for regulatory filing
- United States: The FDA has granted Breakthrough Therapy designation to this combination (first-line, PD-L1-positive) and to petosemtamab alone (after platinum chemotherapy and immunotherapy). Genmab plans to discuss the results with regulators worldwide.
- Clinical trials: The phase 3 LiGeR-HN2 trial (NCT06496178) in second and third line, and the colorectal cancer phase 3 trials LiGeR-CRC1 and CRC2, are ongoing. Participating hospitals can be found on ClinicalTrials.gov by trial number.
- Japan and Europe: As of the date checked, no filing timeline has been announced. Updates by country can be followed through Genmab's official announcements.
For an overview of head and neck cancer care, see Head and neck cancer information. For an option already approved in Japan, see head and neck photoimmunotherapy results and photoimmunotherapy combined with immunotherapy.
Points to check and questions for your doctor
- What is the PD-L1 CPS of my cancer? Do I need a new test?
- Could I join a petosemtamab clinical trial (LiGeR-HN1 or HN2)?
- How does this compare with the first-line options available to me now?
- How should I prepare for skin side effects, with medicines and daily care?
- Does my HPV test result affect the choice of treatment?
Frequently asked questions
What is the new head and neck cancer drug petosemtamab?
It is a bispecific antibody that binds both EGFR and LGR5. It blocks cancer growth signals and helps immune cells such as NK cells attack cancer cells. It was developed by Merus and is now developed by Genmab.
What were the LiGeR-HN1 phase 3 results?
At the first interim analysis, the risk of death was 50% lower than with pembrolizumab alone (hazard ratio 0.50), and the response odds ratio was 3.17. The benefit was seen regardless of HPV status; detailed figures will be presented at a future meeting.
What are the side effects of petosemtamab?
In phase 2, fatigue, acne-like dermatitis and rash each occurred in about half of patients, mostly grade 1–2. Infusion reactions occurred in 38%, and all resolved. Skin care and pre-medication help manage them.
Can I receive petosemtamab now?
As of the date checked (2026-10-31), it is not approved in any country and is available through clinical trials. With FDA Breakthrough Therapy designation, its review could move quickly.
Related: FDA approves talazoparib for prostate cancer · Types of immune cell therapy compared · All articles by cancer type
Sources
- Genmab — Statistically significant improvement in overall survival and objective response with petosemtamab combination at first interim analysis (LiGeR-HN1, 2026-10-28)
ir.genmab.com
Checked: 2026-10-31 - Genmab — Updated phase 2 data: more than two-year median overall survival with petosemtamab plus pembrolizumab (ESMO 2026, 2026-10-26)
via.ritzau.dk
Checked: 2026-10-31 - Targeted Oncology — Petosemtamab plus pembrolizumab improves OS in PD-L1+ HNSCC (2026-10-28)
targetedonc.com
Checked: 2026-10-31 - OncLive — Petosemtamab plus pembrolizumab hits phase 3 OS, ORR primary end points in PD-L1-positive R/M HNSCC (2026-10-28)
onclive.com
Checked: 2026-10-31 - BioPharm International — Petosemtamab plus pembrolizumab cuts risk of death by 50% in phase 3 head and neck cancer trial (2026-10-28)
biopharminternational.com
Checked: 2026-10-31 - ClinicalTrials.gov — NCT06525220: LiGeR-HN1
clinicaltrials.gov/study/NCT06525220
Checked: 2026-10-31
Written by the FTH editorial team. Sources checked 2026-10-31 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
