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Evaluating a new treatment for head and neck cancer

A Phase 3 Randomized, Open-label Study to Evaluate the Efficacy and Safety of Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Recurrent or Metastatic PD-L1+ Head and Neck Squamous Cell Carcinoma

Phase 3 Interventional Merus B.V. · NCT06525220

This study is testing a new treatment combining petosemtamab and pembrolizumab to see if it helps people with advanced head and neck cancer more than pembrolizumab alone.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment700 (estimated)
Ages18 Years and up
SexAll
SponsorMerus B.V. Industry-sponsored
Drugs / interventionspembrolizumab, petosemtamab, radiation, prednisone, cetuximab
Locations202 sites (Mobile, Alabama and 201 other locations)
Trial IDNCT06525220 on ClinicalTrials.gov

What this trial studies

This Phase 3 randomized, open-label study aims to assess the efficacy and safety of petosemtamab combined with pembrolizumab compared to pembrolizumab alone in patients with recurrent or metastatic PD-L1+ head and neck squamous cell carcinoma (HNSCC). Eligible participants must have histologically confirmed HNSCC and have not received prior systemic therapy in the recurrent or metastatic setting. The study will involve measurable disease assessments and requires a new tumor biopsy or archival sample for evaluation.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with recurrent or metastatic PD-L1+ HNSCC who have not received prior systemic therapy.

Not a fit: Patients who have previously received systemic therapy for recurrent or metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective first-line option for patients with advanced head and neck cancer.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches in treating head and neck cancers, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Signed ICF before initiation of any study procedures
2. Age ≥ 18 years at signing of ICF
3. Histologically confirmed HNSCC with evidence of metastatic or locally recurrent disease not amenable to local therapy with curative intent.
4. The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
5. HNSCC patients eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD-L1, CPS ≥1.
6. HNSCC patients should not have had previous systemic therapy administered in the incurable recurrent or metastatic setting
7. A new tumor biopsy, unless the patient has an available archival tumor sample with sufficient material
8. Measurable disease per Investigator assessment as defined by RECIST v1.1 by radiologic methods
9. ECOG Performance Status (PS) of 0-1
10. Life expectancy ≥ 12 weeks, as per investigator assessment.
11. Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
12. Adequate organ function as defined per protocol.
13. HIV-positive patients are eligible only if the cluster of differentiation 4 (CD4+) count is ≥ 300/µl, viral load is undetectable, and the patient is currently receiving highly active antiretroviral therapy

Exclusion Criteria:

1. Central nervous system metastases that are untreated or already treated but symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 21 days prior to randomization
2. Known leptomeningeal involvement
3. Any systemic anticancer therapy or investigational drug within 4 weeks or 5 half-lives, whichever is shorter, before randomization
4. Requirement for immunosuppressive medication
5. Major surgery or radiotherapy within 3 weeks of randomization
6. Clinically significant toxicities related to prior anticancer therapies that have not returned to ≤ Grade 1 or baseline except for Grade ≤2- myalgia, neuropathy, alopecia, and any prior therapy related endocrinopathies
7. History of hypersensitivity reaction to any of the excipients of petosemtamab or pembrolizumab.
8. Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment; or history of myocardial infarction within 6 months prior to randomization
9. History of prior malignancies within the last 5 years, with the exception of excised local cancer
10. Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy
11. Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders
12. Patients with known infectious diseases as per protocol.
13. Pregnant or breastfeeding patients.
14. The patient has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy of prednisone \>10 mg/day or equivalent, or any other form of immunosuppressive therapy
15. The patient has an active autoimmune disease that has required systemic immune suppressive treatment in the past 2 years; replacement therapy is not considered immune suppressive treatment
16. The patient has had an allogeneic tissue/solid organ transplant.
17. Patient has a primary tumor site of nasopharynx, or sinonasal carcinoma (any histology)

Other protocol defined inclusion/exclusion criteria may apply.

Where this trial is running

Mobile, Alabama and 201 other locations

+152 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Head and Neck Squamous Cell CarcinomaHNSCCPD-L1+Head and Neck cancerPetosemtamabPembrolizumabLigerOral Cavity
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.