A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Head and Neck Cancer (LiGeR - HN1)

Eligibility 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% or ≥ institutional normal limit, whichever is higher, 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
• 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 petosemtomab 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)