A Phase 2/3, Randomized, Open-Label Study of Bempegaldesleukin Plus Pembrolizumab vs. Pembrolizumab Alone in First-Line Treatment of Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma with PD-L1-Expressing Tumors (PROPEL-36)

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<h3>Purpose/Objective(s)</h3> Head and neck squamous cell carcinoma (HNSCC) represents the 8th most common cancer worldwide.¹ However, survival rates remain low at ≈50%, despite standard first-line treatment with the immune checkpoint inhibitor (ICI) pembrolizumab (PEMBRO) ± chemotherapy.² Recombinant interleukin-2 (IL-2) is associated with improved overall survival (OS) in HNSCC patients.³ Research has shown that high levels of tumor-infiltrating lymphocytes are prognostic of disease-free survival in this patient population. Bempegaldesleukin (BEMPEG; NKTR-214), a first-in-class immunostimulatory IL-2 cytokine prodrug, is engineered to deliver a controlled, sustained, and preferential signal to the clinically validated IL-2 pathway to selectively stimulate antitumor responses. Earlier studies of BEMPEG in combination with ICIs evaluated in patients with immune-sensitive cancers have shown the potential to increase and deepen treatment responses vs historical rates for ICIs alone.⁴ Here, we present the design of the PROPEL-36 study (NCT04969861) that evaluates BEMPEG + PEMBRO vs PEMBRO alone in patients with previously untreated metastatic or recurrent programmed death ligand-1 (PD-L1)-positive HNSCC (combined positive score ≥1). <h3>Materials/Methods</h3> This phase 2/3, multicenter study is enrolling ≈500 patients with cancer of the oropharynx, oral cavity, hypopharynx, or larynx (excluding nasopharyngeal tumors) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Randomization will be stratified by disease status, PD-L1 expression, and human papillomavirus status. Patients are treated with BEMPEG and/or PEMBRO every 3 weeks for up to 35 cycles (≈2 years). The primary endpoints are OS and objective response rate. Secondary endpoints include progression-free survival, time to deterioration in global health status/quality of life, pain, and swallowing, change in quality of life, and safety. This study is now enrolling. <h3>Results</h3> TBD <h3>Conclusion</h3> TBD