JAVELIN head and neck 100: A phase 3 trial of avelumab in combination with chemoradiotherapy (CRT) vs CRT for 1st-line treatment of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).

TPS6093 Background: Cisplatin + radiotherapy is a standard-of-care treatment for patients (pts) with LA SCCHN. Combining avelumab (fully human IgG1 anti–PD-L1 antibody) and CRT may synergistically activate multiple immune-mediated mechanisms to effect a robust and durable antitumor response and improve long-term disease control. Methods: JAVELIN Head and Neck 100 (NCT02952586) is a global, multicenter, randomized, double-blind, phase 3 trial of avelumab + cisplatin-based CRT vs placebo + CRT as 1st-line treatment for pts with LA SCCHN. The primary objective is to demonstrate superiority of avelumab + CRT in prolonging progression-free survival (PFS) vs CRT alone. Eligible pts have LA SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx; HPV− or non-oropharyngeal HPV+ disease of stage III, IVa, or IVb; or HPV+ oropharyngeal disease T4, N2c, or N3. Pts must be candidates for cisplatin-based CRT. Other eligibility criteria include ECOG PS ≤1 and no prior systemic treatment for advanced disease. Approximately 640 pts will be randomized 1:1 to receive avelumab 10 mg/kg (1-hour IV) + CRT (intensity-modulated RT [70 Gy/35 fractions] + cisplatin 100 mg/m2 [x3]) or placebo + CRT. There will be 3 treatment phases: lead-in (single dose of avelumab or placebo), CRT (concurrent avelumab or placebo + CRT for 7 weeks), and maintenance (avelumab or placebo Q2W for 12 months). The rationale for this design is to induce an immune response during lead-in and CRT phases, followed by maintenance treatment to prolong and support immune memory development. The primary endpoint is PFS per modified RECIST v1.1. Secondary efficacy endpoints include overall survival, objective response, locoregional failure, distant metastatic failure, and duration of response. Other endpoints include safety, pharmacokinetics, immunogenicity, pt-reported outcomes, and biomarker assessments. Treatment will continue for 12 months following initiation of the maintenance phase or until progressive disease, unacceptable toxicity, or any other protocol-defined criterion for withdrawal occurs. Enrollment in this phase 3 trial began in November 2016. Clinical trial information: NCT02952586.