IMvoke010: Randomized phase III study of atezolizumab (atezo) as adjuvant monotherapy after definitive therapy of squamous cell carcinoma of the head and neck (SCCHN)

Abstract

Background: Locally advanced SCCHN is associated with a high risk for local recurrence and distant metastases. Treatment includes a combination of surgery, radiation therapy and chemotherapy to optimize the chances for long‐term disease control and improved survival. After definitive local therapy, patients (pts) are monitored for local recurrence and/or distant metastases as standard of care. No effective systemic adjuvant treatment has been identified. Atezo is an anti‐programmed death‐ligand 1 (PD‐L1) monoclonal antibody that prevents PD‐L1 from binding to its receptors PD‐1 and B7.1, thereby restoring anti‐tumor immunity. Efficacy results from a cohort of pts with recurrent/metastatic SCCHN in the Phase I PCD4989g study suggest that atezo offers a potential clinical benefit. The objective of IMvoke010 (NCT03452137) is to evaluate the efficacy and safety of adjuvant atezo in pts with locally advanced SCCHN who are at high risk for disease recurrence or progression following definitive curative therapy. Trial design: IMvoke010 is a global, double‐blind, placebo‐controlled, randomized Phase III trial enrolling pts who have completed definitive local/regional therapy for Stage III human papillomavirus (HPV)‐positive oropharyngeal carcinoma or Stage IVA or IVB HPV‐negative SCCHN involving the oral cavity, oropharynx, larynx or hypopharynx and are at high risk for disease recurrence or progression. Approximately 400 pts will be randomized 1:1 to receive placebo or atezo 1200 mg Q3W for up to a year (≤16 cycles) or until unacceptable toxicity, disease recurrence or progression. Pts with nasopharyngeal carcinoma, metastatic disease, or progressive disease during or at completion of definitive local therapy will be excluded. Stratification factors include HPV status, response to definitive local therapy and whether primary surgery was performed as part of definitive therapy. Primary endpoints are independent review facility‐assessed event‐free survival (EFS) and overall survival. Key secondary endpoints include investigator‐assessed EFS, safety, and patient reported outcomes. Exploratory biomarkers will also be assessed.