GOG 3016/ENGOT-cx9: An open-label, multi-national, randomized, phase 3 trial of cemiplimab, an anti-PD-1, versus investigator's choice (IC) chemotherapy in ≥2 line recurrent or metastatic cervical cancer.

Abstract

Background: Patients with recurrent and metastatic cervical carcinoma experience modest survival benefit with first‐line platinum‐based chemotherapy with or without bevacizumab. Those with platinum‐refractory disease have a median survival of only 7 months. Cemiplimab, a human monoclonal anti‐PD‐1, has exhibited antitumor activity and an acceptable safety profile in a phase 1 trial of solid tumors including recurrent cervical cancer. Methods: GOG 3016/ENGOT‐cx9 is an open‐label, randomized (1:1), phase 3 trial of cemiplimab versus IC chemotherapy in women ≥18 years with platinum‐refractory recurrent and/or metastatic cervical cancer that has progressed within 6 months of the last dose of platinum‐containing chemotherapy (NCT03257267). Patients will be stratified for the primary efficacy analysis by histology and geographic region. Patients will receive cemiplimab every 3 weeks (Q3W) or IC chemotherapy, ie, pemetrexed 500 mg/m Q3W; topotecan 1 mg/m daily x5 days, every 21 days; irinotecan 100 mg/m days 1, 8, 15, and 22, followed by 2 weeks rest, for a 42‐day (6‐week cycle); gemcitabine 1000 mg/m days 1 and 8, every 21 days; or vinorelbine 30 mg/m days 1 and 8, every 21 days. Treatments will be given IV for up to 96 weeks. The primary objective is overall survival (OS). Key secondary objectives include the assessment of overall response, progression‐free survival, and the frequency and severity of adverse events. Stratification factors include prior bevacizumab, histology, and ECOG status. Assuming duration of study enrollment and follow‐up of 20 months and 12 months, respectively, we calculated we would need to enroll approximately 436 patients, with 330 deaths expected, to provide the study with 90% power to detect a reduction in the risk of death of at least 20% with cemiplimab, with the 1‐sided type 1 error rate limited to 2.5%. An independent data monitoring committee (IDMC) will monitor the data during the study conduct.