Balstilimab Alone Or In Combination With Zalifrelimab As Second-Line Treatment For Patients With Previously Treated Recurrent/Metastatic Cervical Cancer (R/M Cc): A Randomized, Placebo-Controlled Phase Ii Trial (Rapids/Gog-3028)

For patients with R/M CC, treatment options beyond platinum-based chemotherapy are limited and typically administered without expectation of cure. Targeting the PD-1/PD-L1 immune checkpoint pathway has provided an important advance in the management of advanced CC, however opportunities remain to improve on current outcomes. Amongst these, dual blockade of the PD-1/PD-L1 and CTLA-4 immune checkpoints represents a rational therapeutic strategy, given this approach has been shown to be highly effective in multiple tumor types. Balstilimab (anti-PD-1) and zalifrelimab (anti-CTLA-4) are two new checkpoint inhibitors that have emerged as promising investigational agents for patients with R/M CC who have progressed after first-line, platinum-based chemotherapy. RaPiDS is a randomized, blinded, two-arm phase II trial evaluating the efficacy and safety of balstilimab administered as either monotherapy or in combination with zalifrelimab. Planned enrollment is 210 pts with a confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, that has relapsed after a first-line, platinum-based regimen for advanced (recurrent, unresectable, or metastatic) disease. Patients are randomized 1:1 into two treatment arms to receive balstilimab with placebo as monotherapy (Arm 1) or with zalifrelimab as combination therapy (Arm 2). Treatment is administered for up to 24 months or until disease progression, unacceptable toxicity, or other criteria for trial withdrawal occur. The primary endpoint is objective response rate determined by an Independent Radiology Review Committee according to RECIST v1.1 and key secondary endpoints include safety, duration of response, progression-free survival, overall survival, and quality of life outcomes. Recruitment is ongoing with 65 patients enrolled as of May 1, 2021 at centers across the United States. NCT03894215. Agenus Inc. Agenus Inc.