ROCK Trial (NCCH1709): Nivolumab monotherapy in Rare cancer patients with mismatch repair deficiency biomarker: phase II

Abstract

Background: Mismatch repair deficiency (dMMR) / microsatellite instability-high (MSI-H) in cells lead to neoplastic development and progression, an important feature in Lynch syndrome. dMMR/MSI-H is a positive predictive marker for immune checkpoint inhibitors. Nivolumab is a PD-1 inhibitor, approved in the US for pts with dMMR/MSI-H colorectal cancers. Other than colorectal cancers, a subset of rare cancers also share this characteristic. Methods: This is a phase 2, open-label, single arm study designed to investigate the efficacy and safety of nivolumab monotherapy in patients with advanced rare tumors with dMMR/MSI-H. This study is conducted as part of the MASTER KEY Project, which is a basket/umbrella trial including a registry study for rare cancers (UMIN000027552). dMMR was identified by a negative immunohistochemical staining of one of the following: MLH1, MSH2, MSH6, PMS2. Rare cancer was defined as annual incidence < 6 / 100,000 population. Other main inclusion criteria were: age ≥ 16, ECOG-PS of 0-1, unresectable lesion and have completed standard treatment, adequate organ function. Patients will receive intravenous nivolumab monotherapy of 240 mg every 2 weeks until disease progression, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, or death. Primary endpoint is response rate (central assessment), and secondary endpoints include progression free survival, overall survival, stable disease rate and toxicity. The trial will utilize a Bayesian hierarchical model enrolling 5 to 15 patients depending on the ongoing results as an adaptive design. Participating sites are National Cancer Center and Kyoto University Hospital, and will be expanding shortly. Clinical Trial Information: JMA-IIA00344