Cantata: A Randomized Phase 2 Study Of Cb-839 In Combination With Cabozantinib Vs. Placebo With Cabozantinib In Patients With Advanced/Metastatic Renal Cell Carcinoma.

TPS4601Background: Glutamine utilization is a metabolic pathway upregulated in renal cell carcinoma (RCC) and important for RCC tumor cell proliferation and survival. CB-839 is a first-in-class, potent, oral inhibitor of the mitochondrial enzyme glutaminase (GLS) that controls a critical step in tumor cell utilization of glutamine. In preclinical RCC models, CB-839 demonstrated synergistic anti-tumor activity when combined with cabozantinib, a VEGFR/MET inhibitor. A phase 1 study cohort of CB-839 plus cabozantinib as 2L+ therapy showed encouraging safety and efficacy results, with 40% overall response rate (ORR; RECIST v1.1) and 100% disease control rate in patients with clear cell advanced/metastatic RCC (mRCC). These findings prompted the initiation of a randomized phase 2 study comparing CB-839 plus cabozantinib vs. placebo plus cabozantinib in patients with clear cell mRCC. Methods: This international, randomized, double-blind, placebo-controlled, multi-center study (NCT03428217) will enroll ~300 pati...