LBA54ENTRATA: Randomized, double-blind, phase II study of telaglenastat (tela; CB-839) + everolimus (E) vs placebo (pbo) + E in patients (pts) with advanced/metastatic renal cell carcinoma (mRCC)

Abstract Background Altered glucose and glutamine (gln) metabolism is a hallmark of RCC. Glutaminase (GLS) is a key enzyme in gln metabolism and drives proliferation of RCC cells when overexpressed. Tela, a novel, first-in-clinic, selective GLS inhibitor, blocks critical gln-dependent pathways and synergizes preclinically with signal transduction inhibitors (eg, E). In a phase I study in mRCC, telaE was well tolerated and had encouraging clinical activity. We present here results of a randomized phase II study of telaE vs pboE in 3L+ mRCC (NCT03163667). Methods Eligible pts had ≥2 prior lines of systemic therapy for mRCC, including ≥1 VEGFR-targeted tyrosine kinase inhibitor (TKI), KPS ≥70%, and measurable disease (RECIST 1.1). Pts were stratified by prior lines of TKI and MSKCC risk and randomized 2:1 to receive tela (800 mg PO BID) or pbo, plus E (10 mg PO QD), until disease progression/unacceptable toxicity. Primary endpoint is investigator-assessed progression-free survival (PFS) (RECIST 1.1; 1-sided alpha