Telaglenastat plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase II ENTRATA Trial
Purpose: Glutaminase is really a key enzyme, which assists elevated dependency of tumors on glutamine-dependent biosynthesis of metabolic intermediates. Dual targeting of glucose and glutamine metabolic process through the mTOR inhibitor everolimus as well as the dental glutaminase inhibitor telaglenastat demonstrated preclinical synergistic anticancer effects, which converted to encouraging safety and effectiveness findings inside a phase I trial of 2L kidney cell carcinoma (RCC). This research evaluated telaglenastat plus everolimus (TelaE) versus placebo plus everolimus (PboE) in patients with advanced/metastatic RCC (mRCC) within the 3L setting (NCT03163667).
Patients and techniques: Qualified patients with mRCC, formerly given a minimum of two prior lines of therapy [including =1 VEGFR-targeted tyrosine kinase inhibitor (TKI)] were randomized 2:1 to get E, plus Tela or Pbo, until disease progression or unacceptable toxicity. Primary endpoint was investigator-assessed progression-free survival (PFS one-sided a <0.2). Results: Sixty-nine patients were randomized (46 TelaE, 23 PboE). Patients had a median three prior lines of therapy, including TKIs (100%) and checkpoint inhibitors (88%). At median follow-up of 7.5 months, median PFS was 3.8 months for TelaE versus 1.9 months for PboE [HR, 0.64 95% confidence interval (CI), 0.34-1.20 one-sided P = 0.079]. One TelaE patient had a partial response and 26 had stable disease (SD). Eleven patients on PboE had SD. Treatment-emergent adverse events included fatigue, anemia, cough, dyspnea, elevated serum creatinine, and diarrhea grade 3 to 4 events occurred in 74% TelaE patients versus 61% PboE. Conclusions: TelaE was well tolerated and improved PFS versus PboE in patients with mRCC previously treated with TKIs and checkpoint inhibitors.