Using the investigational agent telaglenastat in combination with cabozantinib was no more efficacious than placebo plus cabozantinib in patients with metastatic renal cell carcinoma (mRCC) whose disease progressed on immune checkpoint inhibitor (ICI) or antiangiogenic therapies, according to data presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Telaglenastat is a first-in-class selective oral glutaminase inhibitor that blocks glutamine utilization and critical downstream pathways. Preclinical research showed that telaglenastat synergized with cabozantinib against RCC tumors. In a phase 1 study, the combination of telaglenastat plus cabozantinib showed encouraging safety and efficacy in heavily pretreated patients with mRCC.

In the CANTATA trial (ClinicalTrials.gov Identifier: NCT03428217), investigators randomly assigned 444 patients to receive telaglenastat plus cabozantinib (221 patients) or placebo plus cabozantinib (223 patients). Of these patients, 276 received prior ICI therapy, including 128 who received nivolumab plus ipilimumab. The median follow-up duration was 11.7 months.


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Median progression-free survival (PFS) was 9.2 months for the telaglenastat plus cabozantinib arm and 9.3 months for the placebo plus cabozantinib arm (hazard ratio [HR], 0.94; 95% CI, 0.74-1.21; stratified log-rank P =.65), according to Nizar M. Tannir, MD, FACP, of The University of Texas MD Anderson Cancer Center in Houston. Overall response rates were 31% and 28%, respectively.

In a prespecified subgroup analysis of patients who had received prior ICI therapy, median PFS was 11.1 months in the telaglenastat plus cabozantinib arm compared with 9.2 months in the placebo plus cabozantinib arm (unstratified HR, 0.77; 95% CI, 0.56-1.06). Overall survival was not mature at data cutoff, the investigators noted.

Adverse event (AE) rates were similar between treatment arms, with grade 3 or 4 AEs occurring in 71% of the telaglenastat plus cabozantinib arm and 79% in the placebo plus cabozantinib arm.

Disclosure: This research was supported by Calithera Biosciences, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Tannir NM, Agarwal N, Porta C, et al. CANTATA: Primary analysis of a global, randomized, placebo (Pbo)-controlled, double-blind trial of telaglenastat (CB-839) + cabozantinib versus Pbo + cabozantinib in advanced/metastatic renal cell carcinoma (mRCC) patients (pts) who progressed on immune checkpoint inhibitor (ICI) or anti-angiogenic therapies. J Clin Oncol. 2021;39:(suppl 15; abstr 4501). doi:10.1200/JCO.2021.39.15_suppl.4501

This article originally appeared on Cancer Therapy Advisor