Glutaminase inhibitor telaglenastat does not improve survival mRCC

First results of the phase 3 CANTATA trial showed no survival benefit of treatment with the glutaminase inhibitor telaglenastat plus cabozantinib versus cabozantinib alone in patients with previously treated metastatic renal cell cancer (mRCC).

Renal cell cancer is a highly metabolic tumour with high expression of glutaminase, a key enzyme in glutamine metabolism. Telaglenastat is a potent glutaminase inhibitor showing promising anti-tumour effect in heavily pretreated mRCC patients when combined with everolimus or cabozantinib [1,2]. The phase 3 CANTATA trial (NCT03428217) evaluated the efficacy and safety of the combination telaglenastat plus cabozantinib in patients with previously treated mRCC.

Eligible patients had 1 or 2 prior lines of systemic therapy for mRCC, including at least 1 anti-angiogenic therapy or nivolumab/ipilimumab. A total of 444 patients were enrolled and randomised to receive cabozantinib (60 mg once daily) with either telaglenastat (800 mg twice daily) or placebo, until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival by BICR. Dr Nizar Tannir (Houston University, TX, USA) presented the first results [3].

Median progression-free survival was 9.2 months for cabozantinib/telaglenastat versus 9.3 months for cabozantinib/placebo (HR 0.94; 95% CI 0.74–1.21; P=0.65). The overall response rate was 31% with cabozantinib/telaglenastat versus 28% with cabozantinib/placebo. Overall survival was not mature at data cut-off. In a prespecified subgroup analysis in patients with prior immune checkpoint inhibition, median progression-free survival was numerically longer in the telaglenastat arm than in the placebo arm (11.1 versus 9.2 month, respectively; HR 0.77; 95% CI 0.56–1.06). Rates of adverse events were similar between arms.

1. Motzer R, et al. Abstract 811, ESMO 2019 Annual Meeting, 27 Sept–1 Oct, Barcelona, Spain.
2. Meric-Bernstam F, et al. Abstract 549, ASCO-GU 2019, 17–19 Feb, San Fransico, USA.
3. Tannir NM, 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. Abstract 4501, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August 202117 August 2021