Phase 2 CANTATA Study of Telaglenastat Fails to Meet Primary End Point for Advanced Clear Cell RCC

Topline results from the CANTATA clinical study (NCT03428217) that were announced by Calithera Biosciences revealed that compared with cabozantinib (Cabometyx) and placebo, combination treatment with telaglenastat (CB-839) versus placebo added to therapy with cabozantinib (Cabometyx) failed to meet the primary end point of improved progression-free survival (PFS) in patients with advanced or metastatic clear cell renal cell carcinoma (RCC).¹

Telaglenastat was designed to be a selective, reversible, and orally bioavailable inhibitor of the enzyme glutaminase.² Glutaminase which transforms glutamine to glutamate, has been identified as a pivotal biologic component in the use of glutamine by cancer cells.

The global, randomized, double-blind phase 2 trial is designed to assess the efficacy and safety of telaglenastat in combination with cabozantinib versus placebo with cabozantinib in patients with advanced or metastatic RCC who have been treated with 1 or 2 prior lines of systemic therapy, including at least 1 VEGF targeted therapy or the combination of nivolumab (Opdivo) and ipilimumab (Yervoy).

Patients randomized to the experimental arm are administered telaglenastat orally twice daily versus oral placebo twice daily in the comparator arm; all patients receive cabozantinib orally once daily. Treatment will continue until unacceptable toxicity, disease progression, or study conclusion.

In total, 444 patients from multiple centers globally were enrolled in the CANTATA trial. The primary end point of the study is PFS per blinded independent review.

The hazard ratio for the PFS comparison of the experimental versus control arm was 0.94 (P = .65). The median PFS was 9.2 months among patients treated with telaglenastat and cabozantinib, which was similar to the 9.3 months observed with cabozantinib and placebo. Importantly, treatment with prior PD-1/L1 therapy was noted in 62% of the trial population, and these were well balanced in the 2 arms.

Regarding safety, the frequency and severity of adverse events in the patients treated with telaglenastat were comparable to those observed with cabozantinib alone.

“We are disappointed that the CANTATA trial did not achieve its primary end point, particularly on behalf of the people living with advanced RCC, many of whom could benefit from additional treatment options with novel mechanisms of action to address this difficult-to-treat disease,” Susan Molineaux, PhD, president and chief executive officer of Calithera, said in a press release. “Based on the strong scientific rationale for telaglenastat in [patients with] KEAP1/NRF2-mutant non–small cell lung cancer [NSCLC], and the safety profile observed in CANTATA, we remain dedicated to advancing our randomized KEAPSAKE trial.”

Moving forward, Calithera indicated it will focus its resources on the ongoing KEAPSAKE trial (NCT04265534), which is investigating telaglenastat in KEAP1/NFR2-mutant nonsquamous NSCLC, as well as other pipeline programs .

References:

1. Calithera Biosciences reports CANTATA study of telaglenastat in renal cell carcinoma did not achieve primary endpoint. News release. Calithera Biosciences, Inc. Published January 4, 2021. Accessed January 4, 2021. https://www.globenewswire.com/fr/news-release/2021/01/04/2152519/0/en/Calithera-Biosciences-Reports-CANTATA-Study-of-Telaglenastat-in-Renal-Cell-Carcinoma-Did-Not-Achieve-Primary-Endpoint.html

2. CANTATA trial. Cantata trial website. Published 2018. Accessed January 4, 2021. https://www.cantatatrial.com/