Telaglenastat falls short in kidney cancer

January 4, 2021
Jason M. Broderick

Combining telaglenastat with cabozantinib did not improve outcomes versus cabozantinib alone in a phase 2 trial.

Adding the glutaminase inhibitor telaglenastat to cabozantinib (Cabometyx) did not improve progression-free survival (PFS) in patients with advanced or metastatic renal cell carcinoma (RCC), according to topline findings from the phase 2 CANTATA trial.1

The median PFS was 9.2 months in patients receiving telaglenastat plus cabozantinib, compared with 9.3 months among patients treated with telaglenastat plus placebo (hazard ratio, 0.94; P = .65).

“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, the developer of telaglenastat, stated in a press release.

“Based on the strong scientific rationale for telaglenastat in KEAP1/NRF2 mutant non–small cell lung cancer patients, and the safety profile observed in CANTATA, we remain dedicated to advancing our randomized KEAPSAKE trial.”

The double-blind, global phase 2 CANTATA trial (NCT03428217) included 444 adult patients with advanced or metastatic RCC who had received 1 or 2 prior lines of systemic therapy. All patients had received at least 1 VEGF inhibitor or combination treatment with nivolumab (Opdivo) and ipilimumab (Yervoy). Patients had to have a Karnofsky Performance Score of 70% or higher.2

Patients were not eligible to enroll if they had received prior cabozantinib or another MET inhibitor, or if they had untreated or active brain metastases or central nervous system cancer.

The study randomized patients to telaglenastat or placebo orally twice daily, plus cabozantinib orally once daily. The primary end point was PFS.

In the press release, Calithera reported that it plans to present the complete results from the CANTATA trial at an upcoming medical conference.

Previously reported data had shown promise for telaglenastat in RCC. For example, findings from the phase 2 ENTRATA study presented at the 2019 ESMO Congress showed adding telaglenastat to everolimus (Afinitor) extended PFS compared with everolimus alone in patients with heavily pretreated advanced RCC.3

In the double-blind, randomized phase 2 ENTRATA trial, the median PFS for the telaglenastat plus everolimus cohort was 3.8 months compared to 1.9 months in the placebo plus everolimus group (HR, 0.64; one-sided P = .079). These results were promising to the study investigators, as the PFS improvement met the prespecified threshold for achieving the primary end point (one-sided P value of ≤0.2).

References

1. Calithera Biosciences Reports CANTATA Study of Telaglenastat in Renal Cell Carcinoma Did Not Achieve Primary Endpoint. Published January 4, 2021. https://bit.ly/3oiDZfN. Accessed January 4, 2021.

2. NIH ClinicalTrials.gov. CANTATA: CB-839 With Cabozantinib vs. Cabozantinib With Placebo in Patients With Metastatic Renal Cell Carcinoma (CANTATA). Updated October 14, 2019. https://clinicaltrials.gov/ct2/show/NCT03428217. Accessed January 4, 2021.

3. Motzer RJ, Lee C-H, Emamekhoo H, et al. ENTRATA: Randomized, double-blind, phase 2 study of telaglenastat (tela; CB-839) + everolimus (E) vs. placebo (pbo) + E in patients (pts) with advanced/metastatic renal cell carcinoma (mRCC). Presented at: 2019 ESMO Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA54.