Telaglenastat Plus Cabozantinib Fails to Improve PFS in Advanced or Metastatic RCC

The combination of telaglenastat plus cabozantinib failed to result in a significant improvement in progression-free survival in patients with advanced or metastatic renal cell carcinoma.

The combination of telaglenastat (CB-839) plus cabozantinib (Cabometyx) failed to result in a significant improvement in progression-free survival (PFS) in patients with advanced or metastatic renal cell carcinoma (RCC), missing the primary end point of the phase 2 CANTATA trial (NCT03428217).1

Topline data from the trial showed that the median PFS with the doublet was 9.2 months vs 9.3 months with cabozantinib and placebo (HR, 0.94; P = .065). More than half, or 62%, of patients enrolled to the trial were previously treated with a PD-L1–containing agent, and the treatment arms were well balanced.

Regarding safety, the frequency and severity of the adverse effects experienced by those who received the glutaminase inhibitor were found to be similar to those reported by patients who received cabozantinib/placebo.

The results from the trial will be presented at an upcoming medical conference, according to Calithera Biosciences, Inc, the developer of telaglenastat.

“We are disappointed that the CANTANA did not achieve the 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, 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.”

In the global, randomized, double-blind phase 2 trial, investigators set out to examine the safety and efficacy of telaglenastat plus cabozantinib compared with cabozantinib/placebo in patients with advanced or metastatic RCC who had previously received 1-2 lines of systemic treatment, including at least 1 VEGF-targeted antiangiogenic or nivolumab (Opdivo)/ipilimumab (Yervoy). A total of 444 participants were enrolled to CANTATA at multiple centers on a global scale.

To be eligible for enrollment, patients had to have a Karnofsky performance score of greater than or equal to 70%, measurable disease per RECIST v1.1 criteria, and acceptable hepatic, renal, cardiac, and hematologic function.2

If patients previously received cabozantinib, another MET inhibitor, or telaglenastat, they could not participate. Additionally, if they had received any other anticancer therapy within 2-6 weeks, they were not included. Those with untreated or active brain metastases or central nervous system cancer defined per the trial protocol, were not permitted.

The primary end point of the trial was PFS per blinded independent review. Key secondary end points comprised overall survival and PFS per investigator assessment in accordance with RECIST v1.1 criteria.

Previously, the addition of telaglenastat to everolimus (Afinitor) was found to improve PFS vs single-agent everolimus in heavily pretreated patients with advanced or metastatic RCC. In the phase ENTRATA trial (NCT03163667), the median PFS with the doublet was 3.8 months vs 1.9 months with everolimus monotherapy (HR, 0.64; 95% CI, 0.34-1.20; one-sided, P = .079).3 This trial provided the proof of concept to examine the agent further in RCC.

The clinical-stage biopharmaceutical company announced that it will focus its financial resources on the ongoing phase 2 KEAPSAKE trial (NCT042655534), which is examining telaglenastat in combination with standard of care in the frontline treatment of patients with lung cancer that harbors KEAP1/NRF2 mutations. They will also focus resources on examining the arginase inhibitor CB-280 in patients with cystic fibrosis.


  1. Calithera Biosciences reports CANTATA study of telaglenastat in renal cell carcinoma did not achieve primary endpoint. News release. Calithera Biosciences, Inc. January 4, 2021. Accessed January 4, 2021.
  2. CANTATA: CB-839 with cabozantinib vs. cabozantinib with placebo in patients with metastatic renal cell carcinoma (CANTATA). Updated October 14, 2019. 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). Ann Oncol. 2019;50(suppl 5):889-890. doi:10.1093/annonc/mdz394.048