Treatment with telaglenastat in combination with cabozantinib did not improve progression-free survival in patients with advanced or metastatic renal cell carcinoma when compared with cabozantinib alone, missing the primary end point of the phase 2 CANTANA clinical trial.
Treatment with telaglenastat in combination with cabozantinib (Cabometyx) did not improve progression-free survival (PFS) in patients with advanced or metastatic renal cell carcinoma (RCC) when compared with cabozantinib alone, missing the primary end point of the phase 2 CANTANA clinical trial (NCT03428217), announced Calithera Biosciences, Inc, in a press release.
Topline results showed that the median PFS among patients treated with telaglenastat plus cabozantinib was 9.23 months compared with 9.3 months in patients who received cabozantinib with placebo, according to blinded independent review. The hazard ratio for the difference between the 2 treatment arms was 0.94with a P value of 0.65. The 2 treatment arms had a comparable frequency and severity of adverse events.
Full results from CANTANA will be presented during an upcoming medical meeting.
“We are disappointed that the CANTATA trial did not achieve its primary endpoint, 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,” said Susan Molineaux, PhD, president, and chief executive officer of Calithera, in a statement.
The goal of the global, randomized, double-blind trial is to determine the efficacy and safety of telaglenastat in combination with cabozantinib compared with cabozantinib alone in patients with advanced or metastatic RCC who have been treated with 1 or 2 prior lines of systemic therapy, which included patients who received at least 1 vascular endothelial growth factor (VEGF) pathway targeted anti-angiogenic therapy or nivolumab (Opdivo) in combination with ipilimumab (Yervoy). The study also assessed overall survival (OS) and PFS per RECIST v1.1 criteria as secondary end points.
To be included in the study, patients were required to have documented histological or cytological diagnosis that has a clear-cell component, a Karnofsky Performance Score of at least 70%, measurable disease per RECIST 1.1, and adequate hepatic, renal, cardiac, and hematologic function. All patients enrolled were adults who received 1 or 2 lines of prior therapy for advanced or metastatic RCC.
Individuals were excluded from the CANTANA trial if they received prior cabozantinib or another MET inhibitor, anticancer therapy within 2 to 6 weeks of randomization, and prior gastric surgery or small bowel resection. Patients with untreated brain metastases, central nervous system cancer, active infection with human immunodeficiency virus, Hepatitis B or C virus, and other conditions that may interfere with study treatment were also excluded. Patients were also ineligible if they could not to discontinue proton-pump-inhibitor use before randomization.
With the CANTANA study coming to a close, Calithera Biosciences, Inc, highlights the promise of telaglenastat even though the addition of the drug to cabozantinib did not reach the threshold for significance.
Molineaux stated, “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 phase 2 randomized, multicenter, double-blind KEAPSAKE trial (NCT04265534), patients with first-Line, metastatic KEAP1/NRF2-mutated, nonsquamous, non–small cell lung cancer are treated with telaglenastat in combination with pembrolizumab (Keytruda) and chemotherapy. The co-primary end points in the study include investigator-assessed PFS, safety/tolerability, and the recommended phase 2 dose. The secondary end points include the objective response rate, duration of response, and OS.
Calithera Biosciences reports CANTATA study of telaglenastat in renal cell carcinoma did not achieve primary endpoint. News release. Calithera Biosciences, Inc. January 4, 2020. Accessed January 4, 2020. https://yhoo.it/3rTmXas