Calithera Biosciences Initiates Phase 1/2 Trial


Calithera Biosciences, Inc. recently announced treatment of the first patient in a Phase 1/2 open-label clinical trial of the glutaminase inhibitor telaglenastat (CB-839) in combination with Pfizer’s CDK 4/6 inhibitor palbociclib, also known as Ibrance. The study will evaluate the safety and anti-tumor activity of telaglenastat plus palbociclib in patients with KRAS-mutated colorectal cancer (CRC) and KRAS-mutated non-small cell lung cancer (NSCLC). 

“Preclinical data suggest that telaglenastat and palbociclib have synergistic activity in KRAS-mutated tumors, and may offer a new approach to the challenges associated with treating KRAS-mutated cancers,” said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. “We are excited to launch this second clinical trial with Pfizer and are hopeful that the telaglenastat-palbociclib combination could fill a significant treatment gap for patients and medical professionals.”

Telaglenastat is designed to block glutamine consumption in tumor cells. Genetic alterations, such as mutations in KRAS, can cause cancer cells to increase metabolism of glutamine. In preclinical studies with KRAS-mutated cancer models, telaglenastat showed synergistic antitumor effects when used in combination with CDK4/6 inhibitors, such as palbociclib, enhancing cell cycle arrest and blocking cancer cell proliferation.  The Phase 1/2 clinical trial (NCT03965845) will evaluate the safety and anti-tumor activity of the telaglenastat plus palbociclib combination in patients with locally advanced/metastatic KRAS-mutated CRC and KRAS-mutated NSCLC that are refractory or intolerant to standard therapies.

This is the second trial initiated by Calithera as part of an ongoing clinical trial agreement with Pfizer. The first trial, which is investigating the combination of telaglenastat with the PARP inhibitor talazaporib in patients with renal cell carcinoma (RCC), triple negative breast cancer (TNBC) and CRC began enrolling patients in March 2019. As part of the agreement, Pfizer is providing palbociclib and talazoparib, as well as financial support.

Telaglenastat is an investigational selective oral inhibitor against human glutaminase, a critical enzyme that enables cancer cells to utilize glutamine for metabolism and survival.Tumors commonly exhibit metabolic alterations that increase their dependence on glutamine. In pre-clinical studies, telaglenastat has demonstrated synergistic antitumor activity when used in combination with standard-of-care therapies. Telaglenastat in combination with everolimus met the primary endpoint of improving PFS compared to everolimus with placebo in ENTRATA, a randomized  Phase 2 clinical study. The compound is currently being evaluated in multiple ongoing combination trials, including with cabozantinib in the global, pivotal Phase 2 CANTATA study.

Calithera Biosciences is a clinical-stage biopharmaceutical company pioneering the discovery and development of targeted therapies that disrupt cellular metabolic pathways to preferentially block tumor cell growth and enhance immune-cell activity. Driven by a commitment to rigorous science and a passion for improving the lives of people impacted by cancer and other life-threatening diseases, Calithera is advancing a pipeline of first-in-clinic, oral therapeutics to meaningfully expand treatment options available to patients. Calithera is headquartered in South San Francisco, California. For more information about Calithera, please visit www.calithera.com.

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