On November 4, 2020 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage biotechnology company focused on discovering and developing novel small-molecule drugs for the treatment of cancer and other life-threatening diseases, reported the expansion of the company’s ongoing clinical trial evaluating telaglenastat in combination with Pfizer’s CDK 4/6 inhibitor palbociclib (IBRANCE) (Press release, Calithera Biosciences, NOV 4, 2020, View Source [SID1234569849]). This Phase 1/2 study, which is being conducted by Calithera, will be expanded to include an additional cohort of patients with pancreatic ductal adenocarcinoma (PDAC) whose tumors harbor mutations in both KRAS and CDKN2A.

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"There is a strong rationale to target KRAS and CDKN2A mutated tumors with the combination of palbociclib and telaglenastat," said Susan Molineaux, PhD, president and chief executive officer of Calithera. "Mutations in CDKN2A lead to upregulation of both CDK4/6 activity and glutamine utilization in cancer cells. By inhibiting these activities simultaneously with the telaglenastat-palbociclib combination, we hope to have a measurable impact on pancreatic cancer, which still has very few viable treatment options."

Telaglenastat blocks glutamine consumption in tumor cells, which, due to specific genetic alterations such as mutations in KRAS and CDKN2A, often become dependent on increased metabolism of glutamine. Approximately 50 percent of PDAC patients harbor mutations in both KRAS and CDKN2A. In preclinical studies with KRAS-mutated cancer models, telaglenastat showed synergistic anti-tumor effects when used in combination with CDK4/6 inhibitors, such as palbociclib, enhancing cell cycle arrest and blocking cancer cell proliferation. In the ongoing Phase 1/2 clinical trial (NCT03965845), encouraging efficacy and safety of the combination was observed in PDAC patients treated in the dose escalation phase of the trial.

The new cohort of the Phase 1/2 clinical trial will be evaluating the safety and anti-tumor activity of telaglenastat in combination with palbociclib in patients with advanced, metastatic PDAC whose tumors harbor mutations in both KRAS and CDKN2A. The ongoing Phase 1/2 trial is currently enrolling patients with colorectal cancer and non-small cell lung cancer whose tumors harbor mutations in KRAS.