Calithera Biosciences (CALA) announced two new clinical trial collaborations to evaluate Pfizer’s (PFE) palbociclib, also known as Ibrance, and the investigational dual-mechanism poly, or ADP-ribose, polymerase, or PARP, inhibitor talazoparib, each in combination with Calithera’s glutaminase inhibitor CB-839. As part of the collaboration, Pfizer will provide palbociclib and talazoparib, as well as financial support. Preclinical data suggest that CB-839, which is designed to starve tumor cells of the key nutrient glutamine, synergizes with CDK4/6 inhibitors by enhancing cell cycle arrest and blocking cancer cell proliferation. The combination of CB-839 with CDK4/6 inhibitors has demonstrated synergistic activity in a number of preclinical cancer models, including colorectal cancer, or CRC, non-small cell lung carcinoma, or NSCLC, triple negative breast cancer, or TNBC and ER+ breast cancer. Based on these data, Calithera will initiate a Phase 1/2 clinical trial of the combination of CB-839 plus palbociclib in patients with KRAS mutated CRC and patients with KRAS mutated NSCLC in Q1 of 2019. CB-839 also synergizes with PARP inhibitors to impair DNA synthesis, enhance DNA damage, and block cancer cell proliferation. The combination of CB-839 with PARP inhibitors has demonstrated synergistic activity in a number of preclinical cancer models, including renal cell carcinoma, TNBC, CRC, NSCLC, ovarian cancer and prostate cancer. Based on these data, Calithera will initiate a Phase 1/2 clinical trial of the combination of CB-839 plus talazoparib in patients with RCC, and TNBC in Q1 of 2019.
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