Calithera Biosciences Initiates Phase 1/2 Trial of Telaglenastat in Combination with the PARP Inhibitor Talazoparib
Calithera Biosciences (NASDAQ:CALA) has announced the first patietn has been treated in its Phase 1/2 open-label clinical trial of the glutaminase inhibitor telaglenastat (CB-839) together with Pfizer’s (NYSE:PFE) poly adenosine diphosphate ribose polymerase inhibitor talazoparib, called Talzenna, in patients with advanced or metastatic solid tumors. As quoted in the press release: “The initiation of this … Continued
Calithera Biosciences (NASDAQ:CALA) has announced the first patietn has been treated in its Phase 1/2 open-label clinical trial of the glutaminase inhibitor telaglenastat (CB-839) together with Pfizer’s (NYSE:PFE) poly adenosine diphosphate ribose polymerase inhibitor talazoparib, called Talzenna, in patients with advanced or metastatic solid tumors.
As quoted in the press release:
“The initiation of this clinical trial of telaglenastat in combination with talazoparib marks the first of two clinical trials that will evaluate telaglenastat with approved Pfizer therapeutics as part of this collaboration,” said Susan Molineaux, PhD, president and chief executive officer of Calithera. “We believe these new combination trials have the potential to broaden the opportunities for telaglenastat to improve patient outcomes.”
Preclinical studies have shown that telaglenastat synergizes with PARP inhibitors to impair DNA synthesis, enhance DNA damage and block cancer cell proliferation. The combination of telaglenastat with PARP inhibitors has demonstrated synergistic activity in a number of preclinical cancer models, including renal cell carcinoma (RCC), triple negative breast cancer (TNBC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), ovarian cancer and prostate cancer. In October 2018, Calithera entered into a clinical trial collaboration agreement with Pfizer to evaluate telaglenastat in two clinical trials. The first trial is a combination of telaglenastat with talazoparib and the second trial is a combination of telaglenastat with palbociclib, also known as Ibrance®. As part of this agreement, Pfizer will provide palbociclib and talazoparib, as well as financial support.
The Phase 1/2 trial (NCT03875313) will evaluate the safety and efficacy of the combination of telaglenastat plus talazoparib in patients with locally advanced/metastatic RCC, TNBC and CRC that are refractory or intolerant to standard therapies. The trial will evaluate the potential of telaglenastat to sensitize tumors to talazoparib in patients regardless of mutations in the BRCA gene.
Telaglenastat is an investigational, novel glutaminase inhibitor specifically designed to block glutamine consumption in tumor cells. Tumors commonly exhibit metabolic alterations that increase their dependence on glutamine. In preclinical studies, telaglenastat produced synergistic antitumor effects when used in combination with standard-of-care therapies.
