Therapeutic Areas

Calithera’s drug discovery platform targets key metabolic enzymes that are critical to pathways that provide tumor and other diseased cells with the nutrients they need for survival and growth, or that are important in activating the body’s own immune system to target and kill disease-causing cells.

When these metabolic pathways are blocked, cancer cells are deprived of critical nutrients and stop growing or die, whereas normal cells are largely unaffected. Many types of tumors show altered metabolic pathways that are fundamentally different from normal cells. These changes provide the potential to develop agents that target these altered pathways, but have less toxicity than standard cytotoxic agents.

Our initial focus is in renal cell carcinoma(RCC), where telaglenastat (CB-839) has demonstrated activity in its first randomized Phase 2 trial (ENTRATA) and is currently being evaluated in a pivotal Phase 2 trial (CANTATA). ENTRATA is a randomized, double-blind, Phase 2 study that compared telaglenastat in combination with everolimus vs. placebo with everolimus in patients with advanced renal cell carcinoma. The ENTRATA trial met its primary endpoint of improved progression-free survival. CANTATA (NCT03428217) is a global, randomized, double-blind Phase 2 study designed with registrational intent comparing telaglenastat in combination with cabozantinib vs. placebo with cabozantinib in patients with advanced or metastatic renal cell carcinoma.

Another area of focus is non-small cell lung cancer (NSCLC) with mutations that activate the NRF2/KEAP1 pathway. A key subset of these activated genes regulate the uptake and metabolism of glutamine and the synthesis of glutathione, making tumors that harbor these mutations dependent on the activity of glutaminase. The clear mechanistic rationale and high unmet medical need in the NSCLC population have motivated a randomized clinical study (NCT04265534) that will evaluate telaglenastat, in combination with standard of care chemo-immunotherapy in front line NSCLC patients with tumors that harbor mutations in either KEAP1 or NRF2 that activate this pathway. The randomized, double-blind trial will enroll approximately 120 patients with stage IV non-squamous NSCLC with NRF2 or KEAP1 mutation. Patients will be randomized to receive telaglenastat or placebo, in combination with pembrolizumab, carboplatin and pemetrexed. Co-primary endpoints are safety and investigator assessed progression-free survival, and an interim analysis is planned. This trial is expected to begin in the third quarter of 2020.

Telaglenastat is also being evaluated in multiple combination trials. In addition to these company sponsored clinical trials, telaglenastat is also being studied in investigator-sponsored trials.

Renal Cell Carcinoma (RCC)

According to the National Cancer Institute, renal cell carcinoma is diagnosed in approximately 65,000 people each year in the United States. Renal cell carcinoma is the most common type of kidney cancer. Approximately 50% of renal cell carcinoma patients will require chemotherapy at some point to treat their disease. Clear cell type is the most common form of kidney cancer, comprising 75%-85% of cases.