On December 5, 2017 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported that updated clinical data from its lead product candidate CB-839, a first-in-class glutaminase inhibitor, will be presented at the 2017 San Antonio Breast Cancer Symposium, December 5-9, 2017 in San Antonio, Texas (Press release, Calithera Biosciences, DEC 5, 2017, View Source [SID1234535249]). The data demonstrate the clinical activity and tolerability of CB-839 in combination with paclitaxel, and highlight the unique mechanism of action of CB-839 in patients with advanced/metastatic triple negative breast cancer (TNBC). Based on these data, Calithera has opened a Phase 2 trial exploring the treatment combination in both first line and late line metastatic TNBC patients.

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"Effective treatment for triple negative breast cancer in the advanced and metastatic population remains a significant unmet need. In our Phase 1 study, we were pleased to have observed responses in patients who were heavily pretreated and the Phase 2 study will help us further understand the role of CB-839 in inhibiting glutaminase to help control the progression of cancer in advanced metastatic TNBC patients," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.

In a poster presentation representing an update from data presented at SABCS 2016, Dr. Kevin Kalinsky from Columbia University Medical Center will present, "Phase I study of CB-839, a first-in-class inhibitor of glutaminase, in combination with paclitaxel in patients with advanced triple negative breast cancer," (Abstract PD3-13). Eligible patients must have locally advanced/metastatic TNBC, with no restrictions on prior exposure to taxanes, or the number of prior therapies. As of October 23, 2017, 49 triple negative breast cancer patients had been treated with doses of CB-839 of 400, 600 or 800 mg bid in combination with 80 mg/m2 IV paclitaxel, weekly, three weeks out of four; 44 were evaluable for response. Patients were heavily pretreated, having received a median of 3 prior therapies for advanced metastatic disease. A majority of patients had received prior taxane therapy in either the neo-adjuvant (37%) or metastatic setting (51%). Among all evaluable patients treated with CB-839 doses of at least 600 mg bid (n=37), there were 8 partial responses (22%) and disease control (response or stable disease) in 22 patients (59%). Among African Americans, there was a 36% response rate in patients who had received previous taxanes in the metastatic setting; all responders were refractory to prior taxanes. Exploratory biomarker analysis shows a trend for the strongest clinical benefit occurring in patients with LAR and/or desmoplastic stromal gene expression signatures1.

The combination of CB-839 and paclitaxel has been well tolerated to date, with adverse events that have been primarily low grade and reversible. Consistent with the previous report, there was one case of dose-limiting, recurrent grade 3 neutropenia at the 400 mg dose level, which led to a reduction in the dose of paclitaxel for that patient. The most frequent adverse event ≥ Grade 3 was neutropenia (27%). A low rate of ≥ Grade 3 peripheral neuropathy (4.2%) was observed despite 88% of the patients having prior taxane exposure. 1Lehmann et al., J Clin Invest 2011; Chen et al, Cancer Inform 2012; Jovanovic et al BMC Cancer 2017; Saleh et al, Cancer Research 2017

About CB-839 Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types, in combination with standard of care agents