1. Phase 1 study of CB-839, a small molecule inhibitor of glutaminase (GLS) in combination with paclitaxel (Pac) in patients (pts) with triple negative breast cancer (TNBC)
- Author
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Taofeek K. Owonikoko, James J. Harding, Angela DeMichele, James W. Mier, Melinda L. Telli, Richard D. Carvajal, Manish R. Patel, Jeffrey R. Infante, Othon Iliopoulos, Pamela N. Munster, Mark K. Bennett, Keith W. Orford, Funda Meric-Bernstam, and Rana R. McKay
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Glutaminase ,Pharmacology ,Glutamine ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Paclitaxel ,chemistry ,Tolerability ,In vivo ,030220 oncology & carcinogenesis ,Internal medicine ,Cancer cell ,Toxicity ,medicine ,business ,Triple-negative breast cancer - Abstract
1011Background: CB-839 is a first-in-class highly selective inhibitor of GLS, a key enzyme in the utilization of glutamine by many cancer cells. TNBC is very glutaminolytic, with high GLS expression and a high glutamate:glutamine ratio, and highly dependent on glutamine for growth. CB-839 has selective activity in most in vitro and in vivo TNBC preclinical models tested. CX-839-001 is an ongoing Phase 1 basket trial of CB-839 as monotherapy and in combination with approved agents. BID dosing of CB-839 with meals provided optimal PK and tolerability and achieved robust inhibition of GLS in blood and tumors. After achieving strong GLS inhibition with acceptable toxicity and observing a TNBC patient (pt) with a 23% reduction in tumor burden on study for >18 months, a combination arm testing CB-839 with Pac (Pac-CB) for TNBC was opened. Methods: Patients with metastatic TNBC received escalating doses of CB-839 (400-800 BID) in combination with a fixed weekly Pac dose (80 mg/kg on Days 1, 8, 15 of 28 day cycle...
- Published
- 2016
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