Dr. Meric-Bernstam on CB-839 Plus Cabozantinib in RCC

Funda Meric-Bernstam, MD, chair, Department of Investigational Cancer Therapeutics, medical director, Institute for Personalized Cancer Therapy, professor of medicine, The University of Texas MD Anderson Cancer Center, discusses the combination of CB-839 plus cabozantinib (Cabometyx) in patients with renal cell carcinoma (RCC).

Cancer cell metabolism is increasingly becoming acknowledged as an important therapeutic target. Glutamine and glucose are key nutrients, while glutaminase converts glutamine into glutamate, enhancing its utilization. The fact that glutaminase is expressed at high levels in RCC supports the rationale for combining the glutaminase inhibitor CB-839 with a VEGF TKI. In vivo, anti-tumor activity is increased with this combination, Meric-Bernstam says.

A phase I study looking at this combination was presented at the 2019 Genitourinary Cancers Symposium. Cabozantinib was given at 60 mg per day, while CB-839 was administered twice daily at 600 mg or 800 mg. In the study of 13 patients with RCC, 11 had clear cell disease and 2 had papillary disease. Overall, the combination appeared to be well tolerated, with the recommended dose of CB-839 being 800 mg twice daily—the same as the monotherapy’s recommended dose.