ASCO GU 2019: CANTATA: Randomized, International, Double-Blind Study of CB-839 Plus Cabozantinib versus Cabozantinib Plus Placebo in Patients with Metastatic Renal Cell Carcinoma

San Francisco, CA ( Glutamine metabolism is upregulated in renal cell carcinoma (RCC) and is involved with tumor cell proliferation and survival. CB-839 is an inhibitor of the enzyme glutaminase (GLS), which is found in mitochondria and is involved with glutamine metabolism. Notably, it is administered orally. Cabozantinib is an anti-angiogenic, anti-tumor growth VEGFR2/MET/AXL inhibitor. In preclinical RCC models, CB-839 and cabozantinib were found to have synergistic anti-tumor activity. A phase 1 study showed that the combination of the two drugs had favorable safety and efficacy, with 50% overall response rate (ORR) by RECIST 1.1 and 100% disease control rate in 10 patients with clear cell advanced or metastatic RCC (mRCC).

CANTATA is an international, multi-center, randomized, double-blind, phase 2 study evaluating CB-839 + cabozantinib versus placebo + cabozantinib in patients with mRCC. Key eligibility criteria include 1-2 prior lines of systemic therapy including >= 1 anti-angiogenic therapy or the combination of nivolumab + ipilimumab, KPS ≥70%, measurable disease by RECIST 1.1, and adequate hepatic, renal, cardiac and hematologic function. Key exclusion criteria include no prior treatment with MET inhibitors, including cabozantinib, receipt of recent anticancer therapy, prior gastrointestinal surgery that may impede drug absorption, HIV, and hepatitis B/C. The study start date is 2018 and it is projected to come to completion in 2022 after enrollment of 300 patients.

The patients are randomized 1:1 and treatment is continued in 28-day cycles until disease progression or unacceptable toxicity. Patients are stratified by prior PD-1/PD-L-1 immunotherapy and by their prognostic risk group. The primary outcome measure is progression-free survival (PFS) by independent radiology review using RECIST 1.1 criteria, and secondary outcome measures are PFS by the investigator and overall survival (OS). Safety and quality of life measures are also assessed.

This trial will provide information about the safety and efficacy of CB-839, a first in-clinic (oral) metabolic inhibitor in combination with cabozantinib, an anti-angiogenic agent in patients with mRCC and progression after 1-2 prior systemic treatments.

Presented by: Nizar Tannir, MD, FACP, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Texas

Written by: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, @selmasic at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA