Agent That Starves Tumor Cells May Improve Survival in Metastatic RCC

OncLive reports that a trial in the USA of novel glutaminase inhibitor CB-839, may provide a survival benefit in combination with cabozantinib (Cabometyx) by cutting off the energy supply to tumor cells in patients with metastatic renal cell carcinoma (RCC). Although there are several treatment options available for patients with metastatic RCC, some patients still have progressive disease after prior lines of therapy.
The combination with CB-839 is being investigated in the randomized, phase II CANTATA study (NCT03428217). The study is enrolling participants with measurable clear cell RCC who have received 1 or 2 prior lines of therapies, including at least 1 antiangiogenic therapy or nivolumab (Opdivo) combined with ipilimumab (Yervoy).
“[The trial] will bring a first-in-its-class glutaminase-targeted drug as an addition to our armamentarium to treat this disease,” said Nizar M. Tannir, MD, professor and deputy chairman in the department of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center in Houston. Investigators hope to improve on the outcomes from cabozantinib alone for patients who have received a tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor. Cabozantinib is FDA approved as a second-line treatment following prior TKI therapy.
The trial’s primary endpoint is progression-free survival (PFS), which will be assessed by an independent radiology committee. Secondary endpoints include overall survival (OS) and PFS as assessed by investigators.
CB-839 is an oral inhibitor of glutaminase, which is essential to the conversion of glutamine, an amino acid, into glutamate, which aids cell signaling. By inhibiting this process, CB-839 deprives tumor cells of energy, the availability of glutamate to the cells is decreased, and cell proliferation is blocked.¹
Inhibition of glutaminase is preferentially inhibitory to tumor cells over normal cells due to abnormal tumor metabolism, according to Tannir, the lead principal investigator and chair of the steering committee for the CANTATA trial. In addition, the glutamine that builds up in tumor cells as a result of the inhibition of glutaminase helps to fuel T-cell growth, which may increase the tumor-fighting potential of CB-839.
 
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