US-based biopharmaceutical firm Exelixis has started a Phase I trial of cabozantinib in combination with nivolumab alone or in combination with nivolumab plus ipilimumab to treat patients with advanced/metastatic urothelial (bladder) and other genitourinary tumors.

Around 66 patients will be enrolled in this open label, non-randomized Phase I trial, which is divided into a dose-escalation phase and an expansion cohort phase.

The trial is sponsored by the US National Cancer Institute (NCI) through cooperative research and development agreements between the NCI's Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis, and both Bristol-Myers Squibb (BMS) and Exelixis.

NCI Genitourinary Malignancies Branch Dr Andrea Apolo is the principal investigator of the trial, which will be conducted by the NCI and includes centers from its Experimental Therapeutics Clinical Trials Network.

Dr Apolo said: "In a previous study, single-agent cabozantinib demonstrated intriguing clinical activity in bladder cancer.

"Now, with this trial, we'll explore the safety and tolerability, and the antitumor activity of the combination of cabozantinib with the immune checkpoint inhibitor nivolumab, alone or together with ipilimumab, in this and other important genitourinary cancer settings."

The trial's primary endpoint is the determination of dose-limiting toxicities (DLT) and a recommended phase II dose (RP2D) for the combination of cabozantinib and nivolumab, and separately, for the combination of cabozantinib, nivolumab and ipilimumab, in patients with genitourinary solid tumors.

Secondary endpoints of the trial include evaluating the activity of the two combinations by objective response rate, as well as progression-free survival (PFS) and overall survival (OS), in a group of patients with urothelial carcinoma of the bladder, urethra, ureter or renal pelvis.

The trial's dose-escalation phase will enroll patients with metastatic genitourinary solid tumors including renal cell carcinoma, urothelial cancer and castration-resistant prostate cancer who have progressed following treatment with at least one standard therapy.

In the trial, around 24 patients will be treated with the combination of cabozantinib plus nivolumab (CaboNivo), and about 18 patients will receive the combination of cabozantinib, nivolumab, and ipilimumab (CaboNivoIpi).

The company said that the starting dose of cabozantinib will be 40mg daily for each combination and can increase up to 60mg daily.

Once the RP2Ds are determined for the combinations of CaboNivo and CaboNivoIpi, the trial will enroll expansion groups of about 12 eligible patients for each combination, for up to 24 patients total in the expansion cohort.

According to the company, patients must have histologically confirmed metastatic, progressive urothelial cancer of the bladder, urethra, ureter, or renal pelvis to be eligible for the expansion cohort.