SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Exelixis, Inc. (NASDAQ:EXEL) today announced updated data from expansion cohorts in a phase 1 trial of cabozantinib in combination with either nivolumab or nivolumab plus ipilimumab in patients with refractory genitourinary tumors. The primary endpoint of the trial is to determine the dose-limiting toxicity and recommended phase 2 doses of the doublet and triplet combinations. The findings will be presented during a poster session (Abstract #515) on February 9 at the 2018 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU), which is being held in San Francisco, California, February 8-10, 2018.

The updated data reported results from 78 patients treated with cabozantinib and nivolumab with or without ipilimumab. The initial part of the study determined the recommended dose for each treatment at four dose levels. In all, 49 patients were treated with the doublet combination of cabozantinib and nivolumab and 29 patients were treated with the triplet combination of cabozantinib, nivolumab and ipilimumab. Nineteen patients with mUC were evaluable for response with a median follow up of 15.7 months. Thirteen patients with previously treated mRCC were evaluable for response.

For the mUC cohort, the ORR across all treatment groups was 42 percent (2 CRs and 6 PRs of 19 patients) and the DCR (DCR = CR, PR and SD) was 84 percent. Seven of eight (88 percent) mUC patients with an objective response had not progressed at the time of the data cut-off. Median PFS in this patient population was 12.8 months and the overall survival rate at 12 months was 77 percent. Among the 13 patients with mRCC who were evaluable for response, ORR was 54 percent (7 PRs of 13 patients) and the DCR was 100 percent.

In the overall study, the ORR in 64 evaluable patients was 36 percent (3 CRs and 20 PRs) with a median duration of response (DOR) of 24 months. 78 patients were included in the safety analysis. Expected immune-related events including colitis, meningitis, hepatitis, pneumonitis and endocrine disorders occurred at a low frequency.

“The updated analysis of this trial shows that cabozantinib, in combination with nivolumab or in combination with nivolumab plus ipilimumab, demonstrates an acceptable tolerability profile and encouraging rates of durable responses in the previously treated metastatic urothelial carcinoma and metastatic renal cell carcinoma cohorts,” said Andrea Apolo, M.D., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, and principal investigator of the trial. “Evidence of clinical activity, including encouraging progression free survival in a patient population that has a significant unmet need, gives us motivation to further evaluate these combination therapies.”

No dose-limiting toxicity was observed in the study. Based on general tolerability, the recommended cabozantinib dose for the expanded dose cohorts and for future late stage evaluation has been determined as cabozantinib at 40 mg daily oral dose combined with nivolumab at 3 mg/kg every 2 weeks and ipilimumab at 1 mg/kg every 3 weeks for 4 doses.

Treatment-related grade 3 or 4 adverse events (>5 percent of patients) observed in the doublet combination included lipase increased (16 percent), hypophosphatemia (14 percent), neutrophil count decreased (12 percent), hypertension (8 percent), fatigue (6 percent) and infection (6 percent). Grade 3 or 4 adverse events (>5 percent of patients) observed in the triplet combination included hypophosphatemia (21 percent), lymphocyte count decreased (14 percent), lipase increased (14 percent), ALT increased (10 percent), AST increased (10 percent), hypertension (10 percent), diarrhea (10 percent), hypokalemia (10 percent), fatigue (7 percent), hyponatremia (7 percent) and amylase increased (7 percent). Grade 3 or 4 immune-related adverse events for the doublet combination included colitis, aseptic meningitis and hepatitis (one patient each) and for the triplet combination were colitis (one patient) and hepatitis (two patients). There were no treatment-related deaths.

“We greatly value our collaboration with NCI-CTEP on this study, which suggests that the combination of cabozantinib with immune checkpoint inhibitors may have the potential to improve outcomes for patients with genitourinary malignancies, including urothelial and renal cell carcinoma,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “These phase 1 results have informed the current phase 3 trial of such combination therapy in previously untreated advanced or metastatic renal cell carcinoma, as well as future studies exploring these combinations across a range of advanced genitourinary cancers including urothelial cancer.”