Andrea B. Apolo, MD
As reported in the Journal of Clinical Oncology by Andrea B. Apolo, MD, and colleagues, findings in expansion cohorts of a phase I study showed the activity of cabozantinib/nivolumab alone or with the addition of ipilimumab in patients with advanced/metastatic genitourinary (GU) tumors.
Study Details
In the U.S. multicenter study, 120 patients enrolled between July 2025 and July 2020 received either:
- Cabozantinib plus nivolumab (n = 64; consisting of cabozantinib at 40 mg plus nivolumab at 1 or 3 mg/kg every 2 weeks
- Cabozantinib, nivolumab, and ipilimumab (n = 56; consisting of cabozantinib and nivolumab plus ipilimumab at 1 or 3 mg/kg every 3 weeks for four doses).
Cabozantinib plus nivolumab expansion cohorts consisted of patients with metastatic urothelial carcinoma, metastatic renal cell carcinoma, and rare GU tumors; cabozantinib, nivolumab, and ipilimumab expansion cohorts consisted of patients with metastatic urothelial carcinoma, metastatic renal cell carcinoma, penile cancer, and squamous cell carcinoma of the bladder and other rare GU tumors. A total of 108 patients, including 59 in the cabozantinib plus nivolumab group and 49 in the cabozantinib, nivolumab, and ipilimumab group, were evaluable for response. The primary outcome measure of the study was objective response.
Key Findings
The median follow-up was 49.2 months. Among all 108 evaluable patients, the objective response rate was 38%, with complete response in seen in 11% and median duration of response lasting 20.2 months. Objective response rates included: 42.4% among 33 patients with metastatic urothelial carcinoma (complete response in 21.2%; median response duration = 28.0 months); 62.5% among 16 patients with metastatic renal cell carcinoma (complete response in 12.5%; median response duration = 16.7 months); 85.7% among 7 patients with squamous cell carcinoma of the bladder (complete response in 28.6%; median response duration = 25.8 months); 44.4% among 9 patients with penile cancer; and 50.0% among 2 patients with renal medullary carcinoma.
Among all evaluable patients in the cabozantinib plus nivolumab group, the objective response rate was 44.1%, with complete response in 15.3% and a median response duration of 25.8 months. Among all evaluable patients in the cabozantinib, nivolumab, and ipilimumab group, the objective response rate was 30.6%, with complete response in 6.1% and a median response duration of 14.5 months.
Median overall survival was 15.5 months among all patients and 51.8 months among 41 patients with objective response.
Among the total of 120 patients in the safety population, grade ≥ 3 adverse events occurred in 84% of the cabozantinib plus nivolumab group and 80% of the cabozantinib, nivolumab, and ipilimumab group. The most common adverse events were elevated lipase (14%), fatigue (13%), and hypertension (13%) in the cabozantinib plus nivolumab group and lipase elevation (20%), fatigue (16%), and hypophosphatemia (14%) in the cabozantinib, nivolumab, and ipilimumab group. No treatment-related deaths were observed.
The investigators concluded, “[Cabozantinib plus nivolumab] and [cabozantinib, nivolumab, and ipilimumab] demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell renal cell carcinoma; urothelial carcinoma; and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.”
Dr. Apolo, of the Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute Intramural Program and the Cancer Therapy Evaluation Program. For full disclosures of the study authors, visit ascopubs.org.
