A prospective, single-arm, phase 2 study shows activity after treatment intensification with a triplet combination regimen in patients with metastatic renal cell carcinoma with variant histologies (RCCvh), especially those without chromophobe histology.
Results of the study will be presented at the American Society of Clinical Oncology 2023 Annual Meeting.
Bradley Alexander McGregor, MD, and colleagues designed NCT04413123 to assess a cabozantinib, nivolumab, and ipilimumab combination in patients with metastatic RCCvh. Eligible patients had to have an Eastern Cooperative Oncology Group performance status of 0-1 and may have received a previous line of therapy, excluding immunotherapy or cabozantinib.
A total of 40 patients underwent a baseline biopsy and received intravenous nivolumab (3 mg/kg) and ipilimumab (1 mg/kg) Q3 weeks for 4 cycles, followed by intravenous nivolumab (480 mg) Q4 weeks. Cabozantinib was administered continuously at a dose of 40 mg daily, though reductions to 20 mg daily and 20 mg every other day were allowed.
The primary end point was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors, version 1.1. The secondary end point was safety.
At data cutoff, 38 patients had received at least 1 study drug; 45% (n=17) had received all 4 doses of nivolumab, 18% (n=7) had received 3 doses of nivolumab, and 37% (n=14) had received ≤2 doses.
Twenty-three patients, 15 of whom received 4 cycles of nivolumab plus ipilimumab, received a median of 5 cycles of nivolumab maintenance. Seventy-one percent (n=27) and 13% (n=5) had cabozantinib dose reduction to 20 mg and 20 mg every other day, respectively.
After a median follow-up of 8.4 months, objective response was achieved in 8 patients (ORR, 21%; 2-sided 80% CI, 13%-32%) and 19 patients had stable disease. Researchers noted that median duration of response was not reached, with 5 patients maintaining response after 6 months. Additionally, median progression-free survival was 8.9 months (95% CI, 4.2-12.7).
A total of 28 patients developed treatment-related grade 3 or higher toxicities. Eleven patients required high-dose steroids, and 5 patients discontinued all study drugs due to toxicity. No grade 5 toxicity has been reported to date.
In their concluding remarks, Dr. McGregor and colleagues noted that the cabozantinib, nivolumab, and ipilimumab combination showed promise in patients with RCCvh, especially in those with papillary histology and not in those with chromophobe histology; 5 of the 11 patients with chromophobe histology experienced progressive disease while on treatment.
They noted that an additional cohort of 20 patients is enrolling with a cabozantinib starting dose of 20 mg daily.
