Phase 2 Study Tests Cabo/Nivo/Ipi in RCCvh

Bradley McGregor, MD, senior physician at Dana-Farber Cancer Institute, and director of Clinical Research at the Lank Center for Genitourinary Oncology, discusses the rationale behind the multi-institutional, prospective, single-arm phase 2 trial (NCT04413123) of cabozantinib (Cabometyx), nivolumab (Opdivo), and ipilimumab (Yervoy) for the treatment of patients with renal cell carcinoma with variant histologies (RCCvh).

Patients with metastatic RCCvh were eligible for enrollment in the study if they had an ECOG performance status of 0-1. Patients also were eligible if they had received 1 prior line of therapy, excluding immunotherapy or cabozantinib.

Once enrolled, patients underwent a baseline biopsy and were treated with nivolumab 3 mg/kg and ipilimumab 1 mg/kg via intravenous (IV) infusion every 3 weeks for 4 cycles. This was then followed by IV nivolumab 480 mg every 4 weeks. Further, patients received cabozantinib continuously at a dose of 40 mg daily, and investigators assessed the primary end point of objective response rate by RECIST 1.1, and safety as a secondary end point.

Transcription:

0:10 | When we think about renal cell carcinoma, there's been a ton of advances in the treatment of renal cell carcinoma. However, a lot of those have been related to clear cell renal cell carcinoma, which is the most common type of kidney cancer accounting for 80% of renal cell carcinomas. But we know there's 20% of patients who present with RCC with variant histologies, what we call, non-clear cell, and we have been looking to make advances in that field.

0:36 | For a long time, there have been incremental advances, but there have been some exciting advances recently. We were building upon what we saw with COSMIC-313 [NCT03937219] with [nivolumab, ipilimumab, and cabozantinib], vs nivolumab and ipilimumab, and tried to bring that triplet into RCC with variant histology.

0:49 | This was a single arm, phase 2 trial which took 40 patients with renal cell carcinoma with variant histology who have received up to 1 prior to therapy, excluding immunotherapy or cabozantinib. They went on to receive induction with nivolumab and ipilimumab, and cabozantinib 40 mg daily, followed by nivolumab with cabozantinib until unacceptable toxicity or progression.