Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE).

In this phase II response-adaptive trial, we investigated the rational application of immune checkpoint blockade in renal cell carcinoma (RCC; ClinicalTrials.gov identifier: NCT03203473).

We enrolled patients with metastatic RCC with no prior checkpoint inhibitor exposure.

All patients received nivolumab alone with subsequent arm allocation based on response. Patients with a confirmed partial response (PR) or complete response (CR) within 6 months discontinued nivolumab and were observed (arm A). Patients with stable disease or progressive disease (PD) after no more than 6 months of nivolumab received two doses of ipilimumab (arm B). The primary endpoints were the proportion of patients with PR/CR at 1 year after nivolumab discontinuation (arm A) and proportion of nivolumab nonresponders who converted to PR/CR after ipilimumab (arm B).

Overall, 83 patients initiated treatment, of whom 96% had clear-cell histology, 51% were treatment naïve, and 67% had intermediate/poor-risk disease. Median follow-up was 19.5 months. Within 6 months, induction nivolumab resulted in a confirmed PR in 12% of patients (n = 10). Fourteen patients were not allocated to a study arm (seven because of toxicity, seven because of PD). Twelve patients (14%) were allocated to arm A and discontinued nivolumab, of whom five (42%; 90% CI, 18% to 68%) remained off nivolumab at ≥ 1 year. Of 57 patients (69%) allocated to arm B, two patients converted to a confirmed PR (4%; 90% CI, 1% to 11%), and no CRs were observed.

In this study, nivolumab followed by two doses of ipilimumab resulted in no CRs and a low PR/CR conversion. The number of patients evaluated for nivolumab discontinuation was too small to assess the value of this approach. Currently, our data do not support a response-adaptive strategy for checkpoint blockade in advanced RCC.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020 Oct 27 [Epub ahead of print]

Rana R McKay, Bradley A McGregor, Wanling Xie, David A Braun, Xiao Wei, Christos E Kyriakopoulos, Yousef Zakharia, Benjamin L Maughan, Tracy L Rose, Walter M Stadler, David F McDermott, Lauren C Harshman, Toni K Choueiri

University of California San Diego, La Jolla, CA., Dana-Farber Cancer Institute, Boston, MA., University of Wisconsin, Carbone Cancer Center, Madison, WI., University of Iowa Health Care, Holden Comprehensive Cancer Center, Iowa City, IA., University of Utah, Salt Lake City, UT., Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC., University of Chicago, Chicago, IL., Beth Israel Deaconess Medical Center, Boston, MA.