FRACTION-RCC: a randomized, open-label, adaptive, phase 2 study of nivolumab in combination with other immuno-oncology agents in patients with advanced Renal Cell Carcinoma (RCC) CC Taitt,1 RJ Motzer,2 TK Choueiri,3 BJ Escudier,4 T Kuzel,5 MA Carducci,6 S Nair,7 SS Tykodi,8 S Tannenbaum-Dvir,1 M Wind-Rotolo,1 KL Simonsen,1 PM Fracasso1, M Maira-Arce1 1BMS, NJ; 2Memorial Sloan Kettering Cancer Center, NY; 3Dana-Farber Cancer Institute, MA; 4Gustave Roussy Cancer Centre, France; 5Rush University Medical Center, IL; 6Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, MD; 7Lehigh Valley Health Network, PA; 8University of Washington and Fred Hutchinson Cancer Research Center, WA
Background:Nivolumab is approved for patients with advanced RCC after prior antiangiogenic therapy based on superior overall survival vs everolimus (CM025; Motzer RJ, et al. N Engl J Med. 2015).Nivolumab has also shown promising antitumor activity in combination with ipilimumab in patients with metastatic RCC, supporting the rationale that nivolumab in combination with other IO agents or targeted therapies may improve outcomes in patients with advanced RCC. Given the rapid development of novel IO agents, traditional study designs may not efficiently evaluate all possible combinations.Fast Real-time Assessment of Combination Therapies in Immuno-Oncology (FRACTION) is an innovative clinical trial program with a rolling, adaptive platform design that allows for the addition of new regimens as well as the withdrawal of ineffective regimens. Here we describe the study concept, key design components, and first IO treatment combinations of FRACTION-RCC. Methods: FRACTION-RCC is envisioned to accelerate the development of the next generation of IO combinations for patients with metastatic RCC. Patients with advanced RCC with a clear-cell component will be enrolled based on prior IO treatment and randomized to receive nivolumab plus BMS-986016 or nivolumab plus ipilimumab. Enrollment is continuous and may offer patients consecutive treatment options based on treatment exposure and response. Primary endpoints include objective response rate, duration of response, and progression-free survival rate at 24W. The secondary endpoint is safety. Biomarker analyses will also be performed.New treatment combinations will be added over time to explore their potential benefits and provide a continuous flow of treatment options for patients whose cancer progresses on existing treatments.