ASCO 2020: FRACTION-RCC: Innovative, High-Throughput Assessment of Nivolumab + Ipilimumab for Treatment-Refractory Advanced Renal Cell Carcinoma

( The treatment landscape for patients with metastatic renal cell carcinoma has evolved rapidly over the past few years, marked by the introduction of immunotherapeutic approaches utilizing checkpoint inhibitors. While a variety of monotherapy and combination therapies have now been approved and widely adopted in this setting, nivolumab and ipilimumab combination therapy in the first line setting and nivolumab in the second line setting following tyrosine kinase inhibitor were among the first utilized for patients with advanced renal cell carcinoma.

The Fast Real-Time Assessment of Combination Therapies in Immuno-Oncology (FRACTION-RCC) study (NCT02996110) is an open-label, randomized phase II trial utilizing an adaptive design to test a variety of immune-oncology combination therapies rapidly. In this adaptive design, there are currently a number of treatment arms: nivolumab and ipilimumab; nivolumab and relatlimab; nivolumab and BMS-986205; and, nivolumab and BMS-813160.


The study aims to accrue 200 patients with advanced renal cell carcinoma who have at least one lesion with measurable disease, a life expectancy of at least 3 months, and a Karnofsky performance status exceeding 70%. Patients with inadequately treated central nervous system metastases, those with autoimmune disease, and those needing daily oxygen were excluded. The study is currently ongoing with a planned primary completion date of January 2022. The primary outcomes are objective response rate, duration of response, and progression-free survival. Secondary outcomes include adverse events and serious adverse events.

In an oral abstract session at the 2020 American Society of Clinical Oncology Virtual Annual Meeting, Dr. Choueiri and colleagues presented the preliminary results of patients receiving nivolumab and ipilimumab in patients with advanced renal cell carcinoma who had progressed on checkpoint inhibitor therapy.

In this analysis, the authors report of 46 patients (of whom 45 had progressed on previous checkpoint inhibitor therapy) who were randomized to receive nivolumab (3mg/kg) and ipilimumab (1mg/kg) every three weeks for 4 cycles followed by nivolumab 480mg every 4 weeks, beginning 6 weeks after the completion of the nivolumab and ipilimumab induction, and continued for up to two years or until progression, toxicity, or protocol-specified discontinuation. In the report, the authors assessed the primary endpoints of confirmed objective response rate (ORR; per investigator using RECIST v1.1), duration of response (DOR), and progression-free survival probability at week 24 as well as the safety secondary outcomes.

Among the 46 included patients, there was a wide range of pre-treatment including 0 (n = 1), 1 (n = 10), 2 (n = 12), 3 (n = 10), or ≥4 (n = 13) prior lines of therapy. All pretreated pts had prior anti-PD-(L)1-, none had prior anti-CTLA-4- therapy and 37 had prior TKI-based therapy. Each of the patients who had at least one line of therapy (n=45) had progressed on anti-PD-(L)1 as the most recent therapy. The vast majority of patients had clear cell renal cell carcinoma (n=44 of 46).

The Median follow-up of this cohort was 8.9 months. The objective response rate was 15.2% (7 of 46 patients): 7 patients achieved a partial response and none achieved complete response. Among the 7 patients with partial response, the duration of response ranged from 2 to more than 19 months with 5 of 7 patients having an ongoing response at the time of data cut off. Six of these 7 patients with partial responses had received at least two prior lines of therapy.


Treatment related adverse events were reported in 36 patients (78.3%). Fatigue (19.6%), rash (19.6%), and diarrhea (17.4%) were the most commonly reported events. Severe adverse events (grade 3-4) were less common, occurring in 13 patients (28.3%). Serious adverse events included diarrhea (8.7%), elevated lipase (6.5%), and elevated amylase (6.5%) were the most common. Treatment-related immune-mediated adverse events occurred in 22 patients (47.8%) of which rash (19.6%), diarrhea (17.4%), and elevated AAT (8.7%) were the most common. There were no treatment-related deaths.

These data suggest that the combination of nivolumab and ipilimumab may offer durable partial responses in patients with pre-treated advanced renal cell carcinoma, including those who had progression on prior checkpoint inhibitor therapy. Ongoing accrual and analysis of the FRACTION-RCC trial will assess novel immune-oncologic approaches in patients with advanced renal cell carcinoma.

Presented by: Toni K. Choueiri, MD, Jerome and Nancy Kohlberg Professor of Medicine, Harvard Medical School, Attending Physician, Solid Tumor Oncology, Director, Genitourinary (GU) Oncology Disease, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute

Co-Authors: Harriet M. Kluger, Saby George, Scott S. Tykodi, Timothy M. Kuzel, Ruth Perets, Suresh Nair, Giuseppe Procopio, Michael Anthony Carducci, Vincent Castonguay, Edmund Folefac, Chung-Han Lee, Sebastien J. Hotte, Wilson H. Miller, Shruti S. Saggi, David Gold, Robert J. Motzer, Bernard Escudier

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Contact: @WallisCJD on Twitter at the 2020 ASCO Annual Meeting, Virtual Scientific Program #ASCO20, May 29-31, 2020.
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