FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy.

The role and sequencing of combination immuno-oncology (IO) therapy following progression on or after first-line IO therapy has not been well-established. The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) program is an open-label, phase 2 platform trial designed to evaluate multiple IO combinations in patients with advanced renal cell carcinoma (aRCC) who progressed during or after prior IO therapy. Here, we describe the results for patients treated with nivolumab plus ipilimumab. For enrollment in track 2 (reported here), patients with histologically confirmed clear cell aRCC, Karnofsky performance status ≥70%, and life expectancy ≥3 months who had previously progressed after IO (anti-programmed death 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)) therapy were eligible. Previous treatment with anti-CTLA-4 therapy plus anti-PD-1/PD-L1 therapy precluded eligibility for enrollment in the nivolumab plus ipilimumab arm. Patients were treated with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks for up to 2 years or until progression, toxicity, or protocol-specified discontinuation. The primary outcome measures were objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) rate at 24 weeks. Secondary outcomes were safety and tolerability up to 2 years. Overall survival (OS) was a tertiary/exploratory endpoint. Overall, 46 patients were included with a median follow-up of 33.8 months. The ORR was 17.4% (95% CI, 7.8 to 31.4) with eight (17.4%) patients achieving partial response. Stable disease was achieved in 19 (41.3%) patients, while 14 (30.4%) had progressive disease. Median DOR (range) was 16.4 (2.1+ to 27.0+) months. The PFS rate at 24 weeks was 43.2%, and median OS was 23.8 (95% CI, 13.2 to not reached) months. Grade 3-4 immune-mediated adverse events were reported in seven (15.2%) patients. No treatment-related deaths were reported. Patients with aRCC treated with nivolumab plus ipilimumab may derive durable clinical benefit after progression on previous IO therapies, including heavily pretreated patients, with a manageable safety profile that was consistent with previously published safety outcomes. These outcomes contribute to the knowledge of optimal sequencing of IO therapies for patients with aRCC with high unmet needs.

NCT02996110.

Journal for immunotherapy of cancer. 2022 Nov [Epub]

Toni K Choueiri, Harriet Kluger, Saby George, Scott S Tykodi, Timothy M Kuzel, Ruth Perets, Suresh Nair, Giuseppe Procopio, Michael A Carducci, Vincent Castonguay, Edmund Folefac, Chung-Han Lee, Sebastien J Hotte, Wilson H Miller, Shruti Shally Saggi, Chung-Wei Lee, Heshani Desilva, Prabhu Bhagavatheeswaran, Robert J Motzer, Bernard Escudier

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA ., Department of Medical Oncology, Yale University Yale Cancer Center, New Haven, Connecticut, USA., Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA., Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Division of Hematology/Oncology/Cell Therapy, Rush University Medical Center, Chicago, Illinois, USA., Division of Oncology, Rambam Health Care Campus, Haifa, Israel., Department of Hematology/Oncology, Lehigh Valley Health Network, Allentown, Pennsylvania, USA., Division of Medical Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy., Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA., Department of Medicine, CHU de Quebec-Universite Laval, Montreal, Quebec, Canada., Department of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Department of Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada., Division of Oncology, Department of Medicine, McGill University, Montreal, Québec, Canada., Department of Global Regulatory Science, Bristol Myers Squibb, Princeton, New Jersey, USA., Department of Clinical Trials, Bristol Myers Squibb, Princeton, New Jersey, USA., Department of Global Drug Development, Bristol Myers Squibb, Princeton, New Jersey, USA., Department of Biometrics and Data Sciences, Bristol Myers Squibb, Princeton, New Jersey, USA., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Gustave Roussy, Villejuif, Île-de-France, France.

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