The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology study in patients with aRCC (FRACTION-RCC) was designed to assess new immuno-oncology (IO) combinations in patients with advanced renal cell carcinoma (aRCC). We present results in IO-naive patients treated with nivolumab (NIVO) + relatlimab (RELA) or NIVO + ipilimumab (IPI) in track 1.
The open-label, randomised, phase II FRACTION-RCC trial enrolled patients with aRCC from 32 hospitals and cancer centres across six countries. Patients were enrolled in track 1 (IO-naive) or track 2 (IO-experienced). IO-naive patients were stratified by previous tyrosine kinase inhibitor therapy and randomised to NIVO (240 mg) + RELA (80 mg) intravenously once every 2 weeks or NIVO (3 mg/kg) + IPI (1 mg/kg) intravenously once every 3 weeks for four doses, followed by NIVO (480 mg) once every 4 weeks, each up to ∼2 years. The primary endpoints were objective response by investigator (RECIST version 1.1), duration of response (DOR), and progression-free survival (PFS) rate at 24 weeks. Safety was a secondary endpoint; biomarker analyses were exploratory.
FRACTION-RCC enrolled patients between 2 February 2017 and 23 January 2020. In track 1, 30 patients each were treated with NIVO + RELA or NIVO + IPI (clinical database lock, 1 November 2021). With NIVO + RELA [median follow-up, 48.6 months; interquartile range (IQR) 46.9-51.7 months], objective response was 30% [95% confidence interval (CI) 15% to 49%], with 33 weeks (95% CI 16-53 weeks) median DOR. The PFS rate at 24 weeks was 43% (95% CI 25% to 60%). With NIVO + IPI (median follow-up, 48.7 months; IQR 47.1-52.0 months), the objective response was 20% (95% CI 8% to 39%), with the median DOR not reached (95% CI 33 weeks-not estimable). The PFS rate at 24 weeks was 49% (95% CI 29% to 66%). Higher baseline lymphocyte activation gene 3 (LAG-3) and programmed death-ligand 1 (PD-L1) expression levels were detected among track 1 NIVO + RELA responders. Grade 3-4 treatment-related adverse events were reported in 4/30 (13%) patients treated with NIVO + RELA and 10/30 (33%) patients treated with NIVO + IPI. No deaths were attributed to study treatments.
Results showed antitumour activity and manageable safety with NIVO + RELA. Findings also support NIVO + IPI as an effective combination regimen in IO-naive patients with aRCC.
ESMO open. 2024 Dec 05 [Epub ahead of print]
T K Choueiri, T M Kuzel, S S Tykodi, E Verzoni, H Kluger, S Nair, R Perets, S George, H Gurney, R K Pachynski, E Folefac, V Castonguay, C-H Lee, U Vaishampayan, W H Miller, P Bhagavatheeswaran, Y Wang, S Gupta, H DeSilva, C-W Lee, B Escudier, R J Motzer
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: ., Division of Hematology/Oncology/Cell Therapy, Rush University Medical Center, Chicago, IL, USA., Department of Medicine, Division of Hematology and Oncology, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Section of Medical Oncology, Yale Cancer Center, New Haven, CT, USA., Department of Hematology/Oncology, Lehigh Valley Topper Cancer Institute, Allentown, PA, USA., Division of Oncology, Clinical Research Institute at Rambam, Rambam Health Care Campus, Technion - Israel Institute of Technology, Haifa, Israel., Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia., Siteman Cancer Center, Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA., Department of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA., Department of Medicine, CHU de Quebec -Université Laval, Quebec City, Quebec, Canada., Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA; Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, USA., Segal Cancer Centre and Lady Davis Institute, Jewish General Hospital, Montréal, Quebec, Canada; Department of Oncology, McGill University, Montréal, Quebec, Canada., Department of Biometrics and Data Sciences, Bristol Myers Squibb, Princeton, NJ, USA., Department of Translational Medicine Oncology, Bristol Myers Squibb, Princeton, NJ, USA., Department of Global Drug Development, Bristol Myers Squibb, Princeton, NJ, USA., Department of Clinical Trials, Bristol Myers Squibb, Princeton, NJ, USA., Department of Medical Oncology, Gustave Roussy, Villejuif, France., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.