Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: Results from the open-label, randomised, phase II FRACTION-RCC trial Journal Article
| Authors: | Choueiri, T. K.; Kuzel, T. M.; Tykodi, S. S.; Verzoni, E.; Kluger, H.; Nair, S.; Perets, R.; George, S.; Gurney, H.; Pachynski, R. K.; Folefac, E.; Castonguay, V.; Lee, C. H.; Vaishampayan, U.; Miller, W. H. Jr; Bhagavatheeswaran, P.; Wang, Y.; Gupta, S.; DeSilva, H.; Lee, C. W.; Escudier, B.; Motzer, R. J. |
| Article Title: | Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: Results from the open-label, randomised, phase II FRACTION-RCC trial |
| Abstract: | Background: 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. Methods: 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. Results: 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. Conclusions: 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. © 2024 The Authors |
| Keywords: | adult; controlled study; treatment response; aged; major clinical study; clinical feature; fatigue; advanced cancer; diarrhea; drug safety; side effect; follow up; ipilimumab; progression free survival; phase 2 clinical trial; nausea; randomized controlled trial; vomiting; renal cell carcinoma; pruritus; rash; cancer center; immunotherapy; multicenter study; kaplan meier method; triacylglycerol lipase blood level; programmed death 1 ligand 1; lymphocyte activation gene 3 protein; demographics; immune checkpoint inhibitor; nivolumab; human; male; female; article; advanced renal cell carcinoma; relatlimab |
| Journal Title: | ESMO Open |
| Volume: | 9 |
| Issue: | 12 |
| ISSN: | 2059-7029 |
| Publisher: | European Society for Medical Oncology |
| Date Published: | 2024-12-01 |
| Start Page: | 104073 |
| Language: | English |
| DOI: | 10.1016/j.esmoop.2024.104073 |
| PROVIDER: | scopus |
| PMCID: | PMC11667034 |
| PUBMED: | 39642635 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus |
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