Relatlimab plus nivolumab shows ‘consistent PFS benefit’ in advanced melanoma
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Relatlimab plus nivolumab continued to demonstrate a PFS benefit compared with nivolumab alone for patients with previously untreated metastatic or unresectable melanoma, according to a study presented during an ASCO Plenary Series session.
The latest results of RELATIVITY-047, a global, randomized, double-blind phase 2/phase 3 study, appeared consistent with the primary analysis, with no new safety signals, researchers reported.
“Double checkpoint inhibitor therapy works — it is not a redundant strategy,” Georgina V. Long, AO, BSc, PhD, MBBS, FRACP, FAHMS, co-medical director of Melanoma Institute Australia and chair of melanoma medical oncology and translational research at Melanoma Institute Australia and Royal North Shore Hospital at University of Sydney, told Healio.
“These data further validate the nivolumab (Opdivo, Bristol Myers Squibb) combination with relatlimab (BMS-986016, Bristol Myers Squibb) as a potential new treatment option in patients with advanced melanoma,” Long said during the presentation. “The nivolumab-relatlimab combination continued to demonstrate a consistent PFS benefit with this longer follow-up: a 22% reduction in risk [for] progression or death.”
Background and methodology
Previously, researchers reported the addition of relatlimab to nivolumab resulted in significantly longer PFS among treatment-naive patients with advanced melanoma, with data showing the combination of the human IgG4 lymphocyte-activation gene 3 (LAG-3)-blocking antibody (relatlimab) and the anti-PD-1 agent (nivolumab) had a manageable safety profile.
“Immune checkpoint inhibitors have absolutely revolutionized treatment options for patients with cancer around the globe, but particularly for patients with advanced melanoma,” Long said. “New treatment combinations are needed to improve the benefit, the efficacy vs. the risk, and toxicity profile.”
The latest analysis of RELATIVITY-047 included updated PFS data and results of OS and overall response rate.
The trial included 714 patients with previously untreated, unresectable or metastatic melanoma and an ECOG performance status of 0 to 1. Long and colleagues randomly assigned them 1:1 to 480 mg nivolumab plus 160 mg relatlimab given via IV every 4 weeks (n = 355; median age, 63 years; 40.8% women), or nivolumab alone (n = 359; median age, 62 years; 42.6% women).
PFS per RECIST version 1.1 as assessed by blinded independent central review served as the primary endpoint, with OS and ORR by blinded independent central review as secondary endpoints.
Key findings
At median follow-up of 19.3 months, researchers reported updated median PFS of 10.2 months (95% CI, 6.5-14.8) with the relatlimab-nivolumab combination compared with 4.6 months (95% CI, 3.5-6.4) with nivolumab alone (HR = 0.78; 95% CI, 0.6=0.9). Median OS had not been reached (95% CI, 34.2 to not reached) with relatlimab-nivolumab vs. 34.1 months (95% CI, 25.2 to not reached) with nivolumab alone (HR = 0.8; 95% CI, 0.6-1).
“The nivolumab-relatlimab combination demonstrated a clinically meaningful improvement in OS, a secondary endpoint, but this was not statistically significant, with a 20% reduction in the risk [for] death,” Long reported. “Overall survival rates were numerically improved at 12, 24 and 36 months vs. nivolumab alone, and OS favored the combination across all stratification factors, including LAG-3 and PD-L1 expression.”
Additional analysis showed a confirmed ORR of 43.1% (95% CI, 37.9-48.4) with relatlimab-nivolumab vs. 32.6% (95% CI, 27.8–37.7) with nivolumab, and researchers observed complete responses in 16.3% of patients on the combination vs. 14.2% on nivolumab alone. Long called the relatlimab-nivolumab combination’s safety profile manageable and reported no new or unexpected safety signals.
“(I was surprised) how well-tolerated the doublet was, and how a randomized controlled trial conducted in a different era (eg, compared with -067 in 2013) may have different outcomes for the same drug (ie, the control arm nivolumab),” Long told Healio. “This demonstrates the importance of the randomization.”
Implications
Long said next steps in the research would include how to sequence the therapy with other checkpoint inhibitor combinations, such as ipililumab (Yervoy, Bristol Myers Squibb) and nivolumab.
Allison Betof Warner, MD, PhD, medical oncologist specializing in melanoma and clinical trials of new immunotherapeutic and targeted therapeutic agents at Memorial Sloan Kettering Cancer Center, said the updated results of RELATIVITY-047 further support the use of the combination therapy vs. single-agent anti-PD-1 therapy among patients with previously untreated advanced melanoma.
“Combination therapy demonstrated higher overall response rate and continued to show superior progression-free survival compared [with] nivolumab in exchange for only a modest increase in side effects,” Warner said in a press release. “If approved, I expect that nivolumab plus relatlimab will become a standard first-line regimen for the treatment of unresectable or metastatic melanoma.”
References:
Long GV, et al. Abstract 360385. Presented at: ASCO Plenary Series (virtual); March 15, 2022.
Nivolumab with relatlimab continues to show benefit in patients with advanced melanoma. https://www.asco.org/about-asco/press-center/news-releases/nivolumab-relatlimab-continues-show-benefit-patients-advanced. Published March 14, 2022. Accessed March 16, 2022.
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Long GV, et al. Abstract 360385. Presented at: ASCO Plenary Series (virtual); March 15, 2022.
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