Relatlimab/Nivolumab Achieves Clinically Meaningful Improvement in OS for Advanced Melanoma

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Relatlimab plus nivolumab demonstrated reduction in risk of progression or death and numerically improved overall survival compared to nivolumab alone.

Relatlimab plus nivolumab (Opdivo) demonstrated a 22% reduction in risk of progression or death and numerically improved overall survival (OS) rates compared to nivolumab alone. However, statistical significance was not reached for this secondary end point according to results presented during the ASCO Plenary Series: March 2022 Session.

The results are consistent with those of the primary analysis as the study previously met its primary end point of progression-free survival. The combination of relatlimab and nivolumab continues to demonstrate benefit compared to nivolumab alone in patients with previously untreated metastatic or unresectable melanoma, according to findings from the RELATIVITY-047 study (NCT03470922).1

Within the global, randomized, double-blind, phase 2/3 study, RELATIVITY-047, 714 patients were randomized 1:1 and received relatlimab at 160 mg plus nivolumab at 480 mg fixed dose combination or nivolumab at 480 mg alone, given intravenously every 4 weeks.2

Eligibility was open to patients with previously untreated, unrespectable or metastatic melanoma and an ECOG status of either 1 or 0. Some stratification factors included LAG-3, PD-L1, and BRAF.

According to Long, the primary end point of the study was PFS according to RECIST v1.1 which was assessed by blinded independent central review (BICR). Secondary end points included OS and overall response rate (ORR) by BICR, tested hierarchically.

At a median follow-up was 19.3 months, median PFS was 10.2 months (95% CI, 6.4-15.7) with the combination compared to 4.6 months (95% CI, 3.38-5.62) with nivolumab (HR 0.78; 95% CI, 0.644-0.94).3

Median OS was not reached (NR; 95% CI, 34.2NR) with the relatlimab and nivolumab combination while it was 34.1 months (95% CI. 25.2-NR) with nivolumab (HR 0.80; 95% CI, 0.6-1.0; p = .0593). ORR was higher with relatlimab plus nivolumab and the safety profile of the combination remained manageable with no new or unexpected safety signals.

Additionally, OS rates at 12 months were 77.0% (95% CI, 72.2-81.1) for the combination compared to 71.6% (95% CI, 66.6-76.0) for nivolumab alone, and 24 months, OS rates were 63.7% (95% CI, 58.1-68.7) versus 58.3% (95% CI, 52.7-63.4) respectively.

Subsequent systemic therapy rates and types were shown to be similar between treatment groups. Confirmed ORR per BICR was 43.1% (95% CI, 37.9-48.4) with relatlimab and nivolumab versus 32.6% (95% CI, 27.8-37.7) with nivolumab. Complete responses were observed in 16.3% of patients on relatlimab and nivolumab and 14.2% on just nivolumab.

At the secondary analysis looking at OS, relatlimab plus nivolumab demonstrated a clinically meaningful improvement in OS but was not statistically significant. Additionally, there was a 20% reduction in risk of death (HR, 0.80; 95% Cl, 0.64-0.94) and OS rates numerically improved during months 12, 24, and 36, according to Long. Additionally, OS favored this combination versus nivolumab alone across stratification factors which include LAG-3 (1%), and PD-L1 (1%) expression.

The combination of or relatlimab and nivolumab had a manageable safety profile with no new or unexpected safety signals. In 52 (21.1%) patients on relatlimab and nivolumab versus 40 (11.1%) patients on nivolumab, grade 3/4 treatment-related adverse events (TRAEs) were observed.

There were 4 treatment-related deaths in the relatlimab and nivolumab group, which included 1 more than observed in previous analysis, and 2 total in the nivolumab group. Any-grade TRAEs leading to treatment discontinuation were observed in 14.6% patients on relatlimab and nivolumab versus 6.7% nivolumab alone.

“These data further validate [nivolumab plus relatlimab] as a potential new treatment option in patients with advanced melanoma and support the benefit of dual checkpoint inhibition,” said Georgina Long, AO, BSc, PhD, MBBS, FRACP, FAHMS, co-medical director of Melanoma Institute Australia, chair of Melanoma Medical Oncology and Translational Research at MIA and Royal North Shore Hospital, University of Sydney.

References:
1. Long GV, Hodi FS, Lipson EJ, et al. Relatlimab and nivolumab versus nivolumab in previously untreated metastatic or unresectable melanoma: Overall survival and response rates from RELATIVITY-047 (CA224-047). Presented at: ASCO Plenary Series: March 2022 Session; March 15, 2022; virtual. Abstract 360385. Accessed March 15, 2022. https://bit.ly/3KNB9KM
2. Study of relatlimab plus nivolumab versus nivolumab alone in participants with advanced melanoma (RELATIVITY-047). Clinicaltrials.gov. Accessed March 15, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03470922
3.Lipson EJ. Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in first-line advanced melanoma: primary phase III results from RELATIVITY-047 (CA224-047). Presented at: 2021 ASCO Annual Meeting; June 4-8, 2021; Virtual. Abstract 9503.
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