Nivolumab plus relatlimab superior to nivolumab alone in previously untreated metastatic or unresectable melanoma

The RELATIVITY-047 study investigates the potential benefits of combined inhibition of LAG-3 and PD-1 inhibitors by means of administration of nivolumab plus relatlimab (NIVO + RELA) versus nivolumab alone in the treatment of metastatic or unresectable melanoma. After two-years of follow-up, a consistent benefit was observed with NIVO + RELA vs. NIVO for progression-free survival, overall survival and objective response rate.

In the global, randomised, double-blind phase II/III RELATIVITY-047 study, treatment with nivolumab plus relatlimab (NIVO + RELA) significantly improved progression-free survival (PFS) versus NIVO alone. Along with this improvement in PFS, a higher objective response rate (ORR) and a non-statistically significant improvement in overall survival (OS) were also noted with the combination NIVO + RELA versus NIVO alone. At ASCO 2023, the 2-year follow-up results of the RELATIVITY-047 study were presented.

Study design

Patients, randomised 1:1, received either NIVO + RELA (480 mg + 160 mg respectively, N= 355) or NIVO (480 mg, N= 359) alone. Patients were stratified by LAG-3, PD-L1, BRAF, and AJCC v8 M stage. Primary endpoint measures included PFS as per RECIST V1.1 assessed by BICR, while secondary endpoints encompassed OS and ORR per BICR.

Results

The median follow-up time was 25.3 months. At this timepoint, the combination of NIVO + RELA still displayed a benefit over NIVO alone in terms of PFS (median PFS 10.2 vs. 4.6 months; HR[95%CI]: 0.81[0.67-0.97]), OS (median OS not reached vs. 33.2 months; HR[95% CI]: 0.82[0.67-1.02]), and ORR (44% vs. 34%). The median duration of response was not reached in either the NIVO + RELA arm [95%CI: 39.4-not yet reached] or in the NIVO arm [95%CI: 39.8-not yet reached]), and the combination was reportedly preferred over NIVO alone across key subgroups. NIVO + RELA also had a reported benefit on melanoma-specific survival (MSS). Patients receiving NIVO + RELA also had a sustained benefit vs. NIVO beyond initial treatment and first progression. The median melanoma-specific survival for the combination treatment was not reached, and was 46.7 months for the NIVO alone arm, with an HR[95% CI] of 0.77[0.61-0.97]. In the combination arm, 36.9% of patients received subsequent systemic therapy compared to 37.9% who received NIVO alone. Adverse events related to the treatment were observed in 17.2% of patients on NIVO + RELA, whereas 8.6% of patients reportedly had treatment-related adverse events on NIVO alone. Furthermore, 22% of patients receiving the combination treatment displayed a grade 3-4 adverse event versus 12% on NIVO alone. In total, 6 treatment-related deaths were reported, 4 of which were related to the combination treatment, and 2 to NIVO alone. Importantly, no new treatment-related deaths have been reported since the previous analysis.

Conclusion

NIVO + RELA displays a benefit effect on PFS, OS, and ORR over NIVO alone, and MSS was longer when treated with the combination versus NIVO alone. Safety of the NIVO + RELA regimen was consistent with previous reports, with no new or unexpected safety signals, and remained manageable with a favourable risk/benefit profile.

Reference

Tawbi H.A, et al. Nivolumab (NIVO) plus relatlimab (RELA) vs NIVO in previously untreated metastatic or unresectable melanoma: 2-year results from RELATIVITY-047. Presented at ASCO 2023; Abstract 9502.