LAG-3 inhibitor lags on OS outcome in advanced melanoma


By Michael Woodhead

21 Mar 2022

Updated results from the RELATIVITY-047 trial in patients with advanced melanoma show that differences in overall survival and objective response rate seen with a relatlimab/nivolumab combination over nivolumab monotherapy did not reach statistical significance.

New data presented at the ASCO March Plenary Series by Professor Georgina Long of the Melanoma Institute Australia, based on a median follow-up of 19.3 months of 714 patients, showed that the median OS was not yet reached with LAG-3 and PD-1 immune checkpoint inhibitors but was 34.1 months with nivolumab (HR 0.80; 95% CI [0.6, 1.0]; P = .0593).

The OS difference with relatlimab-nivolumab compared to nivolumab was 77% vs. 71.6% at 12 months, 63.7% vs. 58.3% at 24 months and 55.8% vs. 48.8% at 36 months.

The objective response rate at median follow up was 43.1% for patients who received relatlimab and nivolumab, as compared with 32.6% of patients who received nivolumab. Complete response rates with the combination versus monotherapy were 16.3% and 14.2%, respectively.

More grade 3 and 4 treatment-related adverse events were observed in the relatlimab and nivolumab group (21.1%) compared to the nivolumab group (11.1%).

According to the study investigators the adverse events were deemed manageable and those associated with relatlimab and nivolumab were similar to those seen with other immune-oncology agents and no new information on any new or known adverse events were observed.

While it was disappointing that the interim results did not match the statistically significant benefits previously reported in PFS with relatlimab-nivolumab, the study authors said the differences in OS were ‘clinically meaningful’

“These findings provide additional evidence of the benefit of two checkpoint inhibitors over only one and supports the combination of nivolumab and relatlimab, which had a manageable safety profile, as a potential new treatment option for patients with advanced melanoma,” said Professor Georgina Long, who is chair of melanoma medical oncology and translational research at the Melanoma Institute Australia at the University of Sydney.

Her comments were supported by Dr Allison Betof Warner, ASCO Expert in Melanoma, who said the updated data from RELATIVITY-047 further supported the use of nivolumab plus relatlimab over single agent anti-PD-1 therapy for patients who have previously untreated advanced melanoma.

“Combination therapy demonstrated higher overall response rate and continued to show superior progression-free survival compared to nivolumab in exchange for only a modest increase in side effects,” she said.

“If approved, I expect that nivolumab plus relatlimab will become a standard first-line regimen for the treatment of unresectable or metastatic melanoma.”

This research was funded by Bristol Myers Squibb.

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