Combo Immunotherapy Regimen Significantly Improves Progression-Free Survival in Advanced Melanoma


Findings from the phase 3 RELATIVITY-047 trial were presented at the 2021 ASCO Annual Meeting.


Treatment with a dual immunotherapy regimen targeting different checkpoints can delay disease progression in patients with advanced melanoma, according to study results presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

During a virtual presscast, Evan J Lipson, MD, from Bloomberg-Kimmel Institute for Cancer Immunotherapy and the Sidney Kimmel Cancer Comprehensive Cancer Center, Johns Hopkins University, presented the initial phase 3 results from RELATIVITY-047, highlighting the treatment combination of relatlimab (RELA) plus nivolumab (NVO) in this patient population.

RELATIVITY-047 is a phase 3 global trial that compares RELA plus NIVO with NIVO alone in patients with previously untreated unresectable or metastatic melanoma.

NIVO works by blocking programmed cell death 1 (PD-1), whereas RELA blocks another immune checkpoint called lymphocyte-activation gene 3 (LAG-3).

“Although these drugs work through distinct pathways, they have a common goal which is to unleash and attack by immune T cells against cancer,” said Lipson, who is the lead author of the study. Lipson noted that previous trials leading up to the current study showed that administration with RELA plus NIVO caused tumors to shrink in some patients with advanced melanoma that was relapsed/refractory to PD-1 alone.

A total of 714 patients in the study received either a fixed-dose combination of RELA 160 mg plus NIVO 480 mg administered as a single intravenous infusion or nivolumab 480 mg alone.

The results showed that median progression-free survival (PFS) was significantly longer with NIVO and RELA compared with NIVO alone (10.1 versus 4.6 months, respectively).

“The PFS benefit appeared relatively early in the course of therapy,” Lipson said, noting that the difference could be seen at 12 weeks, which was when the first on-treatment imaging was performed. At 1 year, PFS rates were 47.7% for patients receiving the immunotherapy combination and 36.0% for those receiving nivolumab.

RELA plus NIVO was associated with a manageable safety profile and reflected the typical safety profile seen with immune checkpoint inhibitors, according to Lipson. Grade 3/4 treatment-related adverse effects (TRAEs) were more common among patients receiving the combination regimen (18.9%) versus nivolumab alone (9.7%). There were 3 treatment-related deaths among patients receiving the dual therapy and 2 in the nivolumab monotherapy group. TRAEs resulted in therapy discontinuation in 14.6% and 6.7% of patients, respectively.

Overall, administration of RELA plus NIVO in patients with previously untreated unresectable or metastatic melanoma led to a significant improvement in PFS compared with NIVO alone.

“Our findings demonstrate that RELA plus NIVO is a potential novel treatment option for this patient population,” Lipson said. “Additionally, and importantly, this is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CTLA-4 and PD-1, for which blockade appears to have clinical benefits.”


  1. Lipson EJ, Abdul-Hassan Tawbi H, Schadendorf D, et al. Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in first-line advanced melanoma: Primary phase III results from RELATIVITY-047 (CA224-047). 2021 American Society of Clinical Oncology Annual Meeting; June 4-8, 2021; virtual. Doi: 10.1200/JCO.2021.39.15_suppl.9503
  2. Lipson EJ. Relatlimab (RELA) + nivolumab (NIVO) versus NIVO in first-line advanced melanoma: Primary phase 3 results from RELATIVITY-047 (CA224-047). Presscast. 2021 American Society of Clinical Oncology Annual Meeting; May 14, 2021; virtual.

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