Biomarker analyses from patients enrolled in the RELATIVITY-047 trial revealed that relatlimab added to nivolumab has robust anti-tumor activity among patients with advanced melanoma with lower CD8+ T cell infiltration.

These results were presented at the European Society for Medical Oncology Congress in Madrid, Spain, by lead author Evan J. Lipson, MD, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland. 

According to study results, “[nivolumab plus relatlimab] demonstrated significant progression-free survival (PFS) benefit vs [nivolumab],” stated Dr Lipson and coauthors. Here, “exploratory biomarker analyses were conducted to elucidate mechanisms underlying [nivolumab plus relatlimab] activity and identify patients more likely to derive benefit from the combination.” 

Blood samples from patients treated in both treatment arms were collected at baseline and 4 weeks after completion of treatment. To assess the relationship between biomarkers and treatment response, flow cytometry was used to identify pharmacodynamic changes in immune cell populations (lymphocyte activation gene-3 [LAG-3]- or programmed death-1 [PD-1]-expressing CD4+ and CD8+ T cells, and natural killer [NK] cells). Immunohistochemistry (IHC) was used to analyze baseline tissue samples for major histocompatibility complex class 1 or 2 expression, and CD8 infiltration and multiplex IHC was used to analyze HALO images of LAF3+ and LAG3− CD8+ T cells. 

In this analysis, nivolumab plus relatlimab was found to significantly increase multiple peripheral immune cell types. Response to nivolumab plus relatlimab was associated with increased LAG-3+ CD4+ T cells at week 4. However, on-treatment modulation of peripheral CD8+ T cells was not associated with nivolumab plus relatlimab efficacy. Patients who responded to nivolumab plus relatlimab had higher baseline PD-1+ CD8+ and ICOS+ CD8+ T cell numbers.  

In the tumor microenvironment (TME), higher baseline MHC-1 and MHC-2 was associated with improved efficacy in both treatment arms. Patients treated with nivolumab plus relatlimab who had low/medium TME CD8 infiltration experienced a PFS benefit, and benefit was also experienced among patients with high TME CD8 infiltration, only when LAG-3 was also expressed. 

According to Dr Lipson and coauthors, “TME analysis suggests [relatlimab] activity is particularly robust in tumors with lower CD8+ T-cell infiltration; peripheral data suggest CD4+ T-cell modulation may be key to its distinct mechanism of action, [however] further exploratory biomarker analyses are warranted to identify [patients] who may derive maximal benefit from [nivolumab plus relatlimab].”

Source: 

Lipson EJ, Dolfi S, Tang H, et al. Unraveling relatlimab (RELA)-specific biology using biomarker analyses in patients with advanced melanoma treated with nivolumab (NIVO)+RELA or NIVO alone in RELATIVITY-047. Presented at the 2023 ESMO Congress; October 20- 24, 2023; Madrid, Spain. Abstract LBA51