RELATIVITY-104 study

Prof Nicolas Girard, thoracic oncologist at Institut Curie, Paris, presented data from the Relativity 104 trial, which evaluated nivolumab plus relatlimab and chemotherapy versus nivolumab plus chemotherapy as a first-line treatment for metastatic NSCLC. Relatlimab is a LAG-3 blocking antibody that enhances anti-tumour immune responses, already approved in combination with nivolumab for advanced melanoma.

This randomised trial aimed to determine whether adding relatlimab would enhance the efficacy of chemo-immunotherapy. A total of 309 patients were stratified by histology, PD-L1 expression, and performance status. The primary endpoint was response rate. However, the study did not show a significant difference between the two arms in the intent-to-treat population.

A pre-specified analysis of subgroups revealed a benefit in patients with PD-L1 expression ≥1% and non-squamous histology. In this group, the addition of relatlimab increased the response rate from 40% to 58%, with a PFS HR of 0.55, and a median PFS of nearly 12 months.

Regarding safety, adding relatlimab did not alter the safety profile, with comparable adverse events in both arms.

Moving forward, a phase 3 study will compare pembrolizumab plus chemotherapy versus the combination of relatlimab, nivolumab and chemotherapy in non-squamous NSCLC patients with PD-L1 expression between 1% and 49%.

This trial suggests that combining multiple checkpoint inhibitors could improve first-line treatment of metastatic non-squamous NSCLC. However, biomarkers are needed to personalise strategies and enhance long-term OS. Escalating treatment intensity may be necessary to achieve this goal.