Addition of Relatlimab to Nivolumab and Chemotherapy Did Not Improve Response Among Patients With Unresectable, Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Cancer

Results from the phase 2 RELATIVITY-060 study demonstrated that the addition of relatlimab, a lymphocyte-activation gene 3 (LAG-3)-blocking antibody, to nivolumab and chemotherapy in the first-line setting did not improve response among patients with unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer with LAG-3 expression ≥1%. 

According to Susanna Hegewisch-Becker, MD, PhD, Hematology-Oncology Practice Eppendorf, Hamburg, Germany, and coauthors, “dual immunotherapies…have resulted in clinical benefit versus chemotherapy for the treatment of multiple tumor types, suggesting that combining nivolumab with other checkpoint inhibitors, such as relatlimab…has the potential for a synergistic effect.” 

In this open-label, multicenter study, 274 patients with unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer were randomized on a 1-to-1 basis to receive nivolumab plus relatlimab and chemotherapy (n = 138) or nivolumab plus chemotherapy (n = 136) until disease progression, unacceptable toxicity, or consent withdrawal. Stratification was based on LAG-3 expression (≥1% or <1%). The primary end point was objective response rate (ORR) in patients with LAG-3 expression ≥1%. Key secondary end points included progression-free survival (PFS), overall survival (OS), and safety. 

At a median follow-up of 11.9 months, in patients with LAG-3 expression ≥1%, ORR was 48% in the relatlimab arm and 61% in the control arm. Median PFS was 7 months in the relatlimab arm and 8.3 months in the control arm. Median OS was 13.5 months and 16 months, respectively. Grade 3/4 treatment-related adverse events occurred in 69% of patients in the relatlimab arm and 61% of patients in the control arm. The most frequent adverse events included neutropenia, fatigue, peripheral neuropathy, diarrhea, and anemia. Treatment discontinuation due to any-grade treatment-related adverse event occurred in 42% of patients in the relatlimab arm and 36% of patients in the control arm. There were 3 treatment-related deaths in the relatlimab arm and 1 treatment-related death in the control arm. 

“The results from the RELATIVITY-060 trial endorse a current standard of care (chemotherapy/anti-PD-1 antibody) as the addition of LAG-3 blockade in untreated upper esophagogastric cancers does not add significant benefit,” added Journal of Clinical Oncology associate editor Eileen M. O’Reilly, MD, Memorial Sloan Kettering Cancer Center, New York, New York. 

“Additional studies may identify subgroups of patients that could benefit from relatlimab-based therapies to treat unresectable, locally advanced or metastatic GC/GEJC,” concluded Dr Hegewisch-Becker et al. 

Source: 

Hegewisch-Becker S, Mendez G, Chao J, et al. First-line nivolumab and relatlimab plus chemotherapy for gastric or gastroesophageal junction adenocarcinoma: The phase II RELATIVITY-060 study. J Clin Oncol. Published online: May 9, 2024. doi: 10.1200/JCO.23.01636