In the phase II RELATIVITY-060 study, results of which were reported in the Journal of Clinical Oncology, Susanna Hegewisch-Becker, MD, PhD, and colleagues found that the addition of the LAG-3–blocking antibody relatlimab to first-line nivolumab plus chemotherapy did not improve the objective response rate in patients with locally advanced, unresectable, or metastatic gastric or gastroesophageal junction adenocarcinoma with tumor LAG-3 expression of ≥ 1%.
Susanna Hegewisch-Becker, MD, PhD
Study Details
In the open-label trial, 274 patients from sites in 17countries were randomly assigned between October 2018 and November 2019 to receive either a fixed-dose combination of nivolumab at 360 mg and relatlimab at 120 mg plus investigator’s choice of oxaliplatin-based chemotherapy (relatlimab group, n = 138) or nivolumab plus chemotherapy (control group, n = 136). Of these, 97 patients (70%) in the relatlimab group and 98 (72%) in the control group had tumor LAG-3 expression of ≥ 1%. The primary endpoint of the study was objective response rate on blinded independent central review in patients with tumor LAG-3 expression of ≥ 1%.
Key Findings
Median follow-up was 11.9 months.
Among the 97 vs 98 patients with LAG-3 expression of ≥ 1%, objective response rates were 48% (95% confidence interval [CI] = 38%–59%) in the relatlimab group vs 61% (95% CI = 51%–71%) in the control group (P = .0711). Medan response duration was 5.7 months (95% CI = 4.4–10.0 months) vs 10.1 months (95% CI = 6.4–13.3 months).
Among patients with LAG-3 expression of ≥ 1%, median progression-free survival was 7.0 months (95% CI = 5.8–8.4 months) in the relatlimab group vs 8.3 months (95% CI = 6.9–12.1 months) in the control group (hazard ratio [HR] = 1.41, 95% CI = 0.97–2.05). Median overall survival was 13.5 months (95% CI = 11.9–19.1 months) vs 16.0 months (95% CI = 10.9 months to not estimable; HR = 1.04, 95% CI = 0.70–1.54), respectively.
Among all patients, grade 3 or 4 treatment-related adverse events occurred in 69% of patients in the relatlimab group vs 61% in the control group. Serious treatment-related adverse events occurred in 38% vs 28%. Treatment-related adverse events led to treatment discontinuation in 42% vs 36%. Treatment-related fatal adverse events occurred in three patients in the relatlimab group (autoimmune encephalitis, lung infection, and acute renal failure) and one patient in the control group (acute renal insufficiency).
The investigators concluded, “RELATIVITY-060 did not meet its primary endpoint of improved objective response rate in patients with LAG-3 expression of ≥ 1% when relatlimab was added to nivolumab plus chemotherapy compared with nivolumab plus chemotherapy. Further studies are needed to address whether adding anti–LAG-3 [agents] to anti–PD-1 [agents] plus chemotherapy can benefit specific gastric or gastroesophageal junction adenocarcinoma patient subgroups.”
Dr. Hegewisch-Becker, of Hematology-Oncology Practice Eppendorf (HOPE), Hamburg, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
