METHODS: Patients with unresectable, locally advanced or metastatic GC/GEJC were randomly assigned 1:1 to nivolumab + relatlimab (fixed-dose combination) + chemotherapy or nivolumab + chemotherapy. The primary end point was objective response rate (ORR; per RECIST v1.1 by blinded independent central review [BICR]) in patients whose tumors had LAG-3 expression ≥1%.
RESULTS: Of 274 patients, 138 were randomly assigned to nivolumab + relatlimab + chemotherapy and 136 to nivolumab + chemotherapy. Median follow-up was 11.9 months. In patients with LAG-3 expression ≥1%, BICR-assessed ORR (95% CI) was 48% (38 to 59) in the nivolumab + relatlimab + chemotherapy arm and 61% (51 to 71) in the nivolumab + chemotherapy arm; median progression-free survival (95% CI) by BICR was 7.0 months (5.8 to 8.4) versus 8.3 months (6.9 to 12.1; hazard ratio [HR], 1.41 [95% CI, 0.97 to 2.05]), and median overall survival (95% CI) was 13.5 months (11.9 to 19.1) versus 16.0 months (10.9 to not estimable; HR, 1.04 [95% CI, 0.70 to 1.54]), respectively. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 69% and 61% of all treated patients, and 42% and 36% of patients discontinued because of any-grade TRAEs in the nivolumab + relatlimab + chemotherapy and nivolumab + chemotherapy arms, respectively.
CONCLUSIONS: RELATIVITY-060 did not meet its primary end point of improved ORR in patients with LAG-3 expression ≥1% when relatlimab was added to nivolumab + chemotherapy compared with nivolumab + chemotherapy. Further studies are needed to address whether adding anti-LAG-3 to anti-PD-1 plus chemotherapy can benefit specific GC/GEJC patient subgroups.
方法:不可切除的患者,局部晚期或转移性GC/GEJC以1:1的比例随机分配至nivolumab+relatlimab(固定剂量联合)+化疗或nivolumab+化疗.主要终点是肿瘤LAG-3表达≥1%的患者的客观缓解率(ORR;根据RECISTv1.1,盲法独立中心评价[BICR])。
结果:在274名患者中,138人被随机分配到nivolumab+relatlimab+化疗和136人被随机分配到nivolumab+化疗。中位随访时间为11.9个月。在LAG-3表达≥1%的患者中,BICR评估的ORR(95%CI)在nivolumab+relatlimab+化疗组中为48%(38至59),在nivolumab+化疗组中为61%(51至71);BICR的中位无进展生存期(95%CI)为7.0个月(5.8至8.4)和8.3个月(6.9至12.1;风险比[HR],1.41[95%CI,0.97至2.05]),中位总生存期(95%CI)为13.5个月(11.9至19.1)与16.0个月(10.9至不可估计;HR,1.04[95%CI,0.70至1.54]),分别。3级或4级治疗相关不良事件(TRAEs)发生在69%和61%的所有接受治疗的患者。42%和36%的患者因任何级别的TRAE在nivolumab+relatlimab+化疗和nivolumab+化疗组停药,分别。
结论:与nivolumab+化疗相比,在LAG-3表达≥1%的患者中,RELITIVITY-060未达到ORR改善的主要终点。需要进一步的研究来解决将抗LAG-3添加到抗PD-1加化疗是否可以使特定的GC/GEJC患者亚组受益。