PDF(Pubmed)
Abstract：
OBJECTIVE: Open-label phase II study (RELATIVITY-060) to investigate the efficacy and safety of first-line nivolumab, a PD-1-blocking antibody, plus relatlimab, a lymphocyte-activation gene 3 (LAG-3)-blocking antibody, plus chemotherapy in patients with previously untreated advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC).
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.
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.
摘要：
目的：开放标签II期研究（RELATIVITY-060）研究一线纳武单抗的疗效和安全性，PD-1阻断抗体，加上relatlimab,淋巴细胞激活基因3（LAG-3）阻断抗体，先前未经治疗的晚期胃癌（GC）或胃食管结合部癌（GEJC）患者加化疗。
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。
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。
