Monalizumab联用对3期NSCLC的效果对比

COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non–Small-Cell Lung Cancer

（IF, JCO., 44.544）

PURPOSE 目的

Durvalumab significantly improves overall survival for patients with unresectable stage III non–smallcell lung cancer and no progression after concurrent chemoradiotherapy (cCRT). Building upon that standard of care, COAST is a phase II study of durvalumab alone or combined with the anti-CD73 monoclonal antibody oleclumab or anti-NKG2A monoclonal antibody monalizumab as consolidation therapy in this setting.

德瓦鲁单抗显著提高了不可切除的III期非小细胞肺癌，在同步放化疗（cCRT）后无进展患者的总体生存率。在该护理标准的基础上，COAST正在进行一项II期研究，将德瓦鲁单抗单独使用或与抗CD73单克隆抗体oleclumab或抗NKG2A单克隆抗体monalizumab联合作为巩固治疗。

METHODS 方法

Patients with unresectable stage III non–small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and no progression after cCRT were randomly assigned 1:1:1, # 42 days post-cCRT, to durvalumab alone or combined with oleclumab or monalizumab for up to 12 months, stratified by histology. The primary end point was investigator-assessed confirmed objective response rate (ORR; RECIST v1.1).

患有不可切除的III期非小细胞肺癌、东部肿瘤协作组体能状态为0/1且cCRT后无进展的患者，在cCRT后42天以1:1:1的比例被随机分配到单用德瓦鲁单抗、或与oleclumab或monalizumab联合使用12个月，按组织学分层。主要终点是研究者评估的确认客观缓解率（ORR；RECIST v1.1）。

RESULTS 结果

Between January 2019 and July 2020, 189 patients were randomly assigned. At this interim analysis (data cutoff, May 17, 2021), median follow-up was 11.5 months (range, 0.4-23.4 months; all patients). Confirmed ORR was numerically higher with durvalumab plus oleclumab (30.0%; 95% CI, 18.8 to 43.2) and durvalumab plus monalizumab (35.5%; 95% CI, 23.7 to 48.7) versus durvalumab (17.9%; 95% CI, 9.6 to 29.2). Progression-free survival (PFS) was prolonged with both combinations versus durvalumab (plus oleclumab: hazard ratio, 0.44; 95% CI, 0.26 to 0.75; and plus monalizumab: hazard ratio, 0.42; 95% CI, 0.24 to 0.72), with higher 12-month PFS rates (plus oleclumab: 62.6% [95% CI, 48.1 to 74.2] and plus monalizumab: 72.7% [95% CI, 58.8 to 82.6] v durvalumab alone: 33.9% [95% CI, 21.2 to 47.1]). All-cause grade $ 3 treatmentemergent adverse events occurred in 40.7%, 27.9%, and 39.4% with durvalumab plus oleclumab, durvalumab plus monalizumab, and durvalumab, respectively.

2019年1月至2020年7月期间， 189名患者被随机分配。在本次中期分析中（数据截止，2021年5月17日），中位随访时间为11.5个月（范围，0.4-23.4个月；所有患者）。与单用德瓦鲁单抗（17.9%；95% CI，9.6-29.2）相比，德瓦鲁单抗联合oleclumab（30.0%；95% CI，18.8-43.2）和德瓦鲁单抗联合monalizumab（35.5%；95% CI，23.7-48.7）的确认的ORR数值更高。与单用德瓦鲁单抗相比，两种联合用药的无进展生存期（PFS）均有延长（联合oleclumab：风险比，0.44；95% CI，0.26至0.75；联合monalizumab：风险比，0.42；95% CI，0.24至0.72），12个月的PFS率更高（联合oleclumab：62.6% [95% CI，48.1至74.2]，联合monalizumab：72.7% [95% CI，58.8至82.6]，相比单用德瓦鲁单抗：33.9% [95% CI，21.2至47.1]）。德瓦鲁单抗联合oleclumab、德瓦鲁单抗联合 monalizumab和德瓦鲁单抗单药的全因3级治疗紧急不良事件发生率分别为40.7%、27.9%和39.4%。

CONCLUSION 结论

Both combinations increased ORR and prolonged PFS versus durvalumab alone. Safety was similar across arms with no new or significant safety signals identified with either combination. These data support their further evaluation in a phase III trial.

与单用德瓦鲁单抗相比，两种联合用药均增加了ORR，并延长了PFS。两种组合的安全性相似，均未发现新的或重要的安全信号。这些数据得以支持他们在III期试验中的进一步评估。