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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03007-5

摘要内容如下：

抗程序性细胞死亡蛋白1（PD-1）治疗和化疗可延长不可切除的晚期或转移性胃腺癌或胃食管交界腺癌（GEJ）患者的生存期。与程序性细胞死亡1配体1（PD-L1）联合阳性评分（CPS）-阳性或CPS-高肿瘤患者相比，PD-L1联合阳性评分（CPS）-阴性或CPS-低肿瘤患者从抗PD-1治疗中获益更多。在这项1B/2期研究中，我们评估了Cadonilimab（一种靶向PD-1和细胞毒性T淋巴细胞抗原-4的双特异性抗体）联合化疗作为一线治疗人表皮生长因子受体2阴性的不可切除的晚期或转移性胃癌或GEJ腺癌患者的疗效和安全性。主要终点是1B期的推荐2期剂量（RP2D）和2期的客观缓解率。次要终点包括疾病控制率、缓解持续时间、缓解时间、无进展生存期、总生存期（OS）和安全性。达到主要终点。在1B期剂量递增期间未观察到剂量限制性毒性；推荐的2期剂量确定为每2周6mgkg-1。客观缓解率为52.1%（95%可信区间（CI）=41.6-62.5），其中完全缓解和部分缓解分别为4.3%和47.9%。中位缓解期、无进展生存期和总生存期分别为13.73个月（95%CI=7.79~19.12）、8.18个月（95%CI=6.67~10.48）和17.48个月（95%CI=12.35~26.55）。PD-L1 CPS≥5的患者的中位OS为20.32个月（95%CI=4.67-无法估计）；在PD-L1 CPS<1的患者中，中位OS达到17.64个月（95%CI=11.63-31.70）。最常见的与治疗相关的3级或更高级别不良事件为中性粒细胞计数减少（19.1%）、血小板计数减少（16.0%）、贫血（12.8%）和白细胞计数减少（8.5%）。未发现新的安全信号。无论PD-L1表达如何，目前的方案在胃癌或GEJ腺癌患者中显示出有希望的临床活性和可控制的安全性。ChinaDrugTrials.org.CN注册：CTR20182027。

英文原文如下：

Abstracts

Treatment with anti-programmed cell death protein 1 (PD-1) therapy and chemotherapy prolongs the survival of patients with unresectable advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The benefit from anti-PD-1 therapy is enriched in patients with programmed cell death 1 ligand 1 (PD-L1) combined positive score (CPS)-positive or CPS-high tumors compared with patients with PD-L1 CPS-negative or CPS-low tumors. In this phase 1b/2 study, we evaluated the efficacy and safety of cadonilimab, a bispecific antibody targeting PD-1 and cytotoxic T-lymphocyte antigen-4, plus chemotherapy as first-line treatment in patients with human epidermal growth factor receptor 2-negative unresectable advanced or metastatic gastric or GEJ adenocarcinoma. The primary endpoint was the recommended phase 2 dose (RP2D) for phase 1b and the objective response rate for phase 2. Secondary endpoints included disease control rate, duration of response, time to response, progression-free survival, overall survival (OS) and safety. The primary endpoint was met. No dose-limiting toxicities were observed during dose escalation in phase 1b; the recommended phase 2 dose was determined as 6 mg kg-1 every 2 weeks. The objective response rate was 52.1% (95% confidence interval (CI) = 41.6-62.5), consisting of complete and partial responses in 4.3% and 47.9% of patients, respectively. The median duration of response, progression-free survival and OS were 13.73 months (95% CI = 7.79-19.12), 8.18 months (95% CI = 6.67-10.48) and 17.48 months (95% CI = 12.35-26.55), respectively. The median OS in patients with a PD-L1 CPS ≥ 5 was 20.32 months (95% CI = 4.67-not estimable); in patients with a PD-L1 CPS < 1, the median OS reached 17.64 months (95% CI = 11.63-31.70). The most common treatment-related grade 3 or higher adverse events were decreased neutrophil count (19.1%), decreased platelet count (16.0%), anemia (12.8%) and decreased leukocyte count (8.5%). No new safety signal was identified. The current regimen showed promising clinical activity and manageable safety in patients with gastric or GEJ adenocarcinoma regardless of PD-L1 expression. Chinadrugtrials.org.cn registration: CTR20182027.

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