We evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint inhibitor-naïve patients with locally advanced/metastatic urothelial carcinoma. TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month progression free rates (PFRs) were 46.4% and 36.5%, respectively. Median OS was not reached; 6-, 12- and 24-month OS rates were 83.3%, 72.2%, and 55.1%, respectively. In post-hoc analysis, patients with a tumor infiltrating CD8+ lymphocyte (CD8+ TIL) count ≥99 and/or programmed cell death protein 1 (PD-L1) Combined Positive Score (CPS) ≥50 and lymphocyte count >1380 cells/μL had higher ORRs and prolonged PFS versus patients with a CD8+ TIL count <99, PD-L1 CPS <50, and lymphocyte count ≤1380 cells/μL. Thirty-four (94.4%) patients receiving combination therapy experienced treatment-related adverse events (AEs), with pyrexia (n=15, 41.7%), injection-site reactions (n=15, 41.7%), injection-site induration (n=6, 16.7%), and malaise (n=6, 16.7%) the most common. No grade ≥3 treatment-related AEs occurred in ≥10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in locally advanced/metastatic urothelial carcinoma.

中文翻译：

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TAS0313 加派姆单抗治疗化疗后免疫检查点抑制剂未使用​​的局部晚期或转移性尿路上皮癌

我们评估了 TAS0313（一种多表位长肽疫苗）联合派姆单抗（pembrolizumab）在化疗后未接受免疫检查点抑制剂治疗的局部晚期/转移性尿路上皮癌患者中的有效性和安全性。皮下注射 TAS0313 9 mg，随后在第 1 天注射 200 mg 派姆单抗，并在第 1 和 2 周期的第 8 和 15 天以及 21 天周期中后续周期的第 1 天作为单一疗法。主要终点是客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）和安全性。评估反应的生物标志物。在入组的 36 名患者中，ORR 为 33.3%（完全缓解：7 名患者；部分缓解：5 名患者）。中位 PFS 为 5.0 个月；6 个月和 12 个月无进展率 (PFR) 分别为 46.4% 和 36.5%。未达到中位 OS；6、12 和 24 个月 OS 率分别为 83.3%、72.2% 和 55.1%。在事后分析中，肿瘤浸润 CD8+ 淋巴细胞 (CD8+ TIL) 计数≥99 和/或程序性细胞死亡蛋白 1 (PD-L1) 综合阳性评分 (CPS) ≥50 且淋巴细胞计数 > 1380 个细胞/μL 的患者与 CD8+ TIL 计数 < 99、PD-L1 CPS < 50 和淋巴细胞计数 ≤ 1380 个细胞/μL 的患者相比，具有更高的 ORR 和延长的 PFS。34 名 (94.4%) 接受联合治疗的患者出现了治疗相关的不良事件 (AE)，包括发热 (n=15, 41.7%)、注射部位反应 (n=15, 41.7%)、注射部位硬结 ( n=6, 16.7%)，而不适 (n=6, 16.7%) 最常见。≥10% 的患者未发生 ≥3 级治疗相关 AE。TAS0313 联合派姆单抗联合疗法在局部晚期/转移性尿路上皮癌中显示出良好的疗效和可控的安全性。