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Abstract：
Immune checkpoint inhibitors are the leading approaches in tumor immunotherapy. The aim of the study was to establish recommended phase 2 doses (RP2Ds) of intravenous cetrelimab, a checkpoint inhibitor, alone and with oral erdafitinib in Japanese patients with advanced solid tumors. This open-label, non-randomized, dose-escalation phase 1/1b study enrolled adults with advanced solid tumors who were ineligible for standard therapy. Study was conducted in two parts: phase 1a assessed cetrelimab at three dosing levels (80 mg every 2 weeks [Q2W], 240 mg Q2W, and 480 mg Q4W); phase 1b assessed cetrelimab+erdafitinib at two dosing levels (240 mg Q2W + 6 mg once daily [QD] and 240 mg Q2W + 8 mg QD). Primary endpoint was frequency and severity of dose-limiting toxicities (DLTs) of cetrelimab ± erdafitinib. In total 22 patients (phase 1a, n = 9; phase 1b, n = 13) were enrolled. Median duration of follow-up was 8.64 months in phase 1a and 2.33 months in phase 1b. In phase 1a, DLTs weren\'t reported while in phase 1b, 1 patient who received 240 mg cetrelimab + 6 mg erdafitinib reported Stevens-Johnson syndrome (grade 3, immune-related). Overall, 88.9% patients in phase 1a (grade ≥ 3: 44.4%) and 100.0% in phase 1b (grade ≥ 3: 53.8%) experienced ≥ 1 treatment-related adverse events (TEAEs); 33.3% in phase 1a and 38.5% in phase 1b reported serious TEAEs, of which 11.1% patients in phase 1a and 15.4% in phase 1b had TEAEs which led to treatment discontinuation. Cetrelimab alone and in combination with erdafitinib showed manageable safety in Japanese patients with advanced solid tumors. RP2Ds were determined as 480 mg cetrelimab Q4W for monotherapy, and cetrelimab 240 mg Q2W + erdafitinib 8 mg QD for combination therapy.
摘要：
免疫检查点抑制剂是肿瘤免疫治疗的主要方法。该研究的目的是建立推荐的2期剂量（RP2Ds）的静脉注射西特瑞马，检查点抑制剂,单独和口服erdafitinib治疗日本晚期实体瘤患者。这个开放标签，非随机化，剂量递增1/1b期研究纳入了不符合标准治疗条件的晚期实体瘤成人.研究分两个部分进行：1a期评估西特瑞马在三个剂量水平（80毫克每2周[Q2W]，240毫克Q2W，和480mgQ4W）；1b期评估了两种给药水平（240mgQ2W+6mg每日一次[QD]和240mgQ2W+8mgQD）的西曲瑞马+厄达替尼。主要终点是西特瑞马±erdafitinib的剂量限制性毒性（DLTs）的频率和严重程度。总共22名患者(第1a期，n=9；阶段1b，n=13）。1a期的中位随访时间为8.64个月，1b期为2.33个月。在阶段1a，在1b阶段没有报告DLT，1例接受240mg西特瑞马+6mgerdafitinib的患者报告了Stevens-Johnson综合征（3级，免疫相关）。总的来说,在1a期（≥3级：44.4%）和1b期（≥3级：53.8%）分别有88.9%和100.0%的患者经历了≥1次治疗相关不良事件（TEAEs）；1a期有33.3%和1b期有38.5%的患者报告了严重的TEAEs。其中11.1％的1a期患者和15.4％的1b期患者出现TEAE，导致治疗中止。在日本晚期实体瘤患者中，西特瑞马单独和与erdafitinib联合使用显示出可控的安全性。RP2Ds被确定为480mg西特雷单抗Q4W用于单一疗法，西特瑞马240mgQ2W+erdafitinib8mgQD用于联合治疗。
