BC001 是一种新型的人源化 IgG1 单克隆抗体，靶向血管内皮生长因子受体-2，用于治疗晚期实体瘤的 I 期临床研究。
Phase I study of BC001, a novel fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2, in advanced solid tumors.
机构信息
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Early Drug Development Center, Peking University Cancer Hospital & Institute, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology/Early Drug Development Center, Peking University Cancer Hospital & Institute, Beijing, China.
出版信息
Cancer Med. 2024 Nov;13(22):e70208. doi: 10.1002/cam4.70208.
BACKGROUND
BC001 is a novel fully human immunoglobulin G1 monoclonal antibody blocking VEGFR2. This phase I study aimed to assess BC001 alone and plus chemotherapy in solid tumors.
METHODS
In dose escalation part, BC001 was assessed at dose levels of 2, 4, 8, 12, 16 mg/kg on day 1,15, every 28 days, followed an accelerated titration and "3 + 3" design. BC001 plus paclitaxel was assessed at dose level of 8, 10 mg/kg. The primary endpoints included the DLT, MTD and RDE of BC001. In dose expansion part, it aimed to assess the anti-tumor activity of BC001 alone and plus chemotherapy in gastric cancer as 2nd line treatment.
RESULTS
Overall, 53 patients were finally enrolled in this study (phase Ia, n = 28; phase Ib, n = 25). In phase Ia part, 1 DLT (grade 4 neutropenia lasting 4 days) was observed in BC001(8 mg/kg) plus paclitaxel cohort. MTD was not reached. All patients experienced TEAEs of any grade. Twenty-four of them suffered ≥ grade 3 TEAEs. leukopenia (n = 33, 62.3%), hemoglobin decreased (n = 32, 60.4%), neutropenia (n = 29, 54.7%) were commonly observed hematological toxicities. The half-life of 140-240 h. And the PK parameters were not largely influenced by combination with paclitaxel. The serum sVEGFR-1, VEGF-A, sVEGFR-2 could not predict the efficacy. Based on the safety, PK and efficacy data, BC001 of 8 mg/kg was determined as RED. Among the GC patients(n = 21) who receiving BC001 plus paclitaxel as 2nd-line treatment in phase 1b part, 6 patients achieved PR and 10 patients experienced SD. The ORR was 28.6% (95% CI 11.3%, 52.2%) and the DCR was 76.2% (95% CI 52.8%, 91.8%), with the median PFS of 5.4 months (95% CI 1.9, 7.0) and OS of 9.4 months (95% CI 5.4, NA). The median DoR was 5.1 months (95% CI 2.6, NA).
CONCLUSIONS
BC001 showed acceptable safety profile and preliminary response in both single-agent and combination with chemotherapy cohorts, especially in GC.
背景
BC001 是一种新型的全人源 IgG1 单克隆抗体，可阻断 VEGFR2。这项 I 期研究旨在评估 BC001 单药治疗和联合化疗治疗实体瘤的疗效。
方法
在剂量递增部分，BC001 以 2、4、8、12、16mg/kg 的剂量于第 1 天和第 15 天给药，每 28 天一次，随后进行加速滴定和“3+3”设计。BC001 联合紫杉醇的剂量水平为 8、10mg/kg。主要终点包括 BC001 的 DLT、MTD 和 RDE。在剂量扩展部分，旨在评估 BC001 单药和联合化疗作为二线治疗胃癌的抗肿瘤活性。
结果
共有 53 名患者最终入组本研究（I 期 a 部分，n=28；I 期 b 部分，n=25）。在 I 期 a 部分，BC001（8mg/kg）联合紫杉醇组观察到 1 例 DLT（持续 4 天的 4 级中性粒细胞减少症）。未达到 MTD。所有患者均出现任何级别的治疗相关不良事件。其中 24 例患者发生≥3 级治疗相关不良事件。常见的血液学毒性包括白细胞减少（n=33，62.3%）、血红蛋白降低（n=32，60.4%）、中性粒细胞减少（n=29，54.7%）。半衰期为 140-240 小时。PK 参数受与紫杉醇联合使用的影响不大。血清 sVEGFR-1、VEGF-A、sVEGFR-2 不能预测疗效。基于安全性、PK 和疗效数据，确定 BC001 的 RED 剂量为 8mg/kg。在 I 期 b 部分接受 BC001 联合紫杉醇二线治疗的 GC 患者（n=21）中，6 例患者达到 PR，10 例患者达到 SD。ORR 为 28.6%（95%CI，11.3%，52.2%），DCR 为 76.2%（95%CI，52.8%，91.8%），中位无进展生存期（PFS）为 5.4 个月（95%CI，1.9，7.0），总生存期（OS）为 9.4 个月（95%CI，5.4，NA）。中位缓解持续时间（DoR）为 5.1 个月（95%CI，2.6，NA）。
结论
BC001 单药及联合化疗均显示出可接受的安全性和初步疗效，特别是在 GC 患者中。
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