PO.CTP01.01 · 进行中的临床试验
CVL006联合治疗在晚期实体瘤中的I/II期临床试验
Phase I/II clinical trial of CVL006 combination therapy in advanced solid tumors
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：CVL006是一种新型双特异性抗体，旨在通过同时阻断两条机制上不同的通路——VEGF/VEGFR信号通路和PD-L1/PD-1轴——实现协同抗肿瘤活性。在这项CVL006联合培美曲塞和卡铂、或SKB264、或DS8201、或Enfortumab Vedotin的I/II期临床研究中，将在成人晚期实体瘤受试者中评估安全性、药代动力学（PK）和初步疗效，从而确定推荐II期剂量（RP2D）（NCT07157956）。
方法：这是一项多中心、开放标签、I/II期剂量递增和剂量优化临床研究。I期剂量递增涉及CVL006在四个队列联合治疗中的剂量递增：臂1.1，CVL006联合培美曲塞加卡铂；臂1.2，CVL006联合SKB264；臂1.3，CVL006联合DS-8201a；臂1.4，CVL006联合Enfortumab Vedotin。培美曲塞加卡铂、SKB264、DS-8201a和Enfortumab Vedotin以固定剂量给药，所有队列均采用“3+3”设计进行剂量递增。含9个臂的II期剂量优化研究：进一步评估CVL006联合培美曲塞加卡铂、SKB264、DS-8201a或Enfortumab Vedotin的抗肿瘤活性。患者将接受持续治疗，直至疾病进展（每8周评估一次）、自愿撤回同意、无法耐受的毒性或研究者判定退出研究。
结果：截至2025年12月9日的数据截止日期，6名晚期肿瘤受试者在I期入组并接受10 mg/kg的CVL006，臂1.1有3名受试者，臂1.2有3名受试者。I期结果显示CVL006联合培美曲塞和卡铂、或SKB264耐受性良好，尚未达到MTD。在臂1.1，CVL006治疗相关不良事件（TRAE）的发生率为66.7%（2/3），均为1级，无DLT且无≥2级AE；在臂1.2，CVL006治疗相关不良事件（TRAE）的发生率为100%（3/3），大多为1级，无DLT且无≥3级AE。所有这些AE经对症治疗后均已恢复。在10 mg/kg剂量组，CVL006未出现ADA阳性。臂1.2（N=3）中2名受试者至少进行了一次疗效评估，1例部分缓解（PR），1例疾病稳定（SD）（肿瘤缩小28.57%），ORR为33%，DCR为66.7%。
结论：CVL006联合培美曲塞和卡铂、或SKB264在晚期实体瘤患者中似乎具有良好耐受性并有令人鼓舞的初步疗效，值得进一步研究。
查看英文原文 English abstract
Background: CVL006 is a novel bispecific antibody designed for synergic antitumor activity by simultaneously blocking two mechanistically distinct pathways VEGF/VEGFR signaling and the PD-L1/PD-1 axis. In this phase I/II Clinical Study of CVL006 combo with pemetrexed and carboplatin, or SKB264, or DS8201, or Enfortumab Vedotin, Safety, pharmacokinetics (PK) and preliminary efficacy will be assessed in adult subjects with advanced solid tumors, and, thus, the recommended phase II dose (RP2D) will be established (NCT07157956).
Methods: This is a multicenter, open-label, phase I/II dose-escalation and dose-optimization clinical study. Phase I dose-escalation involves dose escalation of CVL006 in combination therapy across four cohorts: Arm 1.1, CVL006 combined with Pemetrexed plus Carboplatin; Arm 1.2, CVL006 combined with SKB264; Arm 1.3, CVL006 combined with DS-8201a; and Arm 1.4, CVL006 combined with Enfortumab Vedotin. Pemetrexed plus Carboplatin, SKB264, DS-8201a, and Enfortumab Vedotin are administered at fixed doses, and all cohorts utilize a "3+3" design for dose escalation. Phase II Dose-Optimization Study with 9 Arms: To further evaluate anti-tumor activity of CVL006 in combination with Pemetrexed plus Carboplatin, SKB264, DS-8201a, or Enfortumab Vedotin. Patients will receive continuous treatment until disease progression(assessments every 8 weeks), voluntary withdrawal of consent, intolerable toxicity, or investigator-determined withdrawal from the study.
Results: As of the data cutoff date of December 9, 2025, 6 subjects with advanced tumors were enrolled in phase I received CVL006 at 10 mg/kg, 3 subjects in Arm 1.1, 3 subjects in Arm 1.2. Phase I results show that CVL006 combo with pemetrexed and carboplatin, or SKB264 is well-tolerate, MTD has not reached. In Arm 1.1, The incidence of CVL006 treatment-related AEs(TRAEs)was 66.7% (2/3), all Grade 1, no DLT and no ≥ Grade 2 AEs; In Arm 1.2, The incidence of CVL006 treatment-related AEs(TRAEs)was 100% (3/3), most were Grade 1, no DLT and no ≥ Grade 3 AEs. All these AEs were recovered after symptomatic treatment. In the 10 mg/kg dose group, CVL006 showed no incidence of ADA positivity.2 subjects had at least one efficacy assessment in Arm 1.2 (N=3), 1 partial response (PR), 1 stable disease (SD) (tumor shrinkage of 28.57%) , with an ORR of 33% and DCR of 66.7%.
Conclusion: CVL006 combo with pemetrexed and carboplatin, or SKB264 appeared to be well tolerated and had encouraging preliminary efficacy in patients with advanced solid tumors, warranting further investigation.
利益披露 Disclosure
S. Shen, None..
L. Zhang, None..
W. Fang, None.