[Translation] A Phase Ia clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of IMB071703 injection in patients with recurrent or metastatic advanced malignant solid tumors
IMB071703注射液由北京免疫方舟医药科技有限公司自主研发的重组双功能抗体融合蛋白,是一款针对肿瘤微环境的免疫激活剂,分别靶向CD137(4-1BB)和CD40。其可与APC表面的CD40受体结合,活化 CD40信号通路;与T细胞表面的CD137受体结合,活化4-1BB信号通路,同时衔接 APC与T细胞,促进特异性T细胞的增殖与活化。基于FcγR结合缺陷的方法,减少副作用,但保留较高的活化DC和T细胞的抗肿瘤活性。
主要目的:
评估其治疗复发或转移的晚期恶性实体瘤受试者的安全性和耐受性;
确定MTD和/或RP2D;
次要目的:
评估其治疗复发或转移的晚期恶性实体瘤受试者的PK特征;
评估其治疗复发或转移的晚期恶性实体瘤受试者的免疫原性;
采用RECIST V1.1评估其在复发或转移的晚期恶性实体瘤受试者的初步抗肿瘤活性。
探索性目的:
采用iRECIST评估其在复发或转移的晚期恶性实体瘤受试者的初步抗肿瘤活性(仅RECIST V1.1评价为PD后采用iRECIST评价);
评估其治疗复发或转移的晚期恶性实体瘤受试者的PD特征。
[Translation] IMB071703 injection is a recombinant bifunctional antibody fusion protein independently developed by Beijing Immune Ark Pharmaceutical Technology Co., Ltd. It is an immune activator for the tumor microenvironment, targeting CD137 (4-1BB) and CD40 respectively. It can bind to the CD40 receptor on the surface of APC to activate the CD40 signaling pathway; bind to the CD137 receptor on the surface of T cells to activate the 4-1BB signaling pathway, while connecting APC and T cells to promote the proliferation and activation of specific T cells. Based on the FcγR binding defect method, it reduces side effects but retains a high anti-tumor activity of activated DCs and T cells.
Main purpose:
To evaluate its safety and tolerability in the treatment of subjects with recurrent or metastatic advanced malignant solid tumors;
To determine the MTD and/or RP2D;
Secondary purpose:
To evaluate its PK characteristics in the treatment of subjects with recurrent or metastatic advanced malignant solid tumors;
To evaluate its immunogenicity in the treatment of subjects with recurrent or metastatic advanced malignant solid tumors;
To evaluate its preliminary anti-tumor activity in subjects with recurrent or metastatic advanced malignant solid tumors using RECIST V1.1.
Exploratory purpose:
Use iRECIST to evaluate its preliminary anti-tumor activity in subjects with recurrent or metastatic advanced malignant solid tumors (iRECIST evaluation is used only after RECIST V1.1 evaluation of PD);
Evaluate its PD characteristics in subjects with recurrent or metastatic advanced malignant solid tumors.