[Translation] An open-label, multicenter, first-in-human, dose-escalation and dose-expansion Phase I clinical study to evaluate IMM40H in the treatment of advanced solid tumors and relapsed or refractory hematological malignancies

主要目的 1.初步评价IMM40H在人体的安全性和耐受性； 2.确定IMM40H在人体的最大耐受剂量（MTD）和II期推荐剂量（RP2D）； 3.初步评价IMM40H的抗肿瘤活性或初步疗效。次要目的 1.评价IMM40H在人体的药代动力学（PK）/药效动力学（PD）特征； 2.评价IMM40H在人体的免疫原性。探索性目的 1.探索IMM40H的人体暴露量和应答（E-R）的关系； 2.探索IMM40H的群体药代动力学（pop-PK）特征；

[Translation]

Main purpose 1. Preliminary evaluation of the safety and tolerability of IMM40H in humans; 2. Determine the maximum tolerated dose (MTD) and phase II recommended dose (RP2D) of IMM40H in humans; 3. Preliminary evaluation of the anti-tumor activity or preliminary efficacy of IMM40H. Secondary purpose 1. Evaluate the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of IMM40H in humans; 2. Evaluate the immunogenicity of IMM40H in humans. Exploratory purpose 1. Explore the relationship between human exposure and response (E-R) of IMM40H; 2. Explore the population pharmacokinetic (pop-PK) characteristics of IMM40H;

Start Date-

Sponsor / Collaborator

ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup

NCT05549557 / Not yet recruitingPhase 1

An Open-label, Multi-center Phase I Clinical Study of IMM40H in Patients With Advanced Solid Tumor and Hematological Malignancies

This is first-in-human, open-label, multi-center, dose-escalation (phase Ia) and cohort expansion (phase Ib) phase I study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic, immunogenicity, and antitumor activities of IMM40H in patients with advanced malignancies including solid tumor and hematological malignancies.

Start Date01 Sep 2022

Sponsor / Collaborator

ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup

100 Clinical Results associated with IMM-40H

100 Translational Medicine associated with IMM-40H

100 Patents (Medical) associated with IMM-40H

Literatures (Medical) associated with IMM-40H

01 Jan 2023·Frontiers in oncology

The novel high-affinity humanized antibody IMM40H targets CD70, eliminates tumors via Fc-mediated effector functions, and interrupts CD70/CD27 signaling.

Article

Author: Yang, Chunmei ; Bai, Xing ; Zhang, Fan ; Zhao, Gui ; Tian, Wenzhi ; Chen, Dianze ; Sun, Nana ; Peng, Liang ; Liu, Dandan ; Zhang, Wei ; Tu, Xiaoping ; Zhang, Ruliang ; Guo, Huiqin ; Wang, Tianxiang ; Li, Song ; Yang, Yanan ; Zhang, Li

BackgroundA significant level of CD70 can be detected in various types of tumor tissues and CD27 is expressed on Treg cells, but CD70 expression is low in normal tissues. The interaction between CD70 and CD27 can stimulate the proliferation and survival of cancer cells and increase the level of soluble CD27, which is associated with poor prognosis in patients with lymphoma and certain solid tumors. Thus, it is a promising therapeutic target for the treatment of many major CD70+ cancer indications, including CD70+ lymphoma, RCC, NSCLC, HNSCC and OC.MethodsIMM40H was obtained through hybridoma screening and antibody humanization techniques. IMM40H was evaluated for its binding, blocking, Fc-dependent effector functions and antitumor activity characteristics in various in vitro and in vivo systems. The safety and tolerability profile of IMM40H were evaluated through single and repeated administration in cynomolgus monkeys.ResultsIn vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively. IMM40H also exhibited potent Fc-dependent effector functions (ADCC/CDC/ADCP), and could make a strong immune attack on tumor cells and enhance therapeutic efficacy. Preclinical findings showed that IMM40H had potent antitumor activity in multiple myeloma U266B1 xenograft model, and could eradicate subcutaneously established tumors at a low dose of 0.3 mg/kg. IMM40H (0.3 mg/kg) showed therapeutic effects faster than cusatuzumab (1 mg/kg). A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt's lymphoma Raji and renal carcinoma cell A498 tumor models. In cynomolgus monkeys, the highest non-severely toxic dose (HNSTD) for repeat-dose toxicity was up to 30 mg/kg, while the maximum tolerated dose (MTD) for single-dose toxicity was up to 100 mg/kg, confirming that IMM40H had a good safety and tolerability profile.ConclusionIMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling.

100 Deals associated with IMM-40H

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	-	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	01 Sep 2022
Hematologic Neoplasms	Phase 1	-	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	01 Sep 2022
Solid tumor	Preclinical	US	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	-

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