This study is to evaluate a novel cytotoxic anti-PD-L1, IUAb190708, for the treatment of tumor
PD-L1 is universally expressed in various types of tumors and an important immune down-regulation factor in tumor microenvironment. Application of PD-L1 to cancer therapy is based on the inhibitory mechanism of the PD-L1/PD-1 pathway on T cell function, and as a result, PD-L1 blocking antibodies are developed, IUAb190708 is a humanized monoclonal immunoglobulin G1 κ subclass (IgG1) antibody that specifically recognizes PD-L1 (also known as CD274). Different from known PD-L1 blocking antibodies, i.e., they block the interaction of PD-L1 with PD-1 that recovers T cell function leading to indirect killing of tumor. Whereas IUAb190708 is to induce antibody dependent cell-mediated cytotoxicity (ADCC), i.e., it activates NK cells leading to direct killing of tumor. IUAB190708 can be used as a monotherapy or in combination with other immunotherapies, chemotherapy, and radiation to improve the efficacy of tumor treatment. In the open-label Phase I study, safety, tolerance, pharmacokinetics and activity of IUAb190708 in subjects with advanced or recurrent solid tumors will be evaluated, and MTD, DLT, and RP2D of IUAb190708 will be determined, and eligible subjects will be administered with IUAb190708 at different doses via intravenous infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
90
a novel cytotoxic anti-PD-L1 antibody
Fujian Cancer Hospital
Fuzhou, Fujian, China
RECRUITINGAnyang tumor hospital
Anyang, Henan, China
RECRUITINGCancer hospital of Shandong First Medical University
Jinan, Shandong, China
ORR
Objective response rate (ORR), defined as the number of subjects with complete response (CR) or partial response (PR) divided by the number of subjects in the population of interest.
Time frame: 2 years
DOR
Duration of Objective Response (DOR), defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first.
Time frame: 2 years
PFS
Progressive free survival (PFS), defined as the time between date of first dose of study therapy and date of progression or death, whichever occurs first.
Time frame: 2 years
OS
Overall survival (OS), defined as the time between the date of first dose of study therapy and the date of death.
Time frame: 2 years
Incidence and severity of adverse events (AEs)
Severity is determined based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE Version 5.0)
Time frame: 2 years
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Fudan University Shanghai cancer center
Shanghai, China
RECRUITINGShanghai Pulmonary hospital
Shanghai, China
RECRUITINGShanghai Xinhua hospital
Shanghai, China
RECRUITING