A phase I study evaluating IMM2520 (CD47/PD-L1 bispecific molecule) in pts with advanced solid tumor

BackgroundIMM2520 consists of a PD-L1 antibody with an engineered ADCC-enhanced IgG1 Fc region, linked to the domain of SIRPα at the N-terminus of heavy chains. Blockade of PD-L1 and CD47- SIRPα pathway fully activate macrophages and induce enhanced ADCP and ADCC activity, leading to potent integrated antitumor response.MethodsThis is an open-label, first in human, dose escalation and dose expansion phase1 study to evaluate the safety, RP2D/MTD and anti-tumor effect for IMM2520 in pts with advanced solid tumor. The dose escalation was designed with an accelerated titration at first dose level followed by standard 3+3 design. IMM2520 was administered weekly in a 28 day-cycle. Additional patients will be enrolled for potential RP2D to identify optimized dose level. Here we report results in ongoing dose escalation stage.ResultsAs of 4 Apr 2024, 18 patients (pts) were treated at 5 dose levels (from 0.1mpk to 4mpk). Most pts (61%) previously received ≥ 3 lines of systemic anti-tumor therapy, including 9 (50%) pts with PD-(L)1 therapy history. No DLTs were observed yet. All pts reported treatment-related adverse event (TRAE), of which 10 (56%) pts were ≥ Grade 3. The most common TRAE of any grade was platelet decreased (89%), anemia (67%), white blood cell decreased (56%) and infusion-related reaction (IRR) (56%). The most common TRAE of ≥ Grade 3 was lymphocyte decreased (50%), platelet decreased (33%) and anorexia (5.6%). No AE leading to treatment discontinuation was observed. Of 11 efficacy evaluable pts,1 unconfirmed partial response (PR) in small cell lung cancer (SCLC) at 2mpk (with 2 previous lines of therapy including immunotherapy and negative PD-L1 expression) and 5 stable disease (SD) were observed, including 1 cervical cancer with 21.1% tumor shrinkage and 1 colorectal cancer with 11.1% tumor shrinkage. Pharmacodynamic biomarker included CD47 Target occupancy (TO) on peripheral circulating CD3+T cells using flow cytometry analysis. The rate of CD47 TO was mild and exhibits a dose-dependent trend.ConclusionsIMM2520 showed tolerance at the evaluated doses and preliminary anti-tumor activity in advanced solid tumor, especially for SCLC. The dose escalation is ongoing.Clinical trial identificationNCT05780307.Legal entity responsible for the studyImmuneOnco BioPharmaceuticals (Shanghai) Inc.FundingImmuneOnco BioPharmaceuticals (Shanghai) Inc.DisclosureA. Wu, X. Zhao, Z. Wang, Q. Lu: Financial Interests, Personal, Full or part-time Employment: ImmuneOnco BioPharmaceuticals (Shanghai) Inc. W. Tian: Financial Interests, Personal, Stocks or ownership: ImmuneOnco BioPharmaceuticals (Shanghai) Inc. All other authors have declared no conflicts of interest.