Preliminary results of a phase I dose escalation study of IMM2510, a PD-L1 and VEGF bispecific fusion protein, in patients with advanced tumors.
Authors: Cheng Xiangdong , Song Zhengbo , Zhang Jian , Jin Jianan , Gao Shuiping , Liu Rujiao , Sun Yuping , Zhang Yan , Gao Shegan , Jia Ruinuo , Jing Deqiang , Xu Yu , Zheng Lina , Zhao Xiwen , Li Wei , Lu Qiying , Tian Wenzhi , Hu Xichun 
Published: June 2023

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Background: It is well established that anti-PD-1/PD-L1 and anti-VEGF therapies have excellent synergic effects. Previous clinical trials showed that immunotherapy using anti-PD-1/PD-L1 combined with various VEGF/VERFR targeting agents achieved better efficacy for advanced tumors. IMM2510 is a novel bispecific fusion protein targeting PD-L1 and VEGFs with good efficacy and safety profile verified by our preclinical study. Here we report the preliminary data of an ongoing phase I dose escalation clinical trial of IMM2510 in human. Methods: A phase I, multicenter, open labelled, dose escalation study, was designed to evaluate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of IMM2510. Patients (pts) with advanced solid tumors who had undergone more than two prior lines of PD-1/PD-L1 or antiangiogenic inhibitor therapies were excluded. IMM2510 was administered intravenously Q2W by using accelerated titration (0.007 mg/kg, 0.03 mg/kg) followed by 3+3 dose escalation design (0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, 6.0 mg/kg, and 10.0 mg/kg) to evaluate the safety and to determine recommended phase II dose (RP2D). Anti-tumor activity was evaluated based on RECIST v1.1. Results: As of Dec 15, 2022, 22 pts had received IMM2510 at 8 dose levels (0.007 mg/kg-10.0 mg/kg), the median age was 55.5 yrs, the median prior line of therapy was 3, ranging 1-12. No DLT was observed. The most common TRAEs (≥ 20%) were infusion related reaction (IRR) (63.6%), diarrhea (22.7%), anemia (22.7%). 4 pts experienced G3 TRAEs, including IRR (4.5%), diarrhea (4.5%), pain in extremity (4.5%), C-reactive protein increased (4.5%), procalcitonin increased (4.5%) and lymphocyte count decreased (4.5%). No G4/G5 TRAE occurred. MTD had not been reached. Based on 17 evaluable pts, 1 confirmed PR was observed after 24-week of treatment at 3.0 mg/kg in an ongoing patient with lung squamous cell carcinoma who was IO resistant to prior therapies. Additionally, SDs were seen in 4 patients (1 ovarian serous carcinoma at 0.1 mg/kg, 1 cervical squamous cell carcinoma at 3.0 mg/kg, 1 malignant pleural mesothelioma at 6.0 mg/kg, and 1 breast invasive ductal carcinoma at 10.0 mg/kg). After the cut-off date, another NSCLC patient at 10.0 mg/kg achieved PR after 9-week of treatment and was ongoing on the study. Preliminary PK analysis demonstrated that T1/2 of IMM2510 was around 6 days at the high dose levels. PD data showed that at doses of 3.0 mg/kg or greater, the circulating VEGF-A was completely blocked after first administration till the end of treatment. Conclusions: These data indicated that IMM2510 is well tolerated at the dose levels evaluated, and preliminary anti-tumor efficacy in solid tumors is encouraging. The phase I/II is ongoing. Clinical trial information: chictr20211203 .