A phase 1/2 study to evaluate the efficacy and safety of HB0025 monotherapy for patients (pts) with advanced renal cell carcinoma (RCC).
Authors: Yuan-Yuan Qu, Dingwei Ye, Xiaojie Bian, Weiqing Han, Kan Liu, Tao Dai, Yuping Sun, Jiasheng Bian, Qi Dang, Meili Sun, Zhen Wang, Jian Zhang, Huan Zhou, Zhenyuan Gao, Xiangyang Zhu, Yongmin Yang, Juan Chen, Yang Yang, Junning Wang, Ye Cai
Journal: Journal of Clinical Oncology (2024)

e14503 Background: HB0025 is a recombinant humanized bispecific molecule built on IgG1 that targets the human programmed death ligand 1 (PD-L1) (CD274) and vascular endothelial growth factor (VEGF, VEGF-A, VEGF165). In phase Ia, HB0025 monotherapy showed encouraging anti-tumor activity and safety profile in solid tumor. Herein, we aimed to explore safety and efficacy of HB0025 in advanced renal cell carcinoma pts that failed standard treatments. Methods: This ongoing, open-label, multicenter, phase 1/2 trial to evaluate the efficacy and safety of HB0025 monotherapy with 10mg/kg iv q2w for RCC pts. Response was evaluated by RECIST v.1.1 every 8 weeks. The primary endpoint was objective response-rate (ORR). Secondary endpoints included safety (CTCAE v.5.0), disease control rate (DCR), and progression free survival (PFS). Results: As of Dec 25, 2023, 17 (16M/1F) pts were enrolled and all received treatment. Median age was 58 y and 53% pts had intermediate/poor IMDC risk.6 pts were on treatment at data cutoff date. All pts had stage IV disease. 14 (82%) pts were clear cell renal cell carcinoma and the maximum duration of treatment was 7 months. 10 (59%) pts received ≥2 lines of previous systemic therapies and median follow up was 5.1 months. Among total the 15 pts having imaging tumor assessment by RECIST v1.1, 2 achieved partial responses (PR) and 9 achieved stable disease (SD) in Best of Response.1 subject who had received 2-line treatment with multiple metastases (including lung, bones, liver and adrenal gland) had achieved PR since the first tumor assessment, target lesion decreased by up to 52.1% from baseline. 1 subject who had received 2-line treatment with lung and lymph node metastasis had achieved PR since the first tumor assessment, target lesion decreased by up to 40.3% from baseline. Both two patients, duration of treatment was over 6 months and still in PR status when discontinued treatment. The ORR was 13.3% (95%CI: 1.7-40.5) and DCR was 73.3% (95%CI: 44.9-92.2). Median PFS was not reached. For all enrolled pts, 17 pts (100%) experienced a treatment related adverse events (TRAE). The most common TRAEs were proteinuria (58.8%, 10/17), hypoalbuminemia 6/9 (35.3%, 6/17), hypercholesterolemia (35.3%, 6/17), hyperuricemia (29.4%, 5/17). TRAEs ≥ grade 3 occurred in 6 (35.5%) patients and no death occurred. TRAE leading to discontinuation occurred in 3 (17.7%) pts. Conclusions: HB0025 10mg/kg monotherapy showed an acceptable safety profile and promising anti-tumor activity in prior multiple treated RCC, which supports further studies to explore the safety and efficacy of HB0025 as a monotherapy or in combination with other anti-tumor agents. HB0025 20mg/kg monotherapy study are currently ongoing. Clinical trial information: NCT06222125 .