A phase 1/2 study to evaluate the efficacy and safety of HB0025 monotherapy for patients (pts) with advanced renal cell carcinoma (RCC).

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 .