Harbour BioMed announced the results of phase Ib clinical trial of porustobart (HBM4003), in combination of toripalimab in patients with hepatocellular carcinoma (HCC) (trial code: NCT05149027) were released at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023. This is an open-label Phase Ib dose expansion study to evaluate the safety, tolerability, PK/PD and preliminary efficacy of HBM4003 in combination with toripalimab in patients With advanced HCC and other solid tumors. Patients with advanced HCC (n=28) received porustobart 0.45 mg/kg plus toripalimab 240 mg every three weeks (Q3W) in both Cohort 1 and Cohort 2. Cohort 1 recruited patients who failed previous anti-VEGFR multikinase inhitor(s) treatment while have not received anti-PD-(L)1 treatment (n=16); Cohort 2 recruited patients who failed previous anti thePD-(L)1 and anti-VEGF(R) treatments (n=12).

The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: As of 9 December 2022, 28 patients had been dosed. The median follow-up time was 3.6 months; Porustobart in combination of toripalimibitor(s) were 46.7% and 73.3%, respectively in 15 patients with post-treatment tumor assessments; In Cohort 2, the ORR and DCR were 9.1% (18.2% per mRECIST) and 54.5%, respectively in 11 patients with post-treatment tumor assessment; Porustobart in collaboration of toripalimab showed acceptable safety profile in HCC; Treatment-related adverse events (TRAEs) were reported in 89.3% (25/28) patients, and Grade 3 TRAEs were reported in 39.3% (11/28) patients. No Grade 4 or Grade 5 TRAE was reported.

Porustobart in combinationof toripalimab showed favorable PK/PD signature. Porustobart promoted the clearance of Treg cells and the proliferation CD4+ and CD8+ T cell in periphery assessed to its mechanism of action. Greater effects were observed in Cohort 1, suggested a larger available pool of effectors to induce anti-tumor activity in the presence of effective Treg depletion.

No noticeable differences in PK between Cohort 1 and Cohort 2 were observed. Porustobart 0.45 mg/kg plus toripalimab 240 mg Q3W showed promising anti-tumor activity and an acceptable safety profile in patients with advanced HCC. Porustobart is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice®.

By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, porustobart has demonstrated significantly improved depletion specific to high CTLA-4 Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect presents a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug in monotherapy and combo-therapy.