Harbour BioMed announced the publication of Phase I clinical trial results for porustobart (HBM4003) in combination with toripalimab for treating advanced solid tumors, with a focus on melanoma. Published in the Journal for ImmunoTherapy of Cancer, the study (IF=10.3, 2023) revealed a manageable safety profile and promising antitumor activity, especially in PD-1 treatment-naïve mucosal melanoma.
The multicenter, open-label Phase I trial, led by Dr. Jun Guo at Beijing Cancer Hospital, evaluated the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of the combination therapy in 40 patients with advanced solid tumors. The study included a dose-escalation phase and a dose-expansion phase.
Safety and Efficacy
The combination of porustobart and toripalimab showed a manageable safety profile, with 25.0% of patients reporting grade ≥3 treatment-related adverse events (TRAEs). Common TRAEs included rash (30.0%), abnormal liver function (30.0%), leukopenia (25.0%), and fever (20.0%). Immune-related adverse events (irAEs) of Grade 3 or lower were observed in 12.5% of patients, with no Grade 4 or 5 irAEs reported.
Efficacy was assessed in 32 melanoma patients treated with the recommended Phase II dose (RP2D) of porustobart 0.3 mg/kg combined with toripalimab 240 mg every three weeks (Q3W). These patients had available post-baseline imaging data. The objective response rate (ORR) was 33.3% in the anti-PD-1/PD-L1 treatment-naïve subgroup. Notably, for patients with mucosal melanoma, the ORR in this anti-PD-1/PD-L1 treatment-naïve subgroup was 40.0%. Researchers identified a high baseline Treg/CD4+ ratio in the tumor as an independent predictive factor for immunotherapy efficacy.
Addressing Unmet Needs in Melanoma Treatment
Dual immunotherapy combining anti-CTLA-4 and anti-PD-1 antibodies is a frontline treatment for several solid tumors. However, the high toxicity associated with anti-CTLA-4 antibodies has limited their broader use. Porustobart, a next-generation fully human anti-CTLA-4 antibody, aims to overcome these challenges. Developed using the HCAb Harbour Mice® platform, porustobart is designed to improve efficacy while reducing toxicity.
Porustobart's Novel Mechanism
Porustobart (HBM4003) is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb). It enhances antibody-dependent cell cytotoxicity (ADCC) killing activity, leading to improved depletion specific to high CTLA-4 expressing Treg cells in tumor tissues. This mechanism offers a differentiated approach with the potential to improve efficacy and reduce toxicity in both monotherapy and combination therapy.
"We are encouraged by the positive results from our phase I study of porustobart in combination with an anti-PD-1 antibody, which has shown a favorable safety profile and early signs of clinical activity," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed. "We look forward to moving forward with further studies to fully explore the potential of this combination in addressing unmet medical needs and ultimately making a meaningful difference in patients' lives."
