Harbour BioMed Publishes Phase I Study Results for Porustobart and Toripalimab in Advanced Melanoma and Solid Tumors

Harbour BioMed, a global biopharmaceutical company focused on oncology and immunology, has announced the publication of results from its phase I clinical trial of porustobart (HBM4003), a novel fully human heavy chain antibody targeting CTLA-4. The study evaluated the efficacy and safety of porustobart in combination with the anti-PD-1 antibody toripalimab for treating advanced solid tumors, with a significant emphasis on melanoma. The findings were published in the Journal for ImmunoTherapy of Cancer.

The multicenter, open-label phase I trial was spearheaded by Dr. Jun Guo from Beijing Cancer Hospital. The study revealed that the combination of porustobart and toripalimab exhibited a manageable safety profile without any new safety concerns. Initial results suggested significant antitumor activity, especially in PD-1 treatment-naïve mucosal melanoma patients.

Dual immunotherapy using anti-CTLA-4 and anti-PD-1 antibodies is an approved frontline treatment for multiple solid tumors, such as melanoma, renal cell carcinoma, and non-small cell lung cancer. However, the high toxicity associated with anti-CTLA-4 antibodies has hindered their extensive use. Porustobart, a next-generation fully human anti-CTLA-4 antibody developed using the HCAb Harbour Mice® platform, is the first such antibody to undergo clinical trials globally. Its distinctive attributes offer the potential to address the efficacy and toxicity issues linked with conventional anti-CTLA-4 therapies, positioning it as a promising candidate in cancer immunotherapy.

The phase I trial was divided into two stages: a dose-escalation phase (Part 1) and a dose-expansion phase (Part 2). A total of 40 patients participated, with the treatment aimed at assessing the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of the combination therapy for solid tumors, particularly melanoma.

In terms of safety, 10 out of 40 patients (25.0%) reported grade 3 or higher treatment-related adverse events (TRAEs). Commonly reported adverse events included rash (30.0%), abnormal liver function (30.0%), leukopenia (25.0%), and fever (20.0%). Additionally, 5 patients (12.5%) experienced immune-related adverse events (irAEs) with a maximum severity of Grade 3. No Grade 4 or 5 irAEs were reported.

Efficacy was evaluated 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), each having post-baseline imaging data available. The objective response rate (ORR) was 33.3% in the anti-PD-1/PD-L1 treatment-naïve subgroup. For patients with mucosal melanoma in the anti-PD-1/PD-L1 treatment-naïve subgroup, the ORR was 40.0%. A high baseline Treg/CD4+ ratio in the tumor was identified as an independent predictive factor for immunotherapy efficacy.

In conclusion, the combination of porustobart 0.3 mg/kg with toripalimab 240 mg Q3W showed promising antitumor activity and manageable safety in patients with advanced melanoma, including mucosal subtypes. Further studies are necessary to confirm these findings, particularly in patients with mucosal melanoma.

Dr. Jingsong Wang, Founder, Chairman, and CEO of Harbour BioMed, expressed optimism about the positive results from the phase I study, noting the favorable safety profile and early signs of clinical activity. He highlighted that porustobart is the first internally developed molecule from the HCAb Harbour Mice® platform and expressed eagerness to advance further studies to explore the full potential of this combination in addressing unmet medical needs and improving patient outcomes.

Porustobart (HBM4003) is a fully human anti-CTLA-4 monoclonal heavy chain only antibody generated from Harbour Mice®. It is the first fully human heavy-chain-only monoclonal antibody to enter the clinical stage globally. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, porustobart has shown significant improvement in depleting high CTLA-4 expressing Treg cells in tumor tissues. This has resulted in potent antitumor efficacy and differentiated pharmacokinetics with a durable pharmacodynamic effect, presenting a favorable product profile. This novel mechanism has the potential to improve efficacy while significantly reducing drug toxicity in both monotherapy and combination therapy.

Harbour BioMed is dedicated to discovering, developing, and commercializing novel antibody therapeutics with a focus on immunology and oncology. The company leverages its proprietary antibody technology platforms, Harbour Mice® and HBICE®, to generate fully human monoclonal antibodies and bispecific antibodies for next-generation therapeutic applications.