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Harbour BioMed Reports the Latest Progress from Phase I Clinical Trial of Porustobart in Combination with Toripalimab in Advanced Melanoma

December 08, 2022

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Harbour BioMed Reports the Latest Progress from Phase I Clinical Trial of Porustobart in Combination with Toripalimab in Advanced Melanoma

December 08, 2022

Cambridge, MA, Rotterdam, NL, Suzhou, CN— December 8, 2022


Harbour BioMed (the “Company”, HKEX: 02142), today announced the progress of its dual MOA of CTLA-4 inhibition and Treg depletion, next-generation fully human heavy-chain antibody porustobart (HBM4003) in phase I clinical trial of combination therapy with toripalimab in advanced melanoma and other solid tumors. The clinical data abstract (#152P) has been published at the European Society for Medical Immuno-Oncology (ESMO I-O) 2022 Annual Congress.



Study Design and Highlights


This is an open-label study to evaluate the safety, tolerability, pharmacokinetics (PK)/ pharmacodynamic (PD) and preliminary efficacy of HBM4003 in combination with toripalimab in patients with advanced melanoma and other solid tumors.


It includes two parts: (i) in the dose-escalation part, patients with solid tumors received HBM4003 at 3 dose levels (1 patient received 0.03 mg/kg, 3 patients received 0.1 mg/kg, and 10 patients received 0.3 mg/kg) plus toripalimab 240 mg every three weeks (Q3W); (ii) in the dose-expansion part, 26 patients with advanced melanoma received the recommended phase 2 dose (RP2D) of HBM4003 0.3 mg/kg plus toripalimab 240 mg Q3W.


  1. As of 31 August 2022, a total of 40 patients had been dosed and the median follow-up time was 106.5 days


  1. HBM4003 in combination of toripalimab in advanced melanoma showed a favourable safety profile. Treatment-related adverse events (TRAEs) were reported in 87.5% (35/40) patients, and ≥Grade 3 TRAEs were reported in 20.0% (8/40) patients. The most commonly reported TRAE was rash (30.0%)


  1. HBM4003 in combination of toripalimab showed great anti-tumor activity regardless of prior-line treatment


34 patients with advanced melanoma treated with RP2D (including 8 patients in dose-escalation part and 26 patients in dose-expansion part) were categorized as anti-PD-(L)1 naïve group (17 patients) and anti-PD-(L)1 pretreated group (17 patients).


  • In anti-PD-(L)1 naïve group, the overall response rate (ORR) and disease control rate (DCR) were 53.3% (95%CI: 26.6-78.7) and 73.3% (95%CI: 44.9-92.2) respectively in the 15 patients with post-treatment tumor assessment. The ORR of cutaneous, acral, mucosal and unknown subtype were 66.7% (2/3), 50% (2/4), 60.0% (3/5) and 33.3% (1/3), respectively.
  • In anti-PD-(L)1 pretreated group, the ORR and DCR were 11.8% (95%CI: 1.5-36.4) and 35.3% (95%CI: 14.2-61.7) respectively. Both of the partial response (PR) cases were mucosal subtype, including one patient achieving PR after pseudo-progression.




HBM4003 demonstrated robust clinical response rate in difficult-to-treat melanoma subtypes in Asians, such as mucosal and acral melanoma that were generally not sensitive to immunotherapy including PD-(L)1. HBM4003 0.3 mg/kg plus toripalimab 240mg Q3W showed promising anti-tumor activity in patients with advanced melanoma including acral and mucosal subtypes, as well as an acceptable safety profile. The results showed great potential to develop HBM4003 as a cornerstone therapy in immuno-oncology. The Company is also conducting other clinical studies of combination therapy for other advanced solid tumors, such as hepatocellular carcinoma and neuroendocrine tumors/neuroendocrine carcinoma.


Dr. Humphrey Gardner, CMO of Harbour BioMed, commented on the study’s results, “we are excited to observe the promising efficacy of porustobart and its potential to lead the development of next-generation therapy of immuno-oncology for multiple solid tumors. The Treg depleting activity of HBM4003 offers a potential for clinical efficacy in indications hitherto unaddressed by first generation CTLA4 inhibitors. We will continue to fully commit to advancing the global clinical development of porustobart to address the significant unmet medical needs in multiple solid tumor indications.”



About Porustobart (HBM4003)


Porustobart is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice®. It is the first fully human heavy-chain-only monoclonal antibody entered into clinical stage globally. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, porustobart has demonstrated significantly improved depletion specific to high CTLA-4 expressing 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 combination therapy.


About Harbour BioMed


Harbour BioMed (HKEX: 02142) is a global biopharmaceutical company committed to the discovery, development and commercialization of novel antibody therapeutics focusing on immunology and oncology. The Company is building its robust portfolio and differentiated pipeline through internal R&D capability, collaborations with co-discovery and co-development partners and select acquisitions.
The Company’s proprietary antibody technology platforms Harbour Mice® generate fully human monoclonal antibodies in two heavy and two light chain (H2L2) format, as well as heavy chain only (HCAb) format. Building upon the HCAb antibodies, the HCAb-based immune cell engagers (HBICE®) are capable of delivering tumor killing effects unachievable by traditional combination therapies. Integrating Harbour Mice®, HBICE® with single B cell cloning platform, our antibody discovery engine is highly unique and efficient for development of next generation therapeutic antibodies.  

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