Hanmi Pharmaceutical and Beijing Hanmi Pharmaceutical are advancing clinical trials for BH3120, a novel immunotherapy, as presented at the Society for Immunotherapy of Cancer (SITC) conference. The Phase 1 trials are evaluating BH3120, both as a monotherapy and in combination with Merck's pembrolizumab (KEYTRUDA), in patients with advanced or metastatic solid tumors.
BH3120 leverages Hanmi's Pentambody platform, a dual-antibody technology that allows a single antibody to bind two distinct targets simultaneously. This approach aims to enhance anti-cancer activity by directly targeting cancer cells while activating immune cells.
Novel Mechanism of Action
BH3120 is designed to target PD-L1, a protein expressed on cancer cells that suppresses immune responses, and 4-1BB, an immune cell receptor that stimulates immune cell activation. By binding to both targets, BH3120 acts as a bridge, facilitating the recognition and killing of tumor cells by immune cells.
Preclinical Efficacy and Safety
Preclinical studies have demonstrated that BH3120 exhibits robust anti-cancer efficacy with a unique decoupling of immune activity between the tumor microenvironment (TME) and normal tissues. This is particularly notable as other 4-1BB-targeting antibody candidates have encountered challenges related to either anti-cancer efficacy or safety. The distinct mechanism of BH3120 suggests it may offer a more effective and safer approach to cancer immunotherapy.
Phase 1 Clinical Trial Progress
The ongoing global Phase 1 clinical trial is assessing the safety and tolerability of BH3120 as a monotherapy in patients with advanced or metastatic solid tumors. The trial has progressed through cohort 3 (1 mg/kg) of the dose escalation phase without observing any dose-limiting toxicities (DLT) or grade 3 or higher adverse drug reactions to date.
Dr. Dong-wan Kim, lead investigator for the Phase 1 clinical trial of BH3120 at Seoul National University Hospital Clinical Trials Center, stated, "The phase 1 clinical trial of BH3120 is a critical step in verifying the potential of this next-generation immunotherapy. We are optimistic about achieving positive outcomes." He further added, "We hope further research will establish BH3120 as an effective and safe treatment option for various cancer types, reducing the side effects often associated with current immunotherapies."
Combination Trial with Pembrolizumab
In addition to the monotherapy trial, Hanmi is also conducting a Phase 1 trial to evaluate the safety and efficacy of BH3120 in combination with pembrolizumab in patients with advanced or metastatic solid tumors. Regulatory approvals to modify the Phase 1 trial plan to include the combination therapy were obtained from both the Korean Ministry of Food and Drug Safety and the U.S. Food and Drug Administration (FDA) in September. Full-scale clinical development is expected to commence early next year, with Hanmi as the lead sponsor and Merck supplying pembrolizumab.
Young Su Noh, Director of Hanmi’s ONCO Clinical Team, emphasized, “The BH3120 trial represents a milestone as Hanmi’s first global clinical research project utilizing our proprietary Pentambody dual antibody platform in immuno-oncology, a field at the forefront of cancer treatment innovation.” He continued, “We are committed to advancing a next-generation immunotherapy that overcomes the limitations of existing treatments and enhances therapeutic efficacy.”
