ABL Bio has secured regulatory approval from South Korea's Ministry of Food and Drug Safety (MFDS) for a phase 1b/2 clinical trial evaluating a triple combination therapy featuring its bispecific antibody ABL103 alongside pembrolizumab (Keytruda) and taxane chemotherapy for patients with solid tumors.
The approval represents a significant milestone for ABL Bio's immunotherapy development program, building on ongoing phase 1 monotherapy trials of ABL103 currently underway in the United States and South Korea. The company has entered into a clinical trial collaboration and supply agreement with MSD, a subsidiary of Merck & Co., which will provide pembrolizumab for the combination study.
Novel Bispecific Antibody Mechanism
ABL103 is engineered as a bispecific antibody that simultaneously targets B7-H4 antigens present on tumors and 4-1BB antigens that activate immune cells. The drug utilizes ABL Bio's proprietary Grabbody-T platform, which is designed to activate T cells specifically within the tumor microenvironment while reducing the burden of liver toxicity associated with systemic 4-1BB activation.
Preclinical data presented at AACR 2025 demonstrated that ABL103 shows synergistic immune responses when combined with pembrolizumab in immunosuppressive tumor microenvironments. According to the research findings, the combination leads to synergistic activation of T cells and facilitates the transition of "cold" tumor microenvironments to inflammatory states, suggesting enhanced therapeutic potential compared to monotherapy approaches.
Comprehensive Trial Design
The phase 1b/2 clinical trial will consist of two safety lead-in parts designed to determine the appropriate dosage for the triple combination therapy, followed by one dose expansion part. The study will be conducted across multiple countries including South Korea, the United States, and Australia, with plans to evaluate both safety and efficacy of the ABL103 triple combination therapy.
ABL Bio plans to amend its existing investigational new drug (IND) application for the ongoing phase 1 monotherapy trial to include this phase 1b/2 combination study. The dose escalation portion will monitor adverse reactions while increasing dosage levels, with the subsequent tumor expansion part planned for approximately 60 patients, though the final patient number will be determined based on dose escalation data.
Broader Pipeline Development
The regulatory approval comes as part of ABL Bio's broader 4-1BB-based bispecific antibody development program. The company recently completed a third-party allocation paid-in capital increase worth 140 billion won to support development of its next-generation dual antibody ADC platform and existing immunotherapy programs.
Other compounds in ABL Bio's pipeline include ABL503 and ABL111, which are currently undergoing phase 1 tumor expansion and triple combination therapy evaluation trials respectively. ABL105, targeting breast and gastric cancers, is progressing through phase 1 clinical trials in Korea and Australia, with phase 1 clinical data for both ABL105 and ABL103 expected to be announced in 2025.
"We look forward to the combination of ABL103, Keytruda, and taxane opening up new treatments for intractable solid cancer patients," said Sanghoon Lee, CEO of ABL Bio. "As the clinical trial of 4-1BB-based double antibodies, including ABL103, is progressing smoothly, we will do our best to research and develop it so that we can deliver good news."
The approval process, which typically takes up to three months, was completed in approximately one month, indicating regulatory support for the innovative therapeutic approach. ABL Bio has also disclosed preclinical data showing ABL103's anticancer effects correlate with B7-H4 expression levels, with particular efficacy demonstrated in breast and ovarian cancers, including triple-negative breast cancer.
