ABL111 (TJ033721, Givastomig), a bispecific antibody drug candidate developed by ABL Bio, has been selected as a key pipeline program by its global partner, I-Mab. This decision underscores the potential of ABL111 in the treatment of gastric and esophageal cancers.
Development and Mechanism
ABL111 targets Claudin18.2 and 4-1BB, utilizing ABL Bio's 4-1BB-based bispecific antibody platform, Grabody-T. It activates T-cells via 4-1BB in the tumor microenvironment where Claudin18.2 is expressed, thereby targeting Claudin18.2-positive tumors. This mechanism aims to attack tumor cells while sparing normal cells, minimizing hepatotoxicity and systemic immunotoxicity.
Clinical Trials
ABL Bio and I-Mab are co-developing ABL111 as a first-line treatment for gastric and esophageal cancer. They are conducting a phase 1b clinical trial of ABL111 in combination with the anti-PD-1 immuno-oncology drug Opdivo (nivolumab) and chemotherapy (FOLFOX) in the U.S. and China. The trial focuses on treatment-naïve patients with Claudin 18.2-positive metastatic gastric cancer.
Interim Results
Interim phase 1 results of ABL111 monotherapy, presented at ESMO 2024, showed that seven of 43 patients with gastric and esophageal cancer achieved a partial response (PR), resulting in an overall response rate (ORR) of 16.3 percent. Major adverse events were mostly grade 1-2, with no dose-limiting toxicities (DLTs) or maximum tolerated doses (MTDs) identified.
Future Plans
I-Mab has completed patient recruitment in the 17-patient Dose Escalation study and is conducting a Dose Expansion study in 40 patients. Data from the Dose Escalation study are expected later this year, with results from the Dose Expansion study anticipated in early 2026.
Strategic Focus
In a strategic shift, I-Mab has decided to suspend the development of uliledlimab to focus on ABL111, highlighting the drug's potential in treating a low-expressing patient population ineligible for approved Claudin 18.2 therapies. I-Mab's Chief Medical Officer, Phillip Dennis, emphasized the study's confirmation of Givastomig's potential and the establishment of a recommended dose for follow-up studies.
