The second DMC review recommends the continuation of dose escalation in the clinical trial as per protocol. The interim safety assessment was based on the review of safety data from 18 metastatic gastrointestinal cancer patients, including patients that have tolerated multiple doses of cabotamig. The DMC review confirms the safety risk profile of cabotamig being consistent with published T-cell engagers.
SEATTLE, April 26, 2024 /PRNewswire/ — Arbele, a clinical-stage biotechnology company focused on the development of novel immunotherapies targeted for advanced gastrointestinal cancers, today announced the positive recommendation from the second meeting of the Data Monitoring Committee (DMC) to continue the A001 Phase I clinical trial evaluating cabotamig (ARB202) in patients with advanced gastrointestinal (GI) cancers without modification to the trial protocol. The DMC, composed of a group of independent experts, arrived at this recommendation after review of the interim safety data of patients enrolled in the A001 trial.
This safety assessment was based on the review of safety data from 18 patients, including patients that have been treated with multiple doses of cabotamig. This positive recommendation confirms tolerability profile of cabotamig is consistent with published safety data of T-cells engagers in other indications.
"We are greatly indebted to the courageous subjects who have participated in this early study of cabotamig that have allowed us better understand the safety profile while optimizing the dosing of this promising therapy" said Dr Dennis Wong, Chief Medical Officer at Arbele.
About A001 Trial
The A001 trial is a multi-center, open label, FIH continuous study designed to evaluate the safety, tolerability, PK, PD, and anti-tumor activity of cabotamig administered intravenously in patients with unresponsive advanced GI malignancies expressing CDH17. The first part of the study consists of a dose-escalation stage (single ascending doses (SAD) Phase Ia) enrolling approximately 28 patients, and then a multiple dose ascending/ranging study (MAD).
Except for colorectal cancer patients, all other patients are screened for tumors expressing CDH17 using TibTech™ proprietary automated tissue diagnostic platform. If CDH17 is expressed, patients will be eligible to enter screening to be dosed. Colorectal cancer patients may be eligible without CDH17 marker testing.
For more information about A001, visit https://clinicaltrials.gov/study/NCT05411133.
About Cabotamig
ARB202 is a first-in-class bispecific antibody based on Arbele’s patented CDH17 biomarker. It targets both CDH17 on GI cancer as well as CD3 on T cells. The unique differential binding affinities of ARB202 toward CDH17 and CD3 allows it to have high specificity and cytotoxicity, while avoiding the "on-target" normal CDH17 expressing cells. Preclinical data showed that ARB202 can facilitate T-cell attachment to cancer cells, activation and release of IL-2, thereby demonstrating target engagement activation and cytotoxicity.
About CDH17
Cadherin-17 (CDH17) is an adhesion molecule that binds to self and integrin α2β1. Its expression in humans is limited to gastrointestinal tissue, most studied in the adherens junctions along with E-cadherin on the basal lateral surface of colon epithelial cells. Its expression is tightly regulated and believed to be involved in the tight control of solutes between epithelial cells in the gut which prevents the movement of water and proteins into the lumen. Its aberrant expression at the cell surface in GI neoplastic cells has been well documented. CDH17 has been shown to be involved in cancer progression and is associated with poor prognosis. The soluble form, sCDH17 was previously found to increase with tumor staging and decrease with tumor debulking. Given CDH17 is expressed de novo or overexpressed at abnormally levels in GI cancers including CRC, GEJ, CCA, and PDAC, it provides a way to target T-cells to GI malignant cells within a suppressive tumor micro-environment.
About Arbele
Arbele is founded in 2016 by former senior executives from multinational pharmaceutical companies, with R&D presence in Seattle, Sydney, Singapore and Hong Kong. It focuses on the development of breakthrough diagnostic platforms and innovative immunotherapy; to provide early intervention and treatment for people with gastrointestinal cancers including but not limited to colorectal cancer, pancreatic cancer, gastric cancer, gastroesophageal junction cancer, liver cancer and cholangiocarcinoma, for which effective treatment options are scanty with high mortality rates. For more information on ARBELE, please visit http://www.arbelebio.com/
Media and Investor Contact:Dr Diana Hay, PhDExecutive Director, Business Development & IPdiana.hay@arbelebio.com
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