Depatuxizumab

Enrollment has opened in a first-in-human Phase I trial of APTN-101, an EGFRvIII-targeted bispecific T cell engager developed by Charlotte, North Carolina-based Adaptin Bio, Inc. (OTCQB: APTN) for patients with World Health Organization Grade IV malignant glioma. The trial is being conducted at Duke University's Preston Robert Tisch Brain Tumor Center, where the underlying BRiTE (Brain Bispecific T cell Engager) technology was developed. APTN-101 is designed to address two major barriers to immunotherapy in glioblastoma (GBM): drug penetration across the blood-brain barrier (BBB) and selective targeting of tumor cells. The BRiTE approach targets EGFRvIII, a tumor-specific EGFR variant found in a subset of GBMs, while using what Adaptin describes as an immune-cell "hitchhiking" mechanism to improve delivery of the T cell engager into the brain. In preclinical models, Adaptin reported that the approach increased brain distribution of the EGFRvIII T cell engager by more than seven-fold compared with administration of the engager alone and produced complete tumor eradication in 70%–80% of EGFRvIII-positive GBM mouse models. The findings have not yet been validated clinically, and the company has not published the preclinical dataset in a peer-reviewed journal. EGFRvIII has previously proved difficult to translate into an effective therapeutic target. Celldex Therapeutics' EGFRvIII vaccine rindopepimut failed to improve overall survival in the Phase III ACT IV trial, while AbbVie's EGFR-directed antibody-drug conjugate depatuxizumab mafodotin was discontinued after the Phase III INTELLANCE-1 study also failed to demonstrate an overall survival benefit. The open-label, dose-escalation Phase I study will enroll up to 15 adults with EGFRvIII-positive Grade IV malignant glioma. Its primary objectives are to assess dose-limiting toxicities and establish the maximum tolerated dose. Secondary endpoints include pharmacokinetics and objective response rate using modified Response Assessment in Neuro-Oncology (RANO) criteria, while exploratory measures include cytokine changes, anti-BRiTE antibodies, progression-free survival, and overall survival. Mustafa Khasraw, professor at Duke University School of Medicine, is the principal investigator. The US FDA cleared APTN-101's investigational new drug (IND) application in September 2024, with Duke granting institutional review board approval in January 2026. The opening of enrollment therefore marks the program's transition into human testing nearly two years after the IND clearance. No EGFRvIII-targeted therapy has received regulatory approval. With only 15 patients planned and no clinical data yet available, the study is primarily an initial test of whether the BBB-delivery and tumor-targeting properties reported in preclinical models can be reproduced safely in humans. Access the AllSci platform to explore the science behind the news. Spot something wrong? Report an issue with this article