The U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for ADCE-T02, a novel antibody-drug conjugate (ADC) developed by Copenhagen-based Adcendo ApS. This milestone enables the initiation of Phase I clinical trials in the United States for patients with advanced solid tumors.
ADCE-T02 represents a potential breakthrough as the first Topoisomerase I inhibitor-based ADC targeting tissue factor (TF), a protein notably overexpressed in multiple solid tumors. The drug's development addresses significant unmet needs in several cancer types, including cervical, head and neck, colorectal, non-small cell lung cancer, and pancreatic ductal adenocarcinoma.
Trial Design and Objectives
The Tiffany-01 trial, a first-in-human Phase I study, is designed as a multicenter, open-label, dose escalation study evaluating ADCE-T02 as monotherapy. Currently active in Australia, the trial will expand to U.S. sites in the coming months. The study's primary objectives include:
- Determining the maximum tolerated dose
- Establishing the recommended Phase II dose and schedule
- Assessing safety and tolerability
Secondary objectives focus on characterizing pharmacokinetics and evaluating preliminary efficacy in the target patient population.
Innovative Drug Design
ADCE-T02's development addresses key limitations of existing TF-targeting ADCs. Dr. Lone Ottesen, Chief Medical Officer of Adcendo, explains: "The currently approved TF targeting ADC has severe limitations due to a suboptimal side effect profile and a limited therapeutic window. The highly differentiated profile of ADCE-T02, based on the use of an improved monoclonal antibody and a next generation Topoisomerase I inhibitor linker/payload technology, could overcome those limitations."
Key technological advantages of ADCE-T02 include:
- Minimized impact on the coagulation pathway through unique antibody design
- Enhanced bystander effect via T1000-exatecan linker-payload technology
- Improved linker stability
- Potential to overcome emerging resistance mechanisms
Clinical Perspective
Professor Vinod Ganju, Managing Director of Peninsula and Southeast Oncology in Melbourne and Principal Investigator of Tiffany-01, highlighted the growing importance of ADCs in cancer treatment: "ADCs have in the past years shown highly encouraging results and have already become Standard of Care in quite a number of solid tumor indications. ADCE-T02 represents an attractive new option to explore in advanced solid tumors with high unmet need."
The drug's development strategy focuses on achieving a broader therapeutic window and enhanced safety profile compared to existing treatments. This approach could potentially lead to improved clinical outcomes across multiple solid tumor indications where current treatment options remain limited.
