The U.S. Food and Drug Administration has granted Fast Track designation to ADCE-D01, a first-in-class antibody-drug conjugate developed by Copenhagen-based Adcendo ApS for the treatment of soft tissue sarcoma. The designation recognizes the potential of this novel therapeutic approach to address significant unmet clinical needs in sarcoma treatment.
Novel Target and Mechanism of Action
ADCE-D01 represents a breakthrough in sarcoma therapeutics by targeting urokinase plasminogen activator receptor-associated protein (uPARAP), a novel endocytic ADC target that is overexpressed in tumors of mesenchymal origin, including sarcomas. The drug conjugates this targeting mechanism with P1021, a Topoisomerase I inhibitor payload, creating a precision therapy designed specifically for mesenchymal cancers.
Preclinical studies demonstrate that ADCE-D01 exhibits strong anti-tumor activity across a range of mesenchymal tumor models, including soft tissue sarcoma. The drug candidate has shown a favorable safety profile in non-human primate toxicology studies, with no evidence of target-specific toxicity, supporting its advancement into human clinical trials.
Current Clinical Development
ADCE-D01 is currently under evaluation in the ADCElerate1 clinical trial, a first-in-human Phase I/II multicenter, open-label, dose escalation and expansion study. The trial is assessing ADCE-D01 as a monotherapy in patients with metastatic and/or unresectable soft tissue sarcoma, with recruitment ongoing in both the United States and Europe.
The study's primary objective focuses on evaluating the safety and tolerability of ADCE-D01, while secondary objectives include characterizing the drug's pharmacokinetics and assessing preliminary efficacy. The trial is registered under NCT06797999 in the US and EUCT number 2024-516900-41-00 in Europe.
Regulatory Advantages and Future Outlook
The Fast Track designation provides Adcendo with enhanced access to FDA guidance and more frequent regulatory interactions, potentially accelerating the development timeline for ADCE-D01. This designation also makes the drug candidate eligible for additional expedited pathways, including Accelerated Approval and Priority Review if relevant criteria are met, as well as Rolling Review procedures.
Dr. Lone Ottesen, Chief Medical Officer of Adcendo, emphasized the significance of this milestone: "This Fast Track designation is an important recognition of the potential of our uPARAP-targeting drug candidate and marks another meaningful milestone for Adcendo. We are committed to further advancing ADCE-D01 and believe that our uPARAP-targeting approach has the potential to transform the sarcoma treatment landscape and overcome the limitations experienced with existing therapies."
Dr. Victoria Marsh, Global Head of Regulatory at Adcendo, highlighted the practical benefits of the designation: "With this Fast Track designation the development of ADCE-D01 will now benefit from more frequent interactions with the FDA. Increased FDA engagement will support and expedite the future regulatory review of ADCE-D01 with the aim of making ADCE-D01 available to patients sooner."
