Ratio Therapeutics Doses First Patients in Phase 1/2 Trial of FAP-Targeted Radiopharmaceutical for Aggressive Sarcomas
核心洞察
Ratio Therapeutics (搜索) has successfully completed dosing of the first cohort in the ATLAS Phase 1/2 trial evaluating [Ac-225]-RTX-2358 (搜索), a novel FAP (搜索)-targeted radiopharmaceutical for relapsed or refractory soft tissue sarcomas.
The investigational therapy uses Actinium-225 to deliver targeted radiation directly to tumors expressing fibroblast activation protein-α (搜索) (FAP (搜索)), potentially offering a new treatment approach for patients with limited options.
The study employs a 3+3 dose escalation design in Phase 1 to determine maximum tolerated dose, with plans to evaluate up to 26 patients before expanding to 50 patients in Phase 2.
Ratio Therapeutics (搜索) has achieved a significant milestone by successfully dosing the first cohort of patients in its ATLAS Phase 1/2 clinical trial evaluating [Ac-225]-RTX-2358 (搜索), a novel fibroblast activation protein-α (搜索) (FAP (搜索))-targeted radiopharmaceutical for patients with relapsed or refractory soft tissue sarcomas. The investigational therapy was manufactured and supplied by PharmaLogic Holdings Corp (搜索). from its radiopharmaceutical facility in the Bronx, New York.
Novel Radiopharmaceutical Approach
[Ac-225]-RTX-2358 (搜索) represents a highly selective FAP (搜索)-targeted radiotherapeutic labeled with Actinium-225, designed to deliver radiation directly to tumors with enhanced precision. The therapy addresses a critical unmet need for patients with relapsed or refractory soft tissue sarcomas, a population with limited treatment options.
"Advancing [Ac-225]-RTX-2358 (搜索) into the clinic represents a major milestone for our company and reflects years of dedicated and innovative work by our team," said John Babich, Ph.D., President and Chief Scientific Officer of Ratio Therapeutics (搜索). "The preclinical and early human experience point to a strong therapeutic profile for our drug in sarcoma, with encouraging signs of activity in additional FAP (搜索)-expressing cancers."
ATLAS Trial Design and Patient Selection
The ATLAS trial (NCT07156565) is structured as a Phase 1/2 open-label study designed to assess safety, tolerability, dosimetry, biodistribution, pharmacokinetics, and preliminary anti-tumor activity of [Ac-225]-RTX-2358 (搜索). Patient eligibility requires FAP (搜索) expression assessment using a [Cu-64]-LNTH-1363S (搜索) PET scan provided by Lantheus (搜索) and manufactured by PharmaLogic.
The Phase 1 portion employs a standard 3+3 dose escalation design with participants assigned to three groups receiving increasing dose levels to determine the maximum tolerated dose. Patients with FAP (搜索)-positive sarcomas receive intravenous injections once every eight weeks for up to six treatment cycles over a 12-month period. Cohort expansion allows up to 10 patients per cohort, enabling evaluation of up to 26 patients during Phase 1 for better characterization of safety, tolerability, and preliminary efficacy assessment.
An independent Safety Review Committee reviews safety data from each group before dose escalation proceeds. The Phase 2 portion will evaluate efficacy and safety in up to 50 patients.
Clinical Significance and Manufacturing Partnership
Dr. Sandra D'Angelo, a Medical Oncologist specializing in sarcoma care at Memorial Sloan Kettering Cancer Center, emphasized the study's importance: "This study represents an important step in exploring a novel therapeutic approach for patients with relapsed or refractory sarcoma, a population with limited treatment options. Radiopharmaceuticals are transforming cancer treatment by delivering radiation directly to tumors with far greater precision and decreased side effects."
The successful supply of first cohort dosing demonstrates the strength of the manufacturing partnership between Ratio Therapeutics (搜索) and PharmaLogic. "PharmaLogic is proud of this collaboration with Ratio Therapeutics and the advancement of [Ac-225]-RTX-2358 (搜索) into the clinic," said Etienne Montagut, President and CEO of PharmaLogic. "The supply of the first cohort doses from our Bronx facility underscores our commitment to supporting the development of and access to innovative radiopharmaceutical therapies around the globe."
Technology Platform and Future Prospects
Ratio Therapeutics (搜索) leverages its proprietary R&D platforms, Trillium™ and Macropa™, to develop fit-for-purpose heterobifunctional radiopharmaceuticals for therapy and imaging with pharmacokinetic modulation capabilities. These platforms are designed to improve drug availability, tumor delivery, and tumor loading, potentially enhancing therapeutic outcomes for cancer patients.
The company maintains manufacturing capabilities through its collaboration with PharmaLogic and its own state-of-the-art facility in Salt Lake City, Utah, ensuring reliable supply and quality in radiopharmaceutical production. This initiation marks the entry of Ratio's first therapeutic into clinical trials, representing a significant advancement in the company's mission to develop next-generation precision radiopharmaceuticals for solid tumors.