Race Oncology Ltd (ASX:RAC) has signed a clinical trial collaboration and supply agreement with Astex Pharmaceuticals (NASDAQ:ASTX), Inc, a subsidiary of Otsuka Pharmaceutical of Japan, to supply ASTX727 (oral decitabine and cedazuridine) for a clinical trial of Zantrene®, RAC-006.
Notably, the agreement provides ASTX727 for a clinical trial by Race Oncology for the treatment of patients with extramedullary AML and high-risk MDS.
Under the terms of the agreement, Astexwill provide ASTX727 free of charge to RAC which includes initial shipment to nominated supply depots for use in Australia, Italy, Spain, Germany and the USA.
RAC-006 is the first clinical trial in the world to investigate the targeting of Fatso/Fat mass and obesity-associated (FTO) protein as a potential cancer treatment.
Moving forward, Race and Astex will also enter into a separate safety data exchange agreement (SDEA) to facilitate pharmacovigilance reporting requirements.
Cancer pipeline
Race Oncology’s phase 2/3 cancer drug Zantrene is a potent inhibitor of the FTO protein.
Notably, overexpression of FTO has been shown to be the genetic driver of a diverse range of cancers including AML.
ASTX727 is an orally administered, fixed-dose combination of the approved anti-cancer DNA hypomethylating agent, decitabine, together with cedazuridine, an inhibitor of cytidine deaminase (CDA).
By inhibiting CDA in the gut and the liver, ASTX727 is designed to allow for oral delivery of decitabine and is given daily for five days in a 28-day cycle.
Consequently, Race has generated preclinical data indicating that dosing Zantrene in combination with decitabine showed significantly greater cell killing across a genetically diverse panel of AML cell lines than either drug on its own.
Race chief executive officer Phillip Lynch said, “We are pleased to enter into this important collaboration with Astex and wish to thank them for their interest and support of this clinical trial targeting FTO using the novel combination of ASTX727 and low dose bisantrene in AML and high-risk MDS patients unfit for high-intensity chemotherapy."
Clinical trial design
This open label Phase two trial will recruit up to 60 patients with 18F-FDG PET/CT imaging identified extramedullary AML at 10 clinical sites using a two-stratum (arm) design.
The first stratum will utilise Zantrene as a high dose, single agent, treatment over seven days in patients with extramedullary AML who are able to tolerate high-intensity chemotherapy, followed by one or more cycles of consolidation treatment of Zantrene in combination with Ara-C, a standard of care drug.
The second stratum will use Zantrene as a low dose FTO-targeted agent in combination with the oral hypomethylating agent ASTX727, for MDS/AML patients unwilling or unable to tolerate high-intensity chemotherapy.
The primary endpoint will be complete response (CR) and complete response with incomplete haematological recovery (CRi) with an aim of bridging to an allogeneic hematopoietic stem cell transplant (Stratum 1), or safety and tolerability (Stratum 2).
Key secondary endpoints include safety and tolerability of Zantrene in combination with AraC or ASTX727, overall and event-free survival, and FTO expression or other biomarkers with response to treatment.