Mateon Therapeutics Reports Positive Phase 1/2 Study Results for Combretastatin A1 Plus Cytarabine in Adults with Relapsed Acute Myeloid Leukemia

Mateon Therapeutics Reports Positive Phase 12 Study Results for Combretastatin A1 Plus Cytarabine in Adults with Relapsed Acute Myeloid Leukemia

Mateon Therapeutics announced positive results from a phase 1/2 trial evaluating Combretastatin A1 (OXi4503) as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory Acute Myeloid Leukemia (AML). The trial met its primary endpoints of determining a maximum tolerated dose (phase 1b) and overall response rate (phase 2). 

Patients enrolled in the phase 1/2 trial, OXI1222, were treated by participating leukemia experts affiliated with the University of Florida, University of Kansas Cancer Center, David Geffen School of Medicine at UCLA, and University of Miami Sylvester Comprehensive Cancer Center, Miami. Data showed that adding combretastatin A1 to the standard chemotherapy drug cytarabine was generally well tolerated by AML patients and a maximum tolerated dose level of OXi4503 was identified as the recommended dose for further clinical development of this novel two-drug combination.  In 26 evaluable AML patients, there were 4 complete remissions (CR/CRi) and one partial remission (PR).  The CR responses were associated with >1-year overall survival times.  The combination therapy exhibited a manageable toxicity and a promising benefit to risk profile in older adults with relapsed AML.  Four of the 5 objective responders were in the ≥65-years poor prognosis age category with adverse cytogenetic features.

Results from the study will be presented at an upcoming medical meeting and discussed with health authorities, including the U.S. Food and Drug Administration (FDA). A peer-reviewed article detailing the clinical data was accepted for publication last Friday in the oncology journal Cancers (Basel).

OXi4503 has received orphan drug designation for AML in both the US and the European Union.  The FDA has also granted fast-track designation to OXi4503 for the treatment of relapsed/refractory AML. 

About Combretastatin A1 (OXi4503)

OXi4503 is cis-combretastatin A1 dipotassium diphosphate, a water-soluble prodrug of cis-combretastatin A1 (OXi4500), a naturally occurring derivative of the South African bush willow tree, Combretum caffrum, that reversibly binds tubulin at the colchicine binding site to inhibit microtubule assembly.  OXi4503 is a dual-function drug with vascular disrupting and cytotoxic properties that has exhibited single-agent anti-leukemia activity in animal models of AML and in a prior Phase 1A clinical study for relapsed/refractory (R/R) AML.

About Acute Myeloid Leukemia (AML)AML is the most common form of adult acute leukemia with >20,000 estimated new cases and >10,000 deaths in the United States (US) for 2019 (SEER Program, Despite recent advances in therapy, the five-year overall survival remains <30% and prognosis is grim in patients who experience a recurrence of their disease after first-line induction therapy, with <10% surviving five years after relapse.