On December 23, 2019 Mateon Therapeutics Inc. (OTCQB:MATN), dedicated to the development of innovative treatments for cancer, reported that the multi-institutional OXI1222 study in people with previously treated relapsed acute myeloid leukemia (AML) met its primary endpoint (Press release, Mateon Therapeutics, DEC 23, 2019, View Source [SID1234552601]).

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Patients 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. This trial was registered at www.clinicaltrials.gov as NCT02576301.

The study showed that adding Mateon’s lead anti-AML drug Combretastatin A1, also known as OXi4503, 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. The safety, feasibility, and early clinical activity of this new treatment in R/R AML deserves further clinical validation in a randomized registration study. 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).

"This work emphasizes our commitment to advance our investigational drug OXi4503 which shows clinical impact potential to address unmet needs in relapsed/recurrent hematologic malignancies, especially AML," stated Dr. Vuong Trieu, Chairman and Chief Executive Officer of Mateon Therapeutics.

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

"The greatest challenge in AML is relapsed or refractory disease. For relapsed or refractory AML, there is no consensus on a single re-induction regimen. By combining OXi4503 with the standard chemotherapy drug cytarabine, we hope to develop an innovative approach that improves outcomes for patients with relapsed AML, especially those who are older and have a dismal prognosis," explained Fatih Uckun, M.D., Ph.D., Chief Medical Officer of Mateon Therapeutics.

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, www.seer.cancer.gov). 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. There is an urgent need for effective new treatment strategies for relapsed AML. Therefore, clinical development of new therapies has been the focal point of AML research over the last decade.

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. Notably, the combination of OXi4503 with cytarabine in xenografted human AML models was more effective than either drug alone. The clinical safety profile of OXi4503 as a single agent has previously been evaluated in Phase 1A clinical trials. In the NCT00977210 Phase 1 dose-finding study in 43 advanced solid tumor patients, OXi4503 doses were escalated from 0.06 to 15.4 mg/m2, and 8.5 mg/m2 was defined as the MTD. In the NCT01085656 Phase 1A trial designed to evaluate the safety profile, MTD, and recommended Phase 2 dose (RP2D) of OXi4503 in patients with R/R AML and MDS, a total of 18 patients were treated with single agent OXi4503 and showed a manageable safety profile at single-agent dose levels up to of 7.81 mg/m2. There was early evidence of possible single-agent activity as one relapsed AML patient treated at the 2.5 mg/m2 dose level achieved a CRi. The primary purpose of the present multicenter Phase 1B study was to define the maximum tolerated dose and safety profile of OXi4503 and cytarabine administered in combination (OXA) in patients with relapsed/refractory R/R AML.