Despite treatment advances in AML, including potentially curative allogeneic hematopoietic stem cell transplantation (HSCT), the cornerstone of AML induction chemotherapy continues to be variations of a treatment regimen known as "7 + 3", a seven-day infusion of cytarabine and a three-day administration of an anthracycline, an approach three decades old.
Many patients respond to this initial therapy, known as induction chemotherapy, which is generally followed by additional chemotherapy, known as consolidation therapy. A significant portion of patients ultimately relapse when the disease is renewed by a subpopulation of quiescent leukemic stem cells which lie dormant in the bone marrow stroma. This AML therapeutic regimen is associated with very significant short-term toxicity and with frequent development of life-threatening complications and occasional deaths during therapy.
Although targeted agents have contributed to the treatment of other blood disorders, thus far, they have failed to significantly improve survival for the great majority of people with AML. This is believed to be largely due to the heterogeneity of targets identified on AML cells. Agents under development which target specific mutations in leukemia cells, have shown some therapeutic activity, but only address a small percentage of those afflicted with this illness.
Significant evidence exists suggesting that leukemia stem cells utilize the same CXCL12/CXCR4 mechanism as normal hematopoietic stem cells to adhere to the protective bone marrow environment and maintain themselves in a protected, quiescent state. In pre-clinical models of AML, disrupting CXCL12/CXCR4 interaction inhibited leukemia cell survival and overcame chemotherapy resistance.
Cantex believes that CX-01 interrupts the CXCL12/CXCR4 axis by binding to both CXCL12 and CXCR4, disrupting the gradients responsible for their interaction. In addition, the Company believes that CX-01, through its binding to CXCR4, blocks internalization of the receptor, preventing the downstream intracellular signaling that supports leukemia cell resistance to cytotoxic chemotherapy.
Cantex has conducted an open-label, non-randomized Phase IIa pilot clinical trial of CX-01 in 12 patients with newly diagnosed AML. Of these 12 patients, 11 had no prior myelodysplastic syndrome, myeloproliferative disorder, or exposure to potentially leukemogenic therapies or agents. These 11 primary AML patients received CX-01 in combination with standard induction chemotherapy. All 11 patients achieved a complete response with a single cycle of this treatment. A 12th patient, with pre-existing chronic myelomonocytic leukemia, did not have a complete response with a single induction cycle, but achieved a complete remission with a second induction cycle without CX-01. These results suggest that CX-01 may enhance the complete remission rate in patients receiving chemotherapy for primary AML.
Cantex is now enrolling patients into a 160-patient, U.S.-based, multiple arm randomized Phase IIB clinical trial in 2016 in newly diagnosed patients with both primary and secondary AML, administering CX-01 in conjunction with the standard induction and consolidation chemotherapy. Endpoints of the clinical trial will include the effect of the addition of CX-01 to induction and consolidation chemotherapy on the incidence and duration of complete remission, on platelet and white blood cell recovery, and on overall survival. Cantex anticipates top-line results from this clinical trial in the second half of 2017.