Race Oncology Limited (ASX:RAC) has confirmed a dose escalation Phase 1b stage of the relapsed or refractory Acute Myeloid Leukaemia (R/R AML) trial running at the Chaim Sheba Medical Centre, Israel has successfully completed after the treatment of the first six patients.
The six patients were heavily pre-treated and had received a median of four prior lines of AML treatment (range two to eight).
By design, the primary endpoint of the initial phase of this two-stage clinical trial is establishing the recommended dose to be used in the subsequent Phase 2 expansion (efficacy) stage.
This first stage requires identifying the treatment dose level that achieves two or fewer dose-limiting toxicities (DLTs) from six consecutively treated patients. In the initial six patients treated, two DLTs were reported (one Grade 3 elevated liver enzymes and one Grade 5 infection).
Both DLTs occurred in the most heavily pre-treated patients who had received five and eight prior lines of treatment, respectively.
Efficacy results in this refractory patient population were very encouraging, with one patient showing a complete response (CR) based on morphology, two patients having a partial response (PR) including one with extramedullary disease, two showing no response (NR), and one patient not assessable (NA) due to death from infection.
Infection is a known side effect of all intensive chemotherapeutic regimens and is one of the leading causes of death in AML patients. Three patients (1 CR and 2 PR) were bridged to an allogeneic stem cell transplant.
Bridging a patient to transplant is an important positive outcome in AML treatment as it offers the patient the potential of long-term remission. Of note, these three patients had all received less than five prior lines of treatment.
Poor or no response to known efficacious treatments is common and expected in heavily pre-treated cancer patients.
The trial will now progress to the Phase 2 efficacy (expansion) stage using a four-day schedule of Zantrene (bisantrene dihydrochloride) in combination with fludarabine and clofarabine.
The positive results from the first stage of this trial in such a heavily pre-treated relapsed or refractory Acute Myeloid Leukaemia population is encouraging, especially with three of the patients being subsequently bridged to transplant,” Race CMO, Dr David Fuller, said.
“We look forward to the next stage of this study which, together with data from the EMD AML Trial (RAC-006) which is soon to commence recruitment in Australia, is extending our understanding of Zantrene in a modern AML setting.”
Relapsed or Refractory Acute Myeloid Leukemia Primary refractory or relapsed AML is associated with poor prognosis and remains a serious therapeutic challenge.
Primary refractory AML is defined by the absence of CR, manifested by blast count of ≥5% in bone marrow after one or two cycles of intense induction chemotherapy.
Up to 30% of adults with newly diagnosed AML fail to achieve CR after two courses of intensive chemotherapy. Even when CR is achieved through intense chemotherapy, approximately half of the younger and 80% of the older patients, relapse. In both clinical situations, refractory and/or relapsed AML, active disease remains a major therapeutic challenge despite recent advances in the clinic.
