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Race Oncology Ltd (ASX:RAC) has advanced the dose-escalation Phase 1b stage of the relapsed or refractory Acute Myeloid Leukaemia (R/R AML) trial running at the Chaim Sheba Medical Centre in Israel.
Encouraging clinical responses were observed in this very heavily pre-treated AML patient population, with three of the six patients bridged to a stem cell transplant.
Moving forward, The study led by Professor Arnon Nagler of the Chaim Sheba Medical Center will now advance to the Phase 2 efficacy stage, recruiting up to 17 patients.
“Modern AML setting”
Race CMO Dr David Fuller said: “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.
“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.”
Escalation stage – Phase one
Race has completed Phase 1b dose-escalation stage of the Phase 1b/2 Zantrene® (bisantrene dihydrochloride) study using a four-day treatment of Zantrene in combination with fludarabine and clofarabine.
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.
Study lead Prof Arnon Nagler said: “The encouraging results of our Phase 1 study with Zantrene monotherapy and moreover the current Phase 2 study altogether with Zantrene in combination in extremely heavily treated advanced high-risk AML patients are encouraging and may indicate a role for Zantrene in the modern AML treatment paradigm to the benefit of our patients.”
Efficacy stage – phase two
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 (one CR and two 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 for long-term remission.
The trial will now progress to the Phase 2 efficacy (expansion) stage using a four-day schedule of Zantrene in combination with fludarabine and clofarabine.
Race Clinical Advisory Board chair Prof Borje Andersson said: “We are very excited about the positive data from the first stage of this trial in such a heavily pre-treated R/R AML population, and we now look forward to the next phase, where we expect to see more patients respond favourably and with a consistently tolerable side-effect profile.
“It appears that bridging to transplantation with long-term disease control can be achieved with confidence, given we can since perceive that the side effects reverse within a few weeks of the course being completed.”
The Phase 2 stage of the trial is expected to take an additional 20 to 30 months to complete.
Given the trial is open-label, Race expects data will be reported at interim points throughout the remainder of the trial.
Published May 27 2022, Proactive