Final results from Race Oncology Ltd (ASX:RAC, OTC:RAONF)'s Phase 1b/2 trial of bisantrene (RC110) for relapsed or refractory acute myeloid leukaemia (R/R AML) have been published in the British Journal of Haematology, confirming clinical benefit in patients with advanced disease.
Conducted at Israel’s Chaim Sheba Medical Centre under the supervision of Professor Arnon Nagler, the investigator-led study assessed a combination of bisantrene with clofarabine and fludarabine (Bis/Clo/Flu). The paper is titled “Bisantrene in combination with fludarabine and clofarabine as salvage therapy for adult patients with refractory or relapsed acute myeloid leukaemia (AML) — an open-label, phase I/II study” (doi:10.1111/bjh.70035).
Among patients with highly advanced disease, 40% responded to treatment with the Bis/Clo/Flu regimen — comprising five complete responses and one partial response — surpassing the trial’s predefined efficacy threshold of at least three complete responses. Notably, one patient remains alive and disease-free more than two years after receiving treatment.
“I would like to extend my sincere thanks to Professor Nagler and his dedicated team at the Chaim Sheba Medical Centre, who have spent the last 6 years meticulously investigating the utility of bisantrene for patients with relapsed/refractory Acute Myeloid Leukaemia. The Sheba team’s dedication and commitment has added to the strong historical evidence of the efficacy of bisantrene in treating patients with AML,” Race Oncology CEO Dr Daniel Tillett said.
“We extend our gratitude to all patients and their families whose participation make the development of new AML treatments such as bisantrene possible.”
Trial design
The open-label Phase 1b/2 study enrolled adult patients with R/R AML to evaluate the safety and efficacy of the Bis/Clo/Flu regimen administered intravenously. The Phase 1b stage used a standard 3+3 dose-escalation design to establish the recommended Phase 2 dose (RP2D), progressing from a four-day regimen in Cohort 1 to a five-day schedule in Cohort 2.
The Phase 2 expansion phase followed a two-stage Simon design. Of the first nine patients treated, at least one achieved a complete response, allowing the study to proceed. The efficacy endpoint was met when three or more complete responses were observed among the final cohort.
Study results confirm strong response rate in relapsed AML patients
Six of the 15 evaluable patients (40%) in the Phase 2 efficacy stage of the trial demonstrated a clinical response to the combination therapy of bisantrene, clofarabine, and fludarabine (Bis/Clo/Flu). This included five complete responses and one partial response, with three of the responders presenting with active extramedullary disease.
Five of the six responders were successfully bridged to a potentially curative stem cell transplant within one to three months post-treatment. Of these five, three have since passed away — one due to graft-versus-host disease at Day 45 post-transplant, one from disease relapse four months after transplant, and one from infection on Day 610 post-treatment. One patient remains alive and disease-free more than two years after receiving Bis/Clo/Flu therapy.
The complete response rate met the prespecified Simon two-stage efficacy threshold, which required at least three complete responses to warrant further study.
These interim findings were presented at the 65th American Society of Hematology (ASH) Annual Conference held from 9–12 December 2023.
The results build on outcomes from an earlier Phase 2 RC110 bisantrene monotherapy trial in patients with relapsed or refractory acute myeloid leukaemia (R/R AML), and collectively support the continued clinical development of bisantrene in future AML studies.