On November 7, 2023 Race Oncology (ASX:RAC) reported positive interim clinical results from an ongoing investigator-initiated Phase II study of its core asset bisantrene in combination with fludarabine and clofarabine in R/R AML patients (Press release, Race Oncology, NOV 7, 2023, View Source [SID1234637060]).

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The trial abstract has been peer-reviewed and the interim results selected for presentation at the prestigious American Society of Hematology (ASH) (Free ASH Whitepaper) 65th Annual Conference in December.

The oral poster presentation titled Bisantrene in combination with fludarabine and clofarabine as salvage therapy for adult patients with relapsed or refractory acute myeloid leukemia (AML) – an open-label, phase II study describes clinical results from the first 15 evaluable patients treated on study since August 2021.

Bisantrene is a unique product that is a small molecule, anthracene-based chemotherapeutic that has anti-cancer benefits but additionally reduced cardiotoxicity, meaning it is less likely to cause heart dysfunction.

In combination with fludarabine and clofarabine, bisantrene administered over four days induced a clinical response in 6 of 15 evaluable patients (40%) with a median age of 48 (range 19-69) with advanced (R/R AML).

Five of the six treatment-responsive patients were well enough to receive a potentially curative bone marrow transplant within one to three months of treatment.

Of the five-bone marrow transplanted patients, three have since died with one from graft-versus-host disease, another relapsed within four months of transplant, and the third from infection after two years. The two other patients remain disease free and in complete remission.

Palliative patients responding ‘quite frankly amazing’
RAC executive director Dr Pete Smith says AML patients who fail many lines of treatment are likely to be only offered palliative care as many clinicians believe the risks of using more experimental treatments exceed the chance of the patient responding.

He says many clinicians would consider even a single patient being able to be bridged to a bone marrow transplant a success in such a heavily pre-treated population.

"This is a patient group that normally would not be treated in Australia and clinicians would have given up by now," Smith says.

"They have failed an average of four lines of therapy, so they tried some drug or drug combination then maybe had a response but stopped responding then went on something else."

Smith says outlook for the patients in the trial without treatment was "dire" with a life expectancy measured in weeks if they do not receive efficacious treatment.

He says to take this patient population and put them on the bisantrene drug combination and see it relatively well tolerated and 40% responding with five having a complete response is "quite frankly amazing".

‘Very encouraging results in younger AML patients’
The trial is running at the Sheba Medical Centre in Israel, under the supervision of key opinion leader Professor Arnon Nagler.

"These rather impressive results in such a heavily pre-treated population support further studies of bisantrene-based combinations, including those with venetoclax or hypomethylating agents," Nagler says in the trial abstract.

Calvary Mater Newcastle and John Hunter Hospitals director of haematology Professor Dr Anoop Enjeti, who was not involved in the study, says it "produced very encouraging results in younger AML patients".

"Many of these patients achieved a complete or a partial remission, enabling a significant proportion to go on to a bone marrow transplant," he says.

"These impressive results provide proof of concept supporting further trials of bisantrene in combination with other AML treatments to improve outcomes for this leukaemia."

Moving bisantrene into less advanced AML patients
Smith says the positive trial data will help progress bisantrene as a treatment for patients that are more likely to respond.

"All new oncology drugs and drug combinations start out in the hardest to treat patients with the most advanced disease.

"As clinical understanding grows around a drug’s efficacy and side-effects, clinicians will start to use the drug in earlier-stage patients who are more likely to respond to treatment."

Furthermore, he says the positive clinical trial data is the foundation of commercialisation or partnership discussions with large pharmaceutical companies.

"Race continues to engage with potential pharma partners and will update the market on progress when appropriate," he says.

"It’s still early days in terms of digesting this data and working out the path forward but very encouraging."