Tuspetinib as part of triple-combo therapy showing potential in AML
Clinical trial ongoing in newly diagnosed adults not eligible for induction chemo
A triple-combination therapy using tuspetinib, Aptose Biosciences‘ experimental oral therapy, is showing potential in treating adults with newly diagnosed acute myeloid leukemia (AML), a rare and usually aggressive type of blood cancer.
That’s according to data from the first four AML patients treated in the global Phase 1/2 TUSCANY clinical trial (NCT03850574), which is testing tuspetinib in combination with two approved blood cancer therapies: venetoclax (sold as Venclexta) and azacitidine (sold as ). The triple-combination treatment is abbreviated as TUS+VEN+AZA.
“These are very promising early results from the TUSCANY trial of TUS+VEN+AZA and the first indicators of the safety and efficacy we expected to see in newly diagnosed AML patients,” Rafael Bejar, MD, PhD, Aptose’s chief medical officer, said in a company press release.
Newly diagnosed AML patients not eligible for induction chemo in study
Adults with newly diagnosed AML in the TUSCANY study, still enrolling in the U.S., are not eligible for induction chemotherapy. Of note, induction chemotherapy is an initial and intensive blood cancer treatment phase that involves administering a combination of strong chemotherapy drugs to kill as many cancer cells as possible.
All four treated patients received tuspetinib at a dose of 40 mg per day, in addition to venetoclax and azacitidine at their approved dosing schedules.
Three of these adults have completed the first 28-day cycle of treatment. All three were wild-type FLT3, meaning the FLT3 gene, which is sometimes mutated in AML, was not mutated in these participants. FLT3 mutations are the most frequent genetic alterations in AML and possibly associated with a more aggressive disease course, as they can lead to increased growth and resistance to standard chemotherapy.
To date, no side effects suggesting that the tested dose of tuspetinib is too high to be reasonably used as a medication have been reported. The oral therapy acts to block the activity of multiple kinases — enzymes that are involved in cellular signaling and growth, whose abnormal activity often helps to drive the atypical cell growth that causes cancer.
Pharmacological data so far suggest that levels of azacitidine do not affect levels of tuspetinib in a patient’s bloodstream. According to Aptose, these findings, if confirmed, should help to simplify dosing, as it would not need adjusting for the effects of drug interactions.
“The ability to treat such diverse AML populations — including FLT3 wildtype patients — with a favorable safety profile and without having to alter the standard of care dosing, differentiates our drug from many AML drugs in development,” said William G. Rice, PhD, Aptose’s chairman, president, and CEO.
2 of 3 adults achieve complete remission after first treatment cycle
Two of the four patients achieved complete remission after the first cycle of treatment, meaning they have no detectable cancer. One complete remission patient carried mutations in the TP53 gene; these mutations are often linked with more aggressive cancer.
“To achieve a complete remission (CR) in Cycle 1 in a subject harboring a TP53 mutation — one of the most adverse forms of AML — is particularly encouraging,” Bejar said.
The third patient, who did not achieve complete remission after finishing the first cycle, was reported to show a notable decrease in signs of cancer cells after that cycle. This patient is continuing treatment in a second cycle.
The fourth adult, who carries mutations in the FLT3 gene, is undergoing dosing in the first cycle and does not yet have data available for evaluation, the company reported.
The TUSCANY study is continuing to recruit adults, ages 18 to 75, newly diagnosed with AML and ineligible to receive intensive chemotherapy at sites across the U.S. Sites in Australia, Germany, New Zealand, Spain, and Korea are active but no longer enrolling.
“With enrollment ongoing in the TUSCANY study, we look forward to reporting additional data as it becomes available,” Bejar said.
Tuspetinib was originally discovered by Hanmi Pharmaceutical; Aptose took over development of the program in 2022.
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