On December 9, 2023 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, reported that a growing body of clinical data for Aptose’s lead compound tuspetinib (TUS), demonstrates significant benefit as a single agent and in combination with venetoclax (VEN) in patients with relapsed or refractory acute myeloid leukemia (R/R AML) in the ongoing APTIVATE Phase 1/2 study (Press release, Aptose Biosciences, DEC 9, 2023, View Source [SID1234638339]). Data were presented in an oral presentation today at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition by lead investigator Naval G. Daver, M.D., Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
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Tuspetinib is a once-daily, oral, precision targeted kinase inhibitor that suppresses select kinases that drive the proliferation of AML. These key kinase targets include the SYK, FLT3, JAK1/2, mutant forms of KIT, RSK2, and the TAK1-TAB1 kinases operative in AML, while avoiding non-therapeutic kinase targets to promote safety.
Dr. Daver reported data from more than 100 relapsed/refractory patients from multiple international clinical sites, who had failed prior therapy and then were treated with tuspetinib (TUS) as a single agent or tuspetinib in combination with venetoclax (TUS/VEN). TUS and TUS/VEN delivered multiple composite complete remissions (CRcs) in this very ill AML population, while maintaining a favorable safety profile across all treated patients.
"Tuspetinib is clearly an active and surprisingly well tolerated agent in one of the most challenging and heterogeneous disease settings in oncology – relapsed and refractory AML," said Dr. Daver. "Tuspetinib has demonstrated broad activity, including activity in patients with FLT3 wild-type AML (accounting for more than 70% of the AML population), FLT3 mutated AML, NPM1 mutated AML, as well as in patients with mutations historically associated with resistance to targeted therapy. Most notably, TUS targets VEN resistance mechanisms, enabling TUS/VEN uniquely to treat the very ill prior-VEN AML population, including both FLT3 mutant and FLT3 wildtype disease. From a broader perspective, the growing body of antileukemic activity, and continued favorable safety profile, support advancement of tuspetinib in a TUS/VEN/HMA triplet for the treatment of frontline newly diagnosed AML patients."
Dr. Daver also pointed out that while patients on the TUS/VEN therapy are early in their treatment cycles, most achieving a response remained on treatment and that responses have begun to mature as dosing continues.
Highlights of Dr. Daver’s ASH (Free ASH Whitepaper) oral presentation:
TUS as Single Agent
As a single agent at therapeutic doses of 80-160 mg in 68 evaluable patients, TUS was more active in VEN-naïve patients, with an overall CRc rate of 29% (8/28)
This included a 42% CRc rate (5/12) in FLT3-mutated patients
And a 19% CRc rate (3/16) in FLT3-unmutated, or wildtype, AML patients
Responses and blood counts improved with continuous dosing
Many bridged to an allogeneic stem cell transplant (HSCT)
Durability was observed when HSCT was not performed
80 mg was selected as the recommended phase 2 dose
Tuspetinib showed a favorable safety profile with only mild adverse events (AEs) and no dose-limiting toxicities (DLTs) up to 160 mg per day, and no drug discontinuations from drug related toxicity
TUS/VEN Combination Therapy
In the TUS/VEN doublet study, 49 patients were dosed with 80 mg of tuspetinib and 200 mg of venetoclax, with 36 evaluable (and 13 patients too early to assess)
Patients were heavily exposed to Prior-VEN and Prior-FLT3 inhibitor treatment
TUS/VEN was active in both VEN-naïve and prior Prior-VEN relapsed/refractory patients
TUS demonstrated composite complete remission (CRc) rates:
Among all evaluable patients, TUS/VEN demonstrated a CRc rate of 25% (9/36); 43% (3/7) in VEN-naïve patients, and 21% (6/29) in Prior-VEN patients.
Among FLT3 wildtype patients, TUS/VEN demonstrated an overall CRc rate of 20% (5/25); 33% (2/6) in VEN-naïve patients, and 16% (3/19) in Prior-VEN patients
Among FLT3 mutant patients, TUS/VEN demonstrated an overall CRc rate of 36% (4/11); a complete response in a VEN-naïve patient (1/1); a 30% (3/10) in Prior-VEN patients; and 44% (4/9) in patients treated prior with a FLT3 inhibitor
Key findings:
TUS/VEN is a well tolerated combination therapy
TUS/VEN is active across broad populations of R/R AML
TUS/VEN is active in FLT3 wildtype, representing ~70% of AML patients
TUS/VEN retains activity in the difficult-to-treat Prior-VEN AML population
"The wealth of data we have generated – and continue to generate – on tuspetinib points to a highly active, well-differentiated drug for AML populations that are in need of options beyond currently available therapies," said Rafael Bejar, M.D., Ph.D., Chief Medical Officer at Aptose. "Brisk patient enrollment in our APTIVATE trial has led to a fast-growing database that includes many more patients at various stages of treatment. We look forward to reporting our next set of data in the first quarter of 2024."
The slides from Dr. Daver’s presentation are available on Aptose’s website here.