APTO - Aptose Presents Highlights from Clinical Update Webcast Featuring Latest Available Data on AML Drug Tuspetinib | Benzinga
- Tuspetinib (TUS) Combination with Venetoclax (VEN) Clinical Findings Highlighted
- TUS Targets VEN Resistance Mechanisms to Re-sensitize VEN Failure Patients to VEN
- 44% ORR with TUS/VEN in Difficult-to-Treat VEN Failure R/R AML Patients
- 48% ORR with TUS/VEN in Heavily Pre-treated R/R AML Patients
- Consistent Favorable Safety with TUS Single Agent and TUS/VEN Doublet
SAN DIEGO and TORONTO, Oct. 30, 2023 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ:APTO, TSX:APS), a clinical-stage precision oncology company developing highly differentiated oral kinase inhibitors to treat hematologic malignancies, released highlights from a clinical update event held today, October 30, 2023, in conjunction with the European School of Haematology (ESH) 6th International Conference: Acute Myeloid Leukemia "Molecular and Translational": Advances in Biology and Treatment, being held in Estoril, Portugal (the "ESH 2023 Conference").
The webcast event featured a comprehensive review of up-to-date clinical data for Aptose's lead compound tuspetinib (TUS) by Rafael Bejar, MD, PhD, Aptose's Chief Medical Officer, and featured Naval G. Daver, MD, Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Dr. Daver is the lead investigator on Aptose's APTIVATE trial of tuspetinib and is recognized for significant achievements in the development of novel acute myeloid leukemia (AML) treatments, including several combination therapies.
Tuspetinib (TUS) 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 other kinases are avoided to promote safety.
AML care has shifted toward venetoclax (VEN) containing combination regimens and a new population of difficult-to-treat VEN relapsed patients ("VEN failures") is emerging. Tuspetinib's safety, activity, mechanism of action, and convenient dosing make it ideal for combination therapy. Importantly, TUS directly targets VEN resistance mechanisms (suppresses mutated FLT3, mutated KIT, SYK and mutated JAK1/2 of the JAK/STAT pathway, RSK2 of the RAS/MAPK pathway, key oncogenic growth and proliferation signals, and MCL-1 expression). This means that TUS targets pathways and may lead to re-sensitizing VEN-resistant cells to VEN when given in combination. TUS/VEN may safely and successfully treat these VEN failures, as we already have observed clinically, and an accelerated approval path may be available for VEN failure relapsed or refractory (R/R) AML patients treated with TUS/VEN.
"We are really pleased by our growing safety and efficacy data on tuspetinib in very difficult-to-treat AML patient populations," said Dr. Bejar. "This includes activity in FLT3-unmutated patients, a population that accounts for more than 70% of AML and has few effective treatment options. Additionally, tuspetinib's significant activity in patients who have failed venetoclax treatment – a rapidly-emerging population of particularly high unmet medical need – provides a clear development pathway for tuspetinib with the potential for accelerated approval."
"The safety and efficacy data we've seen with the tuspetinib/venetoclax combination is very encouraging, suggesting that tuspetinib may effectively treat the large number of VEN failures we are seeing frequently in our clinics," said Dr. Daver. "Data from the TUS/VEN doublet gives us confidence to move tuspetinib forward into a TUS/VEN/HMA triplet for the treatment of frontline newly-diagnosed AML patients. Tuspetinib is an exciting agent, and I am happy to be part of the clinical development team."
Clinical Findings
Aptose provided updated clinical findings from the ongoing APTIVATE study of tuspetinib:
Patient Enrollment
- More than 140 patients have been treated with tuspetinib to date
- 91 patients have received TUS as a single agent
- Aptose anticipated dosing up to 30 patients with TUS/VEN by the ESH 2023 Conference; however, investigator enthusiasm resulted in dosing of 49 patients (as of October 23, 2023), and patients continue being enrolled
Safety Profile
In the most recent data cut (October 23, 2023), the favorable safety profile remained consistent for TUS and TUS/VEN treated R/R AML patients:
- No TUS related adverse events (AEs) of QTc prolongation
- No observed differentiation syndrome
- No TUS related non-hematologic serious AEs
- No TUS related deaths
- No rhabdomyolysis or AEs of elevated creatine phosphokinase (CPK)
- No TUS related dose-limiting toxicities (DLT) from 20 mg level through 160 mg level
- One DLT of muscle weakness at 200 mg
- Occurred in patient with high exposure
- Not rhabdomyolysis ? No muscle destruction
- Avoids many typical toxicities observed with other FLT3, IDH1/2, and menin inhibitors
- In TUS/VEN doublet, no unexpected or new safety signals were observed
Tuspetinib Single Agent
- Tuspetinib as a single agent was well-tolerated and highly active among relapsed or refractory (R/R) AML patients with a diversity of adverse genotypes. TUS ...