- TUS Monotherapy and TUS+Venetoclax (VEN) Doublet Therapy Show Broad Clinical Activity and Strong Safety Data in relapsed or refractory (R/R) Acute Myeloid Leukemia (AML) and Differentiate TUS from other Investigational Drugs in AML
- TUS Monotherapy and TUS+VEN Doublet Therapy Active in Difficult-to-treat Genetic Subgroups, FLT3 Wildtype AML
- TUS Shown to Target VEN Resistance Mechanisms and Retain Activity on VEN-Resistant AML Cells in Preclinical Study
- TUS+VEN+Azacitidine (AZA) Triplet Trial to Treat Newly Diagnosed AML Patients; Clinical Sites Being Activated
Tuspetinib (TUS) is being developed as a TUS + venetoclax (VEN) + hypomethylating agent (HMA) triple drug combination (or TUS+VEN+HMA triplet) as frontline therapy for newly diagnosed AML patients. Aptose’s poster presentation illustrates the safety and breadth of activity of TUS monotherapy and the TUS+VEN doublet combination in relapsed or refractory (R/R) AML patients from the APTIVATE Phase 1/2 trial and supports the launch of the TUS+VEN+HMA (using azacitidine, AZA, as the HMA) triplet frontline therapy in newly diagnosed AML patients. Tuspetinib, a convenient once daily oral agent that potently targets SYK, FLT3, mutated KIT, JAK1/2, and RSK2 kinases, avoids many typical toxicity concerns observed with other agents. In the APTIVATE trial, TUS achieved broad activity across AML patients with a diversity of adverse genetics as a single agent and in combination with venetoclax in a very ill and heavily pre-treated AML population. Blast reductions and objective responses were observed in patients with prior-VEN, prior-FLT3 inhibitor (FLT3i) and prior-HSCT therapies, those with highly adverse genetics - including mutations in TP53 and RAS genes, and those with mutated or unmutated (wildtype) FLT3 genes.
“Our APTIVATE trial of tuspetinib as a monotherapy and in combination treatment with venetoclax in a very ill AML patient population, has yielded excellent, consistent safety and demonstrated clinical activity across a broad range of AML – including many with highly adverse genetic mutations,” said
TITLE: Safety and Efficacy of Tuspetinib as Monotherapy and Combined with Venetoclax in a Phase 1/2 Trial of Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (EHA ID # P557)
CONCLUSIONS
- Extensive dose exploration with TUS (93 patients) and TUS+VEN (79 patients) in highly treatment experienced R/R AML patients (prior VEN, FLT3i, HMA, chemotherapy, HSCT)
- TUS monotherapy
- Complete remissions achieved at 40, 80, 120, and 160 mg with no DLT
- 42% CRc and 50% ORR was observed in VEN naïve and FLT3-mutation harboring patients.
- Responses achieved in patients harboring highly adverse genetics (TP53MUT, RASMUT, other)
- TUS+VEN Doublet
- Remains safe and well tolerated (40mg TUS + 400mg VEN | 80mg TUS + 400mg VEN)
- Achieves bone marrow blast reductions and responses among diverse R/R AML patients with
adverse mutations and prior failure of VEN
- TUS targets known VEN resistance mechanisms in vitro and is clinically active in both FLT3MUT & FLT3WT R/R AML populations even after prior VEN exposure.
AML 1L UNMET NEED AND TUS+VEN+HMA TRIPLET
Significant Unmet Medical Need in Frontline Newly Diagnosed AML
- Progress made with VEN+HMA in 1L therapy but 1/3 do not respond and median OS <15 months with <25% alive at 3-years.
- Response rates and OS need improvement, especially in adverse genetic subgroups
- Emergence of VEN resistance via RAS/MAPK, TP53, and FLT3 clonal expansion, among other mechanisms, compromises salvage therapies in R/R setting
- A 3rd agent is needed to boost responses with VEN+HMA standard of care therapy
TUS is Ideal 3rd Agent for Addition to VEN+AZA to Treat Newly Diagnosed AML
- TUS has excellent safety alone and in combination with VEN when co-administered
- TUS has broad activity across genetic subgroups including TP53, RAS/MAPK, & FLT3 mutants
- TUS mechanism may minimize drug resistance to VEN via inhibition of key AML kinases
- TUS can be administered with or without food allowing co-administration with VEN
- Preliminary PK data suggest no clinically meaningful interaction between TUS and VEN requiring dose modification for co-administration.
In addition, a separate preclinical abstract was published as an e-poster publication at EHA:
TITLE: Tuspetinib Retains Nanomolar Potency Against AML Cells Engineered to Express the NRAS G12D Mutation or Selected for Resistance to Venetoclax (EHA ePoster ID # P1756).
The study demonstrated that TUS targets known venetoclax (VEN) resistance mechanisms, retaining nanomolar potency against AML cells engineered to express the NRAS-G12D mutation or selected for resistance to VEN, and in combination with VEN, could prevent emergence of resistance to both agents. TUS resistant cells showed hypersensitivity to VEN such that treatment with both drugs could also interfere with the emergence of TUS resistance.
To see the full poster presentations, please visit Aptose’s website:
https://www.aptose.com/investors/company-information/presentations
About Aptose
Forward Looking Statements
This press release may contain forward-looking statements within the meaning of Canadian and
Should one or more of these risks or uncertainties materialize, or should the assumptions set out in the section entitled "Risk Factors" in our filings with Canadian securities regulators and the
For further information, please contact: | |
617-430-7576 | |
201-923-2049 | Daniel@LifeSciAdvisors.com |
spietropaolo@aptose.com |
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