On June 14, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, reported a clinical poster presentation and a preclinical e-poster at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress in Madrid, Spain (Press release, Aptose Biosciences, JUN 14, 2024, View Source [SID1234644329]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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 Rafael Bejar, M.D., Ph.D., Corresponding Author and Chief Medical Officer of Aptose. "The AML treatment paradigm is quickly shifting to combination therapy for newly diagnosed AML patients, but current triplet therapies in development are limited by toxicities and are aimed at narrow subpopulations, leaving them unable to treat the larger AML population. Tuspetinib, with demonstrated broad activity and favorable safety/tolerability profile, appears to be an ideal third agent to add to a venetoclax and hypomethylating agent regimen. We and our clinical investigators are eager to initiate dosing of the TUS+VEN+AZA triplet study."
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 (Free EHA Whitepaper):
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:
View Source