Aptose’s Frontline Triple Drug Therapy with Tuspetinib Achieves Notable Responses in Newly Diagnosed AML Patients in the Phase 1/2 TUSCANY Trial
Aptose Biosciences (NASDAQ: APTO, TSX: APS) reported promising early results from its Phase 1/2 TUSCANY trial testing tuspetinib in combination with venetoclax and azacitidine (TUS+VEN+AZA triplet) for newly diagnosed acute myeloid leukemia (AML) patients.
Key findings from the first cohort of four patients receiving the lowest dose (40mg) include:
- Two FLT3-wildtype patients achieved complete remissions by end of Cycle 1
- One patient with biallelic TP53 mutations achieved complete remission
- One patient showed significant reduction in bone marrow leukemic blasts
- The fourth patient with FLT3-ITD and NPM1 mutations is still in Cycle 1
The treatment showed favorable safety with no dose-limiting toxicities or dose adjustments needed. The TUSCANY trial aims to enroll 18-24 patients by mid-late 2025, testing various doses of tuspetinib with standard dosing of venetoclax and azacitidine.
Aptose Biosciences (NASDAQ: APTO, TSX: APS) ha riportato risultati promettenti dai primi risultati del suo trial Fase 1/2 TUSCANY, che testa il tuspetinib in combinazione con venetoclax e azacitidina (triplet TUS+VEN+AZA) per pazienti con leucemia mieloide acuta (AML) recentemente diagnosticata.
I principali risultati del primo gruppo di quattro pazienti che hanno ricevuto la dose più bassa (40 mg) includono:
- Due pazienti FLT3-wildtype hanno raggiunto remissioni complete entro la fine del Ciclo 1
- Un paziente con mutazioni bialleliche di TP53 ha raggiunto la remissione completa
- Un paziente ha mostrato una significativa riduzione dei blast leucemici nel midollo osseo
- Il quarto paziente con mutazioni FLT3-ITD e NPM1 è ancora nel Ciclo 1
Il trattamento ha mostrato una sicurezza favorevole, senza tossicità limitanti per la dose o necessità di aggiustamenti della dose. Il trial TUSCANY mira a reclutare 18-24 pazienti entro la metà-fine del 2025, testando varie dosi di tuspetinib con dosaggi standard di venetoclax e azacitidina.
Aptose Biosciences (NASDAQ: APTO, TSX: APS) informó resultados prometedores de los primeros resultados de su ensayo Fase 1/2 TUSCANY, que prueba el tuspetinib en combinación con venetoclax y azacitidina (triple TUS+VEN+AZA) para pacientes recién diagnosticados con leucemia mieloide aguda (LMA).
Los hallazgos clave del primer grupo de cuatro pacientes que recibieron la dosis más baja (40 mg) incluyen:
- Dos pacientes FLT3-wildtype lograron remisiones completas al final del Ciclo 1
- Un paciente con mutaciones bialélicas de TP53 logró remisión completa
- Un paciente mostró una reducción significativa en los blastos leucémicos en la médula ósea
- El cuarto paciente con mutaciones FLT3-ITD y NPM1 todavía está en el Ciclo 1
El tratamiento mostró una seguridad favorable, sin toxicidades limitantes de dosis ni necesidad de ajustes de dosis. El ensayo TUSCANY tiene como objetivo inscribir a 18-24 pacientes para mediados-fines de 2025, probando varias dosis de tuspetinib con dosis estándar de venetoclax y azacitidina.
Aptose Biosciences (NASDAQ: APTO, TSX: APS)는 최근 진단된 급성 골수성 백혈병(AML) 환자를 위해 venetoclax와 azacitidine(트리플 TUS+VEN+AZA)와 함께 tuspetinib을 시험하는 1/2상 TUSCANY 시험의 초기 유망 결과를 보고했습니다.
가장 낮은 용량(40mg)을 받은 첫 번째 그룹의 네 명의 환자에서 주요 발견은 다음과 같습니다:
- 두 명의 FLT3-wildtype 환자가 1주기 종료 시점에 완전 관해를 달성했습니다.
- TP53의 이형접합체 돌연변이를 가진 한 환자가 완전 관해를 달성했습니다.
- 한 환자가 골수 백혈병 세포의 유의미한 감소를 보였습니다.
- FLT3-ITD 및 NPM1 돌연변이를 가진 네 번째 환자는 아직 1주기에 있습니다.
치료는 안전성이 우수하며 용량 제한 독성이나 용량 조정이 필요하지 않았습니다. TUSCANY 시험은 2025년 중반-말까지 18-24명의 환자를 등록할 계획이며, tuspetinib의 다양한 용량을 venetoclax와 azacitidine의 표준 용량과 함께 시험할 예정입니다.
Aptose Biosciences (NASDAQ: APTO, TSX: APS) a rapporté des résultats préliminaires prometteurs de son essai de Phase 1/2 TUSCANY testant le tuspetinib en combinaison avec le venetoclax et l'azacitidine (triple TUS+VEN+AZA) pour des patients nouvellement diagnostiqués avec une leucémie myéloïde aiguë (LMA).
Les résultats clés du premier groupe de quatre patients recevant la dose la plus basse (40 mg) incluent:
- Deux patients FLT3-wildtype ont atteint des remissions complètes à la fin du Cycle 1
- Un patient avec des mutations bialléliques de TP53 a atteint une remission complète
- Un patient a montré une réduction significative des blastes leucémiques dans la moelle osseuse
- Le quatrième patient avec des mutations FLT3-ITD et NPM1 est encore au Cycle 1
Le traitement a montré une sécurité favorable, sans toxicités limitantes de dose ni ajustements de dose nécessaires. L'essai TUSCANY vise à recruter 18-24 patients d'ici la mi-fin 2025, en testant diverses doses de tuspetinib avec des doses standard de venetoclax et d'azacitidine.
Aptose Biosciences (NASDAQ: APTO, TSX: APS) berichtete über vielversprechende frühe Ergebnisse aus seiner Phase 1/2 TUSCANY-Studie, die tuspetinib in Kombination mit venetoclax und azacitidin (TUS+VEN+AZA-Triplett) bei neu diagnostizierten Patienten mit akuter myeloischer Leukämie (AML) testet.
Die wichtigsten Ergebnisse aus der ersten Kohorte von vier Patienten, die die niedrigste Dosis (40 mg) erhielten, umfassen:
- Zwei FLT3-wildtyp Patienten erreichten bis zum Ende des Zyklus 1 vollständige Remissionen
- Ein Patient mit biallelischen TP53-Mutationen erreichte eine vollständige Remission
- Ein Patient zeigte eine signifikante Reduktion der leukämischen Blasten im Knochenmark
- Der vierte Patient mit FLT3-ITD- und NPM1-Mutationen befindet sich noch im Zyklus 1
Die Behandlung zeigte eine günstige Sicherheit ohne dosisbegrenzende Toxizität oder notwendige Dosisanpassungen. Die TUSCANY-Studie zielt darauf ab, bis Mitte bis Ende 2025 18-24 Patienten zu rekrutieren und verschiedene Dosen von tuspetinib mit der Standarddosis von venetoclax und azacitidin zu testen.
- Complete remission achieved in TP53-mutated patient, a traditionally difficult-to-treat form of AML
- No dose-limiting toxicities observed in first cohort
- Pharmacokinetic levels remain stable with combination therapy
- Two out of three evaluable patients achieved complete remission in Cycle 1
- Small patient sample size (only 4 patients) in early trial phase
- Results are preliminary and require further validation
Insights
The early results from Aptose's TUSCANY trial represent a potentially significant advancement in AML treatment, particularly noteworthy for several key reasons:
- The achievement of complete remission in a patient with biallelic TP53 mutations and complex karyotype is particularly remarkable. TP53-mutated AML typically has a dismal prognosis with current therapies, with median survival often measured in months. Achieving complete remission in cycle 1 for this patient population could represent a major therapeutic breakthrough.
- The trial demonstrates efficacy in FLT3-wildtype patients, with 2 out of 3 evaluable patients achieving complete remissions (CR/CRh) in the first cycle. This is significant because FLT3-wildtype represents approximately 75% of AML cases, suggesting broad market potential.
- The favorable safety profile without dose-limiting toxicities and the ability to maintain standard dosing of venetoclax and azacitidine is crucial. Many combination therapies require dose reductions due to toxicity or drug interactions, which can compromise efficacy. The maintenance of consistent pharmacokinetic levels suggests optimal drug exposure without the need for complex dose adjustments.
From a market perspective, tuspetinib's potential ability to treat diverse AML populations, including traditionally difficult-to-treat mutations, positions it uniquely in the competitive landscape. The planned enrollment of 18-24 patients by mid-late 2025 suggests a relatively rapid development timeline, which could accelerate market entry if positive results continue.
However, it's important to note that these are early results from just four patients at the lowest dose level (40mg). While promising, larger patient numbers and longer follow-up will be needed to confirm these initial findings. The planned dose escalation could potentially reveal even greater efficacy at higher doses, though safety will need to be carefully monitored.
TUS+VEN+AZA triplet achieves Cycle 1 complete remission (CR) in TP53-mutated/CK AML
TUS+VEN+AZA triplet achieves Cycle 1 complete remissions in FLT3-wildtype AML patients
TUS+VEN+AZA triplet shows favorable safety with no alteration of VEN and AZA dosing
PK levels of TUS in the triplet remain equivalent to levels as TUS or TUS+VEN therapy
SAN DIEGO and TORONTO, Feb. 12, 2025 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company, today reported promising early safety and response results from newly diagnosed acute myeloid leukemia (AML) patients dosed in Aptose’s Phase 1/2 TUSCANY trial with a 40 mg dose of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet). The TUS+VEN+AZA triplet is being developed as a frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy.
In January 2025, Aptose announced the initiation of the TUSCANY trial and dosing in the first cohort of newly-diagnosed AML patients with the lowest starting dose (40 mg) of TUS as part of the TUS+VEN+AZA triplet, and the early data reveal promising clinical safety and antileukemic activity.
- To date, four newly diagnosed AML patients have received the lowest dose of TUS (40 mg) as part of the (TUS+VEN+AZA) combination.
- Three patients with unmutated (wildtype) FLT3 (FLT3-WT) completed Cycle 1 of treatment with no dose-limiting toxicities (DLTs) and no dose adjustments.
- Two FLT3-WT patients achieved complete remissions (CR and CRh) by the end of Cycle 1.
- Notably, a patient with biallelic TP53 mutations and a complex karyotype obtained CR.
- The third FLT3-WT patient experienced significant reductions in bone marrow leukemic blasts during Cycle 1 and remains on therapy in Cycle 2.
- The fourth patient, harboring FLT3-ITD and NPM1 mutations, is currently dosing in Cycle 1 and is not yet eligible for response evaluation
- Pharmacokinetic (PK) analyses for TUS show plasma levels unaffected by the addition of AZA, providing predictability and avoiding the need for dose alterations due to PK interactions.
“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,” said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. “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. With enrollment ongoing in the TUSCANY study, we look forward to reporting additional data as it becomes available.”
“TUS+VEN+AZA triplet therapy has the potential to treat large AML patient populations, including those with traditionally difficult-to-treat mutations, and improve patient outcomes right from the outset of treatment,” said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. 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.”
TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study
Tuspetinib based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Responses to TUS were also observed in those with prior-VEN and prior-FLT3 inhibitor (FLT3i) therapies, those with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes.
The TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS will be administered in 28-day cycles, beginning at 40mg once daily, with dose escalations planned after a safety review of each dose level. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-late 2025. Data will be released as it becomes available.
More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov (here).
About Aptose
Aptose Biosciences is a clinical-stage biotechnology company committed to developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The Company’s lead clinical-stage, oral kinase inhibitor tuspetinib (TUS) has demonstrated activity as a monotherapy and in combination therapy in patients with relapsed or refractory acute myeloid leukemia (AML) and is being developed as a frontline triplet therapy in newly diagnosed AML. For more information, please visit www.aptose.com.
Forward Looking Statements
This press release may contain forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements relating to the therapeutic potential and safety profile of tuspetinib (including the triplet therapy) and its clinical development, the anticipated enrollment rate in the TUSCANY trial and the timing thereof, as well as statements relating to the Company’s plans, objectives, expectations and intentions and other statements including words such as “continue”, “expect”, “intend”, “will”, “should”, “would”, “may”, and other similar expressions. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by us are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance or achievements described in this press release. Such factors could include, among others: our ability to obtain the capital required for research and operations and to continue as a going concern; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market conditions; inability of new manufacturers to produce acceptable batches of GMP in sufficient quantities; unexpected manufacturing defects; and other risks detailed from time-to-time in our ongoing quarterly filings, annual information forms, annual reports and annual filings with Canadian securities regulators and the United States Securities and Exchange Commission.
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 United States Securities and Exchange Commission underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this press release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by law. We cannot assure you that such statements will prove to be accurate as actual results and future events could differ materially from those anticipated in such statements. Investors are cautioned that forward-looking statements are not guarantees of future performance and accordingly investors are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty therein.
For further information, please contact:
Aptose Biosciences Inc.
Susan Pietropaolo
Corporate Communications & Investor Relations
201-923-2049
spietropaolo@aptose.com
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