Aptose Announces Positive Clinical Safety Review Committee (CSRC) Approval to Dose Escalate in Phase 1/2 Tuscany Trial of Frontline Triple Drug Therapy with Tuspetinib Amid Complete Responses and Favorable Safety in First Cohort
Aptose Biosciences (NASDAQ: APTO, TSX: APS) announced positive results from its Phase 1/2 TUSCANY trial, testing tuspetinib (TUS) in combination with venetoclax and azacitidine for newly diagnosed AML patients. The Clinical Safety Review Committee approved dose escalation from 40mg to 80mg TUS following favorable results from the first cohort.
Key findings from the initial 40mg cohort of four patients include: complete responses in difficult-to-treat TP53-mutated/CK AML and FLT3-wildtype AML patients, no dose-limiting toxicities, no prolonged myelosuppression, and no required dose reductions to standard-of-care components. Three FLT3-WT patients completed Cycle 1 with two achieving complete remissions. The fourth patient with FLT3-ITD and NPM1 mutations is still in Cycle 1.
The trial aims to enroll 18-24 patients by mid-late 2025, with multiple U.S. sites participating. Pharmacokinetic analyses showed TUS plasma levels were unaffected by AZA addition, and venetoclax levels remained consistent with previous studies.
Aptose Biosciences (NASDAQ: APTO, TSX: APS) ha annunciato risultati positivi dal suo trial di Fase 1/2 TUSCANY, che testa il tuspetinib (TUS) in combinazione con venetoclax e azacitidina per pazienti con AML recentemente diagnosticati. Il Comitato di Revisione della Sicurezza Clinica ha approvato l'aumento della dose da 40mg a 80mg di TUS dopo risultati favorevoli dalla prima coorte.
I risultati chiave della coorte iniziale di 40mg composta da quattro pazienti includono: risposte complete in pazienti con AML TP53-mutato/CK difficile da trattare e AML FLT3-wildtype, nessuna tossicità limitante la dose, nessuna mielosoppressione prolungata e nessuna riduzione necessaria delle dosi ai componenti standard di cura. Tre pazienti FLT3-WT hanno completato il Ciclo 1 con due che hanno raggiunto remissioni complete. Il quarto paziente con mutazioni FLT3-ITD e NPM1 è ancora nel Ciclo 1.
Il trial mira a reclutare 18-24 pazienti entro la metà-fine del 2025, con più siti negli Stati Uniti partecipanti. Le analisi farmacocinetiche hanno mostrato che i livelli plasmatici di TUS non sono stati influenzati dall'aggiunta di AZA e i livelli di venetoclax sono rimasti coerenti con studi precedenti.
Aptose Biosciences (NASDAQ: APTO, TSX: APS) anunció resultados positivos de su ensayo de Fase 1/2 TUSCANY, que prueba el tuspetinib (TUS) en combinación con venetoclax y azacitidina para pacientes con AML recién diagnosticados. El Comité de Revisión de Seguridad Clínica aprobó la escalación de dosis de 40mg a 80mg de TUS tras resultados favorables del primer grupo.
Los hallazgos clave del grupo inicial de 40mg, compuesto por cuatro pacientes, incluyen: respuestas completas en pacientes con AML TP53-mutada/CK difíciles de tratar y AML FLT3-wildtype, sin toxicidades limitantes de dosis, sin mielosupresión prolongada y sin reducciones de dosis necesarias en los componentes estándar de atención. Tres pacientes FLT3-WT completaron el Ciclo 1, con dos logrando remisiones completas. El cuarto paciente con mutaciones FLT3-ITD y NPM1 aún está en el Ciclo 1.
El ensayo tiene como objetivo reclutar de 18 a 24 pacientes para mediados o finales de 2025, con múltiples sitios en EE. UU. participando. Los análisis farmacocinéticos mostraron que los niveles plasmáticos de TUS no se vieron afectados por la adición de AZA, y los niveles de venetoclax se mantuvieron consistentes con estudios anteriores.
Aptose Biosciences (NASDAQ: APTO, TSX: APS)는 새로 진단된 AML 환자를 위한 venetoclax 및 azacitidine과 함께 tuspetinib (TUS)을 테스트하는 Phase 1/2 TUSCANY 시험에서 긍정적인 결과를 발표했습니다. 임상 안전성 검토 위원회는 첫 번째 코호트의 긍정적인 결과에 따라 TUS의 용량을 40mg에서 80mg으로 증가시키는 것을 승인했습니다.
40mg의 초기 코호트에서 네 명의 환자에 대한 주요 발견은 다음과 같습니다: 치료가 어려운 TP53 변이/CK AML 및 FLT3 야생형 AML 환자에서 완전 반응이 있었고, 용량 제한 독성이 없었으며, 지속적인 골수 억제가 없었고, 표준 치료 성분에 대한 용량 감소가 필요하지 않았습니다. 세 명의 FLT3-WT 환자가 Cycle 1을 완료했으며, 두 명은 완전 관해에 도달했습니다. FLT3-ITD 및 NPM1 변이를 가진 네 번째 환자는 아직 Cycle 1에 있습니다.
이 시험은 2025년 중반에서 후반까지 18-24명의 환자를 등록할 계획이며, 여러 미국 사이트가 참여하고 있습니다. 약리학적 분석 결과 TUS의 혈장 수준은 AZA 추가에 영향을 받지 않았으며, venetoclax의 수준은 이전 연구와 일관성을 유지했습니다.
Aptose Biosciences (NASDAQ: APTO, TSX: APS) a annoncé des résultats positifs de son essai de Phase 1/2 TUSCANY, testant le tuspetinib (TUS) en combinaison avec le venetoclax et l'azacitidine pour des patients atteints de LMA nouvellement diagnostiqués. Le Comité de Révision de la Sécurité Clinique a approuvé l'escalade de dose de 40 mg à 80 mg de TUS suite à des résultats favorables du premier groupe.
Les résultats clés du groupe initial de 40 mg composé de quatre patients comprennent : des réponses complètes chez des patients atteints de LMA TP53-mutée/CK difficiles à traiter et de LMA FLT3-wildtype, aucune toxicité limitante de la dose, aucune myélosuppression prolongée et aucune réduction de dose nécessaire pour les composants standards de soins. Trois patients FLT3-WT ont complété le Cycle 1, avec deux atteignant des rémissions complètes. Le quatrième patient avec des mutations FLT3-ITD et NPM1 est encore dans le Cycle 1.
L'essai vise à recruter 18 à 24 patients d'ici la mi-fin 2025, avec plusieurs sites aux États-Unis participant. Les analyses pharmacocinétiques ont montré que les niveaux plasmatiques de TUS n'étaient pas affectés par l'ajout d'AZA, et les niveaux de venetoclax sont restés cohérents avec les études précédentes.
Aptose Biosciences (NASDAQ: APTO, TSX: APS) hat positive Ergebnisse aus seiner Phase 1/2 TUSCANY-Studie bekannt gegeben, die tuspetinib (TUS) in Kombination mit venetoclax und azacitidine bei neu diagnostizierten AML-Patienten testet. Das Klinische Sicherheitsprüfungskomitee genehmigte die Dosissteigerung von 40mg auf 80mg TUS nach positiven Ergebnissen aus der ersten Kohorte.
Wichtige Ergebnisse aus der anfänglichen 40mg-Kohorte von vier Patienten umfassen: vollständige Ansprechen bei schwer zu behandelnden TP53-mutierten/CK AML und FLT3-Wildtyp-AML-Patienten, keine dosislimitierenden Toxizitäten, keine verlängerte Myelosuppression und keine erforderlichen Dosisreduktionen der Standardbehandlungskomponenten. Drei FLT3-WT-Patienten haben Zyklus 1 abgeschlossen, wobei zwei vollständige Remissionen erreichten. Der vierte Patient mit FLT3-ITD- und NPM1-Mutationen befindet sich noch in Zyklus 1.
Die Studie zielt darauf ab, bis Mitte bis Ende 2025 18-24 Patienten zu rekrutieren, wobei mehrere US-Standorte teilnehmen. Pharmakokinetische Analysen zeigten, dass die TUS-Plasmaspiegel durch die Hinzufügung von AZA nicht beeinträchtigt wurden und die Venetoclax-Spiegel konsistent mit früheren Studien blieben.
- Complete responses achieved in difficult-to-treat AML patients
- No dose-limiting toxicities or prolonged myelosuppression reported
- CSRC approval to escalate dosing from 40mg to 80mg
- Two out of three evaluable patients achieved complete remission by end of Cycle 1
- No drug interaction issues observed between TUS, venetoclax, and azacitidine
- Small initial patient cohort (only 4 patients)
- Trial completion timeline extends to mid-late 2025
Insights
The TUSCANY trial results represent a significant milestone in AML treatment development, particularly for difficult-to-treat patient populations. The achievement of complete responses, including an MRD-negative remission, in patients with TP53 mutations and complex karyotype is especially noteworthy, as these mutations typically indicate poor prognosis and treatment options.
Several key aspects make these results particularly compelling from a clinical and commercial perspective:
- The absence of prolonged myelosuppression and dose-limiting toxicities suggests a potentially superior safety profile compared to existing treatments, which often require dose reductions or treatment interruptions.
- The demonstration of efficacy in FLT3-wildtype patients expands the potential patient population beyond the more common targeted therapy approaches.
- The lack of pharmacokinetic interactions between tuspetinib and standard-of-care components (venetoclax and azacitidine) suggests a more predictable and manageable treatment regimen.
The planned enrollment of 18-24 patients by mid-late 2025 provides a clear timeline for additional data readouts. The CSRC's endorsement for dose escalation to 80mg indicates strong confidence in the safety profile and potentially sets the stage for improved efficacy at higher doses.
For investors, these early results suggest significant potential for tuspetinib to address current treatment gaps in frontline AML therapy. The ability to achieve complete responses in difficult-to-treat populations, combined with a favorable safety profile, could position tuspetinib as a preferred treatment option and drive substantial market adoption if approved.
- TUS+VEN+AZA triplet achieves complete responses (CRs) in difficult-to-treat TP53-mutated/CK AML and FLT3-wildtype AML patients, including a measurable residual disease (MRD) negative remission
- Dosing of initial 40 mg cohort complete; no prolonged myelosuppression or dose-limiting toxicities
- No dose reductions to the standard-of-care components of the regimen (AZA/VEN) in first cohort
- CSRC endorses escalation to 80 mg dosing, enrollment is open
SAN DIEGO and TORONTO, Feb. 20, 2025 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing the tuspetinib (TUS)-based triple drug frontline therapy to treat patients with newly diagnosed AML, today announced that the Cohort Safety Review Committee (CSRC) monitoring Aptose’s Phase 1/2 TUSCANY trial of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) has unanimously approved escalating from 40 mg TUS to 80 mg TUS based on its favorable review of data from the first four patients in the trial. 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.
No significant safety concerns or dose limiting toxicities (DLTs) have been reported, including no prolonged myelosuppression of subjects in remission. All four subjects treated in the 40 mg cohort remain on study while enrollment is open for the 80 mg cohort.
“With a high level of enthusiasm, our CSRC - comprised of study investigators that include key leaders in the development of therapeutic agents for AML - recommended we escalate dosing in our TUSCANY trial with tuspetinib,” said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. “The lack of prolonged myelosuppression with no DLT’s and several complete responses, including an MRD-negative CRh noted early in treatment, is truly encouraging. As one our chief investigators remarked, if the TUS+VEN+AZA triplet shows efficacy and tolerability in difficult-to-treat AML populations with little myelosuppression, tuspetinib could be a game changer for frontline AML treatment.”
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 40 mg 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.
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 TUS 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.
- Similarly, VEN plasma levels in Cycle 1 are consistent with published results and the prior TUS/VEN APTIVATE study in R/R AML, indicating no clinically significant interactions with TUS.
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
FAQ
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