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

Core Viewpoint - Aptose Biosciences is advancing its clinical-stage drug tuspetinib (TUS) in a Phase 1/2 trial called TUSCANY, focusing on a triplet therapy for newly diagnosed acute myeloid leukemia (AML) patients who cannot receive induction chemotherapy, with recent data showing promising safety and efficacy results [1][3][6]. Group 1: Trial Progress and Results - The Cohort Safety Review Committee (CSRC) has approved escalating the dose of TUS from 40 mg to 80 mg based on favorable data from the initial four patients in the trial [1][2]. - No significant safety concerns or dose-limiting toxicities (DLTs) have been reported, with all four subjects in the 40 mg cohort remaining on study [2][6]. - The triplet therapy has shown complete responses (CRs) in difficult-to-treat AML patients, including those with TP53 mutations and FLT3-wildtype [6][7]. Group 2: Study Design and Objectives - The TUSCANY trial aims to test various doses of TUS in combination with standard doses of azacitidine (AZA) and venetoclax (VEN) for AML patients ineligible for induction chemotherapy [5][6]. - The trial is designed to create an improved frontline therapy that is active across diverse AML populations, durable, and well tolerated [4][5]. - Enrollment is ongoing, with 18-24 patients expected to be enrolled by mid-late 2025 [5][6]. Group 3: Drug Characteristics and Mechanism - Tuspetinib (TUS) is a convenient, once-daily oral agent administered in 28-day cycles, starting at 40 mg [5][6]. - Pharmacokinetic analyses indicate that TUS plasma levels are unaffected by the addition of AZA, ensuring predictability and avoiding dose alterations due to interactions [12]. - The triplet therapy is being developed to address unmet medical needs in oncology, particularly in hematology [9].