ASC4Kids-2: Asciminib in pediatric chronic myeloid leukemia with or without T315I.

Abstract

TPS6606 Background: Adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib, nilotinib, and bosutinib, are the standard of care for pediatric patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP), with efficacy and safety profiles generally comparable to those observed in adults. However, TKIs can cause long-term adverse effects in pediatric pts, including delayed growth and development. Effective therapies that minimize long-term adverse effects in pediatric pts are needed. No TKI is approved for pediatric pts with the T315I mutation, which is linked with lower progression-free and overall survival. Asciminib represents an alternative to ATP-competitive TKIs that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP). Asciminib is approved for adults with newly diagnosed and previously treated CML-CP (at 80 mg daily), and those harboring T315I (at 200 mg twice daily). In ASC4Kids (NCT04925479), asciminib was well-tolerated and efficacious in pediatric pts resistant or intolerant (R/I) to 1 prior TKI without T315I. Here, we describe ASC4Kids-2 (NCT07354074), a phase 2 study evaluating asciminib in pediatric pts with CML-CP. Methods: Approximately 50 pediatric pts aged 1 to <18 years with Philadelphia chromosome positive (Ph+) CML-CP who are (1) newly diagnosed without known T315I, (2) R/I to ≥1 prior TKI without known T315I, or (3) with T315I irrespective of prior TKIs, will be enrolled in this multicenter, open-label, single-arm study. Asciminib will be administered at 80 mg once daily, or at 200 mg twice daily for pts with T315I using the adult formulation under fasting conditions, or as a body weight–based pediatric formulation (2.6 mg/kg once daily or 6.5 mg/kg twice daily for pts with T315I, rounded to the nearest 5 mg) in the fed state. ASC4Kids-2 consists of a 22-day screening period followed by a treatment period with visits at weeks 1, 2, 4, 8, 12, 24, 36, and 48, then every 12 weeks. A posttreatment follow-up period includes a 30-day safety follow-up call and survival assessments every 12 weeks until study end, which is 240 weeks after the last pt receives the first dose. The primary objective is to assess treatment efficacy via MMR at week 48 (defined as the proportion of pts who meet MMR criteria at week 48, excluding those who discontinued earlier or lost response at/before week 48). Secondary endpoints include MMR at week 96; hematologic, cytogenetic, and molecular responses at and by scheduled time points; time to response, progression, or treatment failure; duration of response; event-free and overall survival; growth and sexual maturation (assessed via height, weight, bone age measured by x-ray, and Tanner staging); safety; and pharmacokinetic parameters. Clinical trial information: NCT04925479 .