AUTHORS
Jessica A. Pollard I, MD, Hiroyuki Shimada2, Matthias Hoch3, Vishal Dhamal4, Nithya Agrawal5, Ana Paula Paula Torres Cardoso, MD, PhD6, Masakatsu Yanagimachi7, Ho Joon Im, MD, PhD8, Markus Metzler, MD, PhD9, Nobuko Hijiya, MD10
AFFILIATIONS
1 Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, United States, Harvard Medical School, Boston, MA, United States
2 Keio University School of Medicine, Tokyo, Japan
3 Novartis Institute for BioMedical Research, Basel, Switzerland
4 Novartis Healthcare Private Limited, Mumbai, India
5 Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States
6 Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States
7 Kanagawa Children's Medical Center, Yokohama, Japan
8 Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea, Rep. of South
9 Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany
10 Pediatric Hematology, Columbia University Irving Medical Center, New York, NY, United States
ABSTRACT
Introduction: Imatinib and second-generation tyrosine kinase inhibitors (2G TKIs; dasatinib, nilotinib, bosutinib) are approved for pediatric CML-CP, demonstrating efficacy and safety comparable to that in adults. Despite achievement of near-normal survival with TKI therapy in patients with CML, prolonged exposure to these agents can cause long-term adverse events (AEs) in pediatric patients during development, including growth retardation. Furthermore, poorer outcomes with second-line 2G TKIs in pediatric patients resistant or intolerant to prior therapy highlight the need for effective treatments that minimize long-term AEs after first-line failure.
The phase 1b/2 ASC4Kids study (NCT04925479) evaluates pharmacokinetics, safety, and efficacy of asciminib in pediatric patients with Philadelphia chromosome positive CML-CP without the T315I mutation who were previously treated with ≥1 TKI. A prespecified interim analysis in 9 patients (cutoff, August 3, 2023) confirmed that 1.3 mg/kg twice daily (BID) under fed conditions provided target exposures comparable to adults in the phase 3 ASCEMBL study (NCT03106779). A second prespecified interim analysis in 28 patients receiving asciminib pediatric formulation (cutoff, July 15, 2025), reported no AE-related discontinuations, stable height percentiles in most patients, and generally stable BCR::ABL1IS through week 104.
The current primary analysis will further characterize the pharmacokinetics and safety profile of asciminib pediatric formulation 1.3 mg/kg BID (fed) in pediatric patients and assess efficacy to support clinical activity.
Methods: ASC4Kids has 3 parts (enrollment is complete for 1 and 2 and ongoing for 3): Part 1 determined dose by characterizing pharmacokinetics with body weight–adjusted BID dosing under fed conditions and identified a pediatric formulation dose achieving exposure comparable to adults receiving asciminib 40 mg BID (adult formulation; fasted); Part 2 target enrollment was ≥10 patients per age group (1 to <12 years and 12 to <18 years), including patients enrolled in Part 1, to assess pharmacokinetics, safety, and efficacy with the confirmed asciminib pediatric formulation 1.3 mg/kg BID (fed); and Part 3, is currently enrolling 5 additional patients per age group (10 patients total) to evaluate asciminib pediatric formulation 2.6 mg/kg once daily (QD; fed). An exploratory cohort aged 14 to <18 years receiving asciminib adult formulation 40 mg BID (fasted) was also included. Enrollment to this cohort was closed when the pediatric formulation became available.
Results: The ASC4Kids primary analysis, conducted after the last patient receiving asciminib pediatric formulation in Parts 1 and 2 completes ≥52 of treatment (cutoff, June 16, 2026), will be presented at ASH 2026 and will include cumulative pharmacokinetics, safety, and efficacy data from 37 patients: 28 receiving asciminib pediatric formulation 1.3 mg/kg BID in Parts 1 and 2, and 9 receiving asciminib pediatric formulation 2.6 mg/kg QD in Part 3. Additional data from 4 patients receiving asciminib adult formulation in the exploratory cohort will be included.
Conclusions: A previously presented interim analysis of asciminib pediatric formulation 1.3 mg/kg BID (fed) showed pharmacokinetics comparable to those observed in adults, favorable safety and tolerability, and stable molecular responses. The primary analysis of ASC4Kids will further characterize longer-term safety and efficacy outcomes with asciminib pediatric formulation 1.3 mg/kg BID (fed) and provide preliminary pharmacokinetic data from Part 3 with asciminib pediatric formulation 2.6 mg/kg QD.
DISCLOSURES
Jessica A. Pollard I, MD: Syndax Pharmaceuticals - Consultancy (Includes expert testimony)