Pharmacokinetics and Safety of Asciminib (ASC) in Pediatric Patients (pts) with Philadelphia Chromosome-Positive (ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the ASC4KIDS Study.

6562 Background: For pediatric pts with Ph+ CML-CP, treatment options with improved efficacy and long-term safety are needed. ASC is a first-in-class tyrosine kinase inhibitor (TKI) Specifically Targeting the ABL Myristoyl Pocket (STAMP), approved for adults with Ph+ CML-CP treated with ≥2 prior TKIs. The phase Ib/II ASC4KIDS study (NCT04925479) aims to characterize the pharmacokinetics (PK) and long-term safety profile of ASC in pediatric pts. Methods: This multi-center, open-label study included pts aged 1–<18 years (yrs) with Ph+ CML-CP, without T315I mutation, treated with ≥1 prior TKIs. The primary endpoint is to characterize the PK of ASC in pediatric pts and identify a dose using the pediatric formulation (PF, taken with food) leading to an ASC exposure comparable to the adult dose and formulation (AF, 40 mg tablet twice daily [BID] fasted). Secondary endpoints include safety, molecular responses and acceptability/palatability of the pediatric formulation. In an exploratory group, pts 14‒<18 yrs old were treated with the AF (fasted). In study Part 1 (dose-determining cohort), pts received PF at an initial dose of 1.3 mg/kg BID (with food) to assess ASC exposure (measured by area under the curve from dosing to the time of the last measured concentration [AUClast] and maximum plasma concentration [Cmax]) and safety. In Part 2 (dose expansion cohort), additional pts will be treated with the dose confirmed in Part 1 (across Part 1 + Part 2; 10 pts per age group: 1‒<12 yrs and 12‒<18 yrs, for a total of 20 pts). In Part 3, another 10 pts will be enrolled (5 pts per age group), who will receive the same total ASC dose as a once daily regimen. Results: 4 and 9 pts were enrolled in the Part 1 AF and PF groups, respectively. At interim data cutoff (03-Aug-2023), all pts were receiving ongoing treatment. Age ranges were 15‒16 yrs (AF group) and 2‒16 yrs (PF group). Averaged ASC exposure in the AF group was comparable to that observed in adults. 3/4 (75.0%) pts on ASC AF experienced adverse events (AEs); none were Grade ≥3. There were no new safety signals as compared to the known safety profile of ASC in adults. Averaged ASC exposure in the PF group was comparable to that observed in adults (median AUClast: 5051 vs 5130 hr*ng/mL; median Cmax: 711 vs 939 ng/mL, respectively). Based on these data, the PF dose of 1.3 mg/kg BID (with food) was confirmed as the pediatric dose. All pts on ASC PF experienced AEs; Grade ≥3 AEs were reported for 2/9 pts (22.2%). No predefined dose-limiting toxicities, serious AEs, or AEs leading to discontinuation were reported in either group. Conclusions: ASC exposure with the PF (with food) in pediatric pts was comparable to that of adult pts treated with ASC 40 mg BID (fasted); the confirmed PF dose of 1.3 mg/kg BID will continue to be tested in Part 2 of the study. ASC was safe and well tolerated in pediatric pts. Clinical trial information: NCT04925479 .