Open-label, Phase I/II Study to Evaluate Safety and Efficacy of Asciminib With Chemotherapy Followed by Asciminib Plus Blinatumomab in Pediatric, Adolescent, and Young Adults With Relapsed or Refractory BCR::ABL1-positive (Philadelphia Positive, Ph+) or BCR::ABL1-like (Ph-like) ALL
Multi-center, open-label, single arm study of asciminib in participants aged ≥1 year to ≤30 years old with r/r Ph+ or ABL-class Ph-like ALL. This study will have 2 parts: Part 1 dose escalation and Part 2 dose expansion. Part 1 dose escalation will enroll participants aged ≥1 year to ≤30 years to determine the recommended phase 2 dose (RP2D) of asciminib when administered with low intensity chemotherapy. Part 2 dose expansion will enroll participants aged ≥1 year to ≤30 years to evaluate safety, tolerability, and efficacy of asciminib at the RP2D with the treatment regimen.
• Evidence of Ph+ ALL or ABL1 or ABL2 fusion Ph-like ALL, inclusive of participants with ABL1 T315I mutation
• Participants with CNS1, CNS2, CNS3a, or CNS3b at screening
• Active B-Cell ALL at screening defined by MFC or IG/TCR PCR of ALL blasts \>0.01% in participants with either:
‣ Primary refractory disease (\>0.01% ALL blasts present at the end of consolidation) OR
⁃ Relapsed ALL with evidence of involvement of BM with ALL (MFC or IG/TCR PCR \>0.01%) after at least one line of therapy
• Documented history of CD19 expressing B-cell ALL (in peripheral blood or bone marrow by flow cytometry).
• a) For participants who received anti-CD19 targeted therapy (e.g CD19 CAR T cells or blinatumomab), CD19 expressing B-cell ALL must be documented after anti-CD19 therapy completion prior to cycle 1 day 1
• Adequate hepatic and renal function (local laboratory analysis) as defined:
‣ ALT ≤ 5x upper limit of normal (ULN) for age
⁃ Total bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x ULN) for age, except for participants with Gilbert's syndrome who may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN
⁃ Estimated glomerular filtration rate (eGFR) using the Cockcroft-Gault formula in participants ≥ 18 years, OR radioisotope GFR ≥50 mL/min/1.73 m\^2, OR creatinine based on age and sex for participants \< 18 years old
• Adequate cardiac function defined as shortening fraction ≥27% by echocardiogram (ECHO) OR left ventricular ejection fraction of ≥50% by ECHO