ASCIMINIB TAB

Clinical Criteria Summary

Previous treatment failure or intolerance of at least two other tyrosine kinase inhibitors (TKI)
Presence of T315I gatekeeper mutation, previous treatment failure or intolerance to at least one other TKI, and not a candidate for ponatinib
Patients who may not be candidates for ponatinib include those with established coronary artery disease, limb-threatening peripheral vascular disease, history of TIA and/or CVA; consider risk vs. benefit

For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 week after stopping treatment
Avoid lactation/breastfeeding during therapy and for 1 week after stopping treatment

Adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) who have received prior treatment with 2 or more tyrosine kinase inhibitors (TKIs)
Adult patients with Ph+ CML-CP who have the T315I mutation of BCR-ABL1

Tablets available in 20 mg and 40 mg strengths
For Ph+ CML after ≥2 prior TKIs: 80 mg orally once daily or 40 mg orally twice daily
For Ph+ CML with T315I mutation: 200 mg orally twice daily
Administer without food; avoid food at least 2 hours before or 1 hour after dosing

Complete blood count labs every two weeks for three months, followed by monthly labs
Serum amylase and lipase levels monthly
Blood pressure monitoring throughout treatment
Assessment of cardiovascular risk factors throughout treatment

Contraindicated in patients with known A337T, P465S, or F359V/I/C mutations
Myelosuppression (thrombocytopenia, neutropenia, anemia): May need to hold or adjust dose based on severity and occurrence
Pancreatic toxicity (pancreatitis, elevated pancreatic enzymes): May need to hold, adjust dose, or discontinue based on severity
Hypertension: May need to hold, adjust dose, or discontinue based on severity
Hypersensitivity reactions: May need to hold, adjust dose, or discontinue based on severity
Cardiovascular toxicity (cardiac dysfunction, arrhythmias, cardiac failure): May need to hold, adjust dose, or discontinue based on severity
Embryo-fetal toxicity: Avoid in pregnancy; implement effective contraception during and one week following treatment for women of child-bearing potential
Lactation: Advise women to avoid breastfeeding during and one week after end of treatment
No boxed warnings

Strong CYP3A4 inhibitors: Monitor closely when used with 200 mg twice daily dosing
Itraconazole (solution containing hydroxypropyl-β-cyclodextrin): Avoid concomitant use at all recommended doses
CYP3A4 substrates: Monitor closely with 80 mg once daily; avoid concomitant use with 200 mg twice daily
CYP2C9 substrates: Avoid concomitant use at all recommended doses
P-gp substrates: Monitor concomitant use at all recommended doses

Renal impairment: None required for estimated glomerular filtration rate (eGFR) of 15-89 mL/min/1.73 m2 without dialysis
Hepatic impairment: None required

FDA indications include Ph+ CML-CP in patients previously treated with at least 2 TKIs or presence of T315I mutation
NCCN Clinical Practice Guidelines recommend as a Category 2A treatment option for patients with treatment failure to at least 2 previous TKIs or the presence of the T315I mutation
Considered for use in Ph+ CML-CP patients after at least two other TKI treatments or presence of the T315I gatekeeper mutation, alongside clinical judgment in selection of next-line TKI therapy