On October 29, 2021, the FDA granted accelerated approval to asciminib (Scemblix; Novartis) for the treatment of patients with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, previously treated with ≥2 tyrosine kinase inhibitors. The drug was also granted a full approval for the treatment of patients with Ph+ CML in chronic phase with a T315I mutation.
The approvals are based on the phase 3 ASCEMBL trial, which included patients with Ph+ CML in chronic phase who previously received ≥2 tyrosine kinase inhibitors, and the phase 1 CABL001X2101 trial, which included patients with Ph+ CML in chronic phase harboring a T315I mutation.
ASCEMBL included 233 patients randomized in a 2:1 ratio to receive asciminib at a twice-daily dose of 40 mg (N = 57) or bosutinib (Bosulif; Pfizer) at a once-daily dose of 500 mg (N = 76), with treatment continuing until intolerable toxicity or treatment failure.
At 24 weeks, the major molecular response (MMR) rate was 25% in the asciminib arm compared with 13% in the bosutinib arm. The complete cytogenetic response rates at 24 weeks were 41% and 24%, respectively. At 48 weeks, the MMR rate was 29% with asciminib versus 13% with bosutinib.
Forty-five patients enrolled in the multicenter, open-label CABL001X2101 trial were administered asciminib at a twice-daily dose of 200 mg, with treatment continuing until intolerable toxicity or treatment failure.
At 24 weeks, the MMR rate was 42% in patients treated with asciminib; this rate increased to 49% by 96 weeks.
The most common (≥20%) adverse events (AEs) with asciminib were upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities were decreased platelet counts, increased triglycerides, decreased neutrophil counts and hemoglobin, and increased creatine kinase, alanine aminotransferase, lipase, and amylase.
