On October 29, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the kinase inhibitor asciminib (Scemblix) for patients with Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in chronic phase who have been previously treated with two or more tyrosine kinase inhibitors. The FDA also approved asciminib for adult patients with Ph+ CML in chronic phase with a T315I mutation.
ASCEMBL and CABL001X2101 Trials
ASCEMBL, a multicenter, randomized, active-controlled, open-label clinical trial, is evaluating asciminib in patients with Ph+ CML in chronic phase who were previously treated with two or more tyrosine kinase inhibitors. A total of 233 patients were randomly assigned 2:1 and stratified according to major cytogenetic response status to receive either asciminib at 40 mg twice daily or bosutinib at 500 mg once daily. Patients continued treatment until unacceptable toxicity or treatment failure occurred.
The main efficacy outcome measure of ASCEMBL was major molecular response at 24 weeks. The major molecular response rate was 25% (95% confidence interval [CI] = 19%–33%) in patients treated with asciminib compared with 13% (95% CI = 6.5%–23%, P = .029) in those receiving bosutinib. With a median follow-up duration of 20 months, the median duration of major molecular response has not yet been reached.
CABL001X2101, a multicenter, open-label clinical trial, is evaluating asciminib in patients with Ph+ CML in chronic phase who also have a T315I mutation. Efficacy was based on 45 patients with the T315I mutation who received asciminib at 200 mg twice daily. Patients continued treatment until unacceptable toxicity or treatment failure occurred.
The main efficacy outcome measure of CABL001X2101 was major molecular response, which was achieved by 24 weeks in 42% (19 of 45, 95% CI = 28%–58%) of the patients. Major molecular response was achieved by 96 weeks in 49% (22 of 45, 95% CI = 34%–64%) of the patients. The median duration of treatment was 108 weeks (range = 2–215).
The most commonly reported adverse reactions (≥ 20%) were upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities included decreased platelet counts; increased triglycerides; decreased neutrophil counts and hemoglobin; and increased creatine kinase, alanine aminotransferase, lipase, and amylase.
The recommended asciminib dose in patients with Ph+ CML in chronic phase who have been previously treated with two or more tyrosine kinase inhibitors is 80 mg taken orally once daily at approximately the same time each day or 40 mg twice daily at approximately 12-hour intervals. The recommended asciminib dose in patients with Ph+ CML in chronic phase with a T315I mutation is 200 mg taken orally twice daily at approximately 12-hour intervals.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 4 months ahead of the FDA goal date.
This application was granted Priority Review, Breakthrough Therapy designations, Fast Track designation, and Orphan Drug designation.