Nov 2021: Asciminib (Scemblix, Novartis AG) was given accelerated approval by the Food and Drug Administration for patients with Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in chronic phase (CP) who had previously received two or more tyrosine kinase inhibitors (TKIs), as well as for adult patients with Ph+ CML in CP who had the T315I mutation.
ASCEMBL (NCT03106779) is a multi-center, randomised, active-controlled, open-label clinical trial investigating asciminib in patients with Ph+ CML in CP who have had two or more TKIs before. A total of 233 patients were randomly assigned (2:1) to receive either asciminib 40 mg twice daily or bosutinib 500 mg once daily, based on their significant cytogenetic response (MCyR) status. Patients were kept on treatment until they experienced intolerable toxicity or treatment failure. At 24 weeks, the main efficacy outcome measure was the major molecular response (MMR). The MMR rate in patients treated with asciminib was 25% (95 percent CI: 19, 33) compared to 13% (95 percent CI: 6.5, 23; p=0.029) in those treated with bosutinib. The median length of MMR has not yet been attained, with a median follow-up of 20 months.
Asciminib is being tested in patients with Ph+ CML in CP with the T315I mutation in CABL001X2101 (NCT02081378), a multi-center, open-label clinical investigation. The efficacy of asciminib 200 mg twice daily in 45 patients with the T315I mutation was studied. Patients were kept on treatment until they experienced intolerable toxicity or treatment failure. MMR was the primary effectiveness outcome measure. MMR was reached in 42 percent (19/45, 95 percent confidence interval: 28 percent to 58 percent) of the patients after 24 weeks. MMR was reached in 49 percent of patients (22/45, 95 percent confidence interval: 34 percent to 64 percent) after 96 weeks. The average treatment time was 108 weeks (range, 2 to 215 weeks).
Upper respiratory tract infections, musculoskeletal pain, weariness, nausea, rash, and diarrhoea are the most prevalent side effects (20%). Decreased platelet counts, increased triglycerides, decreased neutrophil counts and haemoglobin, and elevated creatine kinase, alanine aminotransferase, lipase, and amylase are the most prevalent laboratory abnormalities.
In patients with Ph+ CML in CP who have previously been treated with two or more TKIs, the recommended asciminib dose is 80 mg administered orally once day at around the same time each day or 40 mg twice daily at approximately 12-hour intervals. In patients with Ph+ CML in CP with the T315I mutation, the suggested asciminib dose is 200 mg twice day at approximately 12-hour intervals.