FDA Grants Accelerated Approval to Asciminib for Ph+ CML in Chronic Phase

FDA

The FDA has granted an accelerated approval to asciminib (Scemblix) for patients with Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase who have previously been treated with 2 or more TKIs. The regulatory agency also granted a full approval for the use of the agent in those with Ph-positive CML in chronic phase with a T315I mutation.¹

The regulatory decisions were supported by data from the phase 3 ASCEMBL trial (NCT03106779), which evaluated the agent in patients with Ph-positive CML who previously received 2 or more TKIs, and the phase 1 CABL001X2101 trial (NCT02081378), which evaluated its use in patients with Ph-positive CML in chronic chase harboring a T315I mutation.

“CML can be difficult to treat when currently available treatments fail patients, when treatment side effects cannot be tolerated, or sometimes both,” expressed Michael J. Mauro, MD, hematologist and Myeloproliferative Neoplasms Program leader at Memorial Sloan Kettering Cancer Center, stated in a press release.² “The addition of Scemblix into the CML treatment landscape gives us a novel approach to combat this blood cancer, helping address clinical challenges in patients struggling after switching to a second treatment, as well as in patients who develop the T315I mutation and face significantly worse outcomes.”

ASCEMBL enrolled a total of 233 patients, who were randomized 2:1 to receive either asciminib at a twice-daily dose of 40 mg (n = 157) or bosutinib (Bosulif) at a once-daily dose of 500 mg (n = 76). Patients were stratified based on major cytogenetic response status, and treatment was continued until intolerable toxicity or treatment failure.

The median age of participants was 52 years (range, 19-83), with 19% of patients aged 65 years or older and 2.6% of patients aged 75 years or older. Moreover, 52% of patients were female, 75% were White, and 81% had an ECOG performance status of 0. Notably, 48% of patients received 2 prior lines of treatment, 31% received 3 prior lines, 15% received 4 prior lines, and 6% received 5 or more prior lines. The median duration of treatment was 67 weeks (range, 0.1-162) in those who were given asciminib vs 30 weeks in those who received bosutinib.

Results from the trial demonstrated that asciminib elicited a molecular response (MMR) rate of 25% (95% CI, 19%-33%) at 24 weeks vs 13% (95% CI, 6.5%-23%) with bosutinib in this patient population (95% CI, 2.2%-22%; P = .029). The complete cytogenetic responses elicited at 24 weeks in the investigative and control arms were 41% (95% CI, 31%-51%) and 24% (95% CI, 14%-37%), respectively.

At 48 weeks, the MMR rate was 29% (95% CI, 22%-37%) in those who received asciminib vs 13% (95% CI, 6.5%-23%) in those who received bosutinib. At a median follow-up of 20 months (range, 1 day to 36 months), the median duration of response had not yet been reached with MMR at any time.

Regarding safety, the number of patients who discontinued treatment because of toxicities was found to be three times lower with asciminib vs bosutinib, at 7% and 25%, respectively.

The most frequently reported adverse effects in the asciminib arm included upper respiratory tract infections and musculoskeletal pain; a decrease in platelet and neutrophil counts, a decrease in hemoglobin; and an increase in triglycerides, creatine kinase and alanine aminotransferase.

A total of 45 patients were enrolled to CABL001X2101, and they were administered asciminib at a twice-daily dose of 200 mg. Treatment was given until intolerable toxicity or treatment failure.

The median age of study participants was 54 years (range, 26-86), with 31% of patients aged 65 years and older and 9% aged 75 years and older. Eighty percent of patients were male, 47% were White, and 73% had an ECOG performance status of 0. Regarding prior therapies, 18%, 31%, 36%, 13%, and 2.2% of patients, respectively, received 1, 2, 3, 4, or 5 or more prior treatments.

Forty-two percent (95% CI, 28%-58%) of patients who received asciminib achieved MMR by 24 weeks; 49% of patients (95% CI, 34%-64%) achieved MMR by 96 weeks. The median duration of treatment was 108 weeks (range, 2-215).

References

1. Asciminib. Prescribing information. Novartis; 2021. Accessed October 29, 2021. https://bit.ly/3bllZws
2. FDA approves Novartis Scemblix (asciminib), with novel mechanism of action for the treatment of chronic myeloid leukemia. News release. Novartis. October 29, 2021. Accessed October 29, 2021. https://bit.ly/3bm9lNR