EU Approves Asciminib for Ph+ CML in Chronic Phase After 2 or More TKIs

The European Commission (EC) has approved asciminib (Scemblix) for the treatment of patients with Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase who received prior treatment with at least 2 TKIs.¹

The approval was based on data from the phase 3 ASCEMBL trial (NCT03106779), which showed that asciminib elicited a 24-week major molecular response (MMR) rate of 25.5%, compared with 13.2% for bosutinib (Bosulif; P = .029).² Additionally, long-term follow-up showed the 96-week MMR rate for asciminib was 37.6% (95% CI, 29.99%-45.65%) vs 15.8% (95% CI, 8.43%-25.96%) for bosutinib.³

“Until now, patients with CML in Europe had oral TKI therapies with the same mechanism of action to turn to, and those experiencing significant side effects or resistance to these treatment options would often cycle between these very similar therapies, with little success in controlling their disease or improving their quality of life,” Andreas Hochhaus, MD, head of the Department of Hematology and Medical Oncology at Jena University Hospital in Germany, stated in a press release. “The approval of [asciminib] in Europe is a timely milestone that will help many patients find hope for the management of their CML.”

Previously, in October 2021, the FDA granted an accelerated approval to asciminib for patients with Ph-positive CML in chronic phase who have previously been treated with 2 or more TKIs, based on findings from ASCEMBL and the phase 1 CABL001X2101 trial (NCT02081378). The latter study evaluated asciminib patients with Ph-positive CML in chronic phase harboring a T315I mutation.⁴

ASCEMBL evaluated asciminib, an oral STAMP inhibitor, vs bosutinib in patients with Ph-positive, chronic-phase CML who received prior treatment with a minimum of 2 ATP-binding site TKIs.⁵

Patients were required to be at least 18 years old with chronic-phase CML who met certain laboratory values at the time of screening and had a BCR-ABL1IS ratio of greater than 0.1%, per central laboratory at the screening examination for those intolerant to the most recent TKI treatment received. Additional inclusion criteria included disease progression or intolerance following the most recent TKI therapy.

Key exclusion criteria included a known T315I or V299L mutation at any time prior to study entry; a history of myocardial infarction, angina pectoris, coronary artery bypass graft within the 6 months before the initiation of study treatment; clinically significant cardiac arrythmias; or any other specific cardiac or cardiac repolarization abnormality.

Once enrolled, patients were randomly assigned 1:1 to 40 mg of asciminib twice daily or 500 mg of bosutinib once daily. The primary end point was 24-week MMR. Secondary end points included 96-week MMR, complete cytogenetic response (CCyR) rate, time to MMR, duration of MMR, time to CCyR, duration of CCyR, time to treatment failure, progression-free survival, overall survival, and safety.

Regarding safety, the most common any-grade adverse effects to occur in at least 20% of patients receiving asciminib were musculoskeletal pain (37.1%), upper respiratory tract infections (28.1%), thrombocytopenia (27.5%), fatigue (27.2%), headache (24.2%), arthralgia (21.6%), increased pancreatic enzymes (21.3%), abdominal pain (21.3%), diarrhea (20.5%) and nausea (20.2%).

“Approval of [asciminib] from the EC is a critical milestone to help bring this novel treatment to patients living with CML in Europe,” Haseeb Ahmad, president of Europe Innovative Medicines at Novartis, said in a news release. “Building on more than 20 years of innovation in CML, we are excited by the potential to once again transform the standard of care for more patients around the world.”

References

1. Novartis Scemblix^®, with novel mechanism of action, approved by the European Commission for adult patients with chronic myeloid leukemia. News release. Novartis. August 29, 2022. Accessed August 29, 2022. https://bit.ly/3AyRT4C
2. Rea D, Mauro MJ, Boquimpani C, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood. 2021 Nov 25;138(21):2031-2041. doi:10.1182/blood.2020009984
3. Rea D, Mauro MJ, Hochhaus A, et al. Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs): Week 96 update. J Clin Oncol. 2022;40(suppl 16):7004. doi:10.1200/JCO.2022.40.16_suppl.7004
4. FDA approves Novartis Scemblix (asciminib), with novel mechanism of action for the treatment of chronic myeloid leukemia. News release. Novartis. October 29, 2021. Accessed August 29, 2022. https://bit.ly/3bm9lNR
5. Study of efficacy of CML-CP patients treated with ABL001 versus bosutinib, previously treated with 2 or more TKIs. ClinicalTrials.gov. Updated July 14, 2022. Accessed August 29, 2022. https://clinicaltrials.gov/ct2/show/NCT03106779