STAMP inhibitor Asciminib (ABL001) for CML
by Dr. C.H. Weaver M.D. 2/2021
Data were presented at the December 2020 American Society of Hematology Annual Meeting (ASH) from the Phase III ASCEMBL clinical trial demonstrating that the novel precision cancer medicine asciminib (ABL001) nearly doubled the major molecular response (MMR) rate compared to Bosulif® (bosutinib) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). (1)
Tyrosine kinase inhibitors were one of the first precision cancer medicines developed and changed the management of CML. The advent and expansion of multiple TKI therapies has resulted in tremendous progress for patients living with CML over the last three decades. Some patients however in later treatment lines still can develop resistance leading to disease progression. There is currently no established standard-of-care in the third line setting of CML treatment.
About Asciminib (ABL001)
Asciminib (ABL001) is a precision cancer medicine targeting the ABL myristoyl pocket (STAMP) in patients with CML. Asciminib was designed to help overcome mutations on the ATP-binding site of BCR-ABL1, which may help address resistance that occurs in later treatment lines of CML and is being studied in several clinical trials in hopes of helping patients across multiple treatment lines of CML. (2)
The ASCEMBL clinical trial was designed to compare asciminib to Bosulif, and established and effective treatment for patients with Ph+ CML-CP previously treated with two or more tyrosine-kinase inhibitors TKI’s.
In the ASCEMBL clinical trial, 233 patients were treated with either asciminib 40 mg twice daily or Bosulif 500 mg once a day and directly compared. Patients were evaluated 24 weeks from initiation of therapy and 41% of asciminib treated patients achieved a cytogenetic complete remission compared to 24% of those treated with Bosulif. Treatment discontinuation due to side effects was less common with asciminib occurring in 5.8% compared to 21.1% for patients taking Bosulif.
The US Food and Drug Administration has granted Fast Track designation for asciminib and full submission to the US health authorities is planned for the first half of 2021. On Feb 8 Breakthrough Therapy designation was granted by the US Food and Drug Administration for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors and for the treatment of adult patients with Ph+ CML in CP harboring the T315I mutation.
- Hochhaus A, et al. Efficacy and Safety Results from ASCEMBL, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Previously Treated with ≥2 Tyrosine Kinase Inhibitors (TKIs). Oral presentation at: ASH Annual Meeting; Dec. 8, 2020.
- Schuld P., et al. Structural and Biochemical Studies Confirming the Mechanism of Action of Asciminib, an Agent Specifically Targeting the ABL Myristoyl Pocket (STAMP). Blood. 2020;136:34-35.