Novartis investigational STAMP inhibitor asciminib shows superior major molecular response rate to Bosulif in chronic myeloid leukemia trial.

Detailed results from the Phase III ASCEMBL study demonstrate that, at 24 weeks, asciminib (ABL001) – a novel investigational treatment specifically targeting the ABL myristoyl pocket (STAMP) – nearly doubled the major molecular response (MMR) rate compared to Bosulif (bosutinib) (25.5% vs. 13.2%, respectively ([95% CI, 2.19-22.3]; 2-sided P=0.029) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine-kinase inhibitors (TKIs) These data were presented at a late-breaking abstracts session during the 62nd American Society of Hematology Annual Meeting & Exposition (ASH). Despite the significant advances in the CML treatment landscape, many patients treated with two or more TKIs experience intolerance; for example, in an analysis of studies in patients who had previously failed two TKIs, up to 55% reported intolerance to treatment. In addition, resistance rates for patients in later treatment lines remain high; and in the second-line setting, at least three out of five patients are unable to achieve MMR and up to 56% of patients do not achieve complete cytogenetic response (CCyR) within two years of follow-up. With few remaining treatment options, and no currently established standard-of-care in the third-line setting per treatment guidelines, patients who are resistant or intolerant to two or more TKIs are at a high risk of progression. In the ASCEMBL trial , 233 patients were randomized to receive asciminib 40 mg twice daily (n=157) or Bosulif 500 mg once a day (n=76). Data showed that, at 24 weeks, more patients achieved a CCyR in the asciminib arm (40.8%) than in the Bosulif arm (24.2%); and deep molecular response (DMR) rates were higher for patients in the asciminib arm than in the Bosulif arm – with 10.8% and 8.9% patients achieving MR4 and MR4.5 on asciminib, respectively, vs. 5.3% and 1.3% on Bosulif. Grade greater than 3 adverse events (AEs) occurred in 50.6% and 60.5% of patients treated with asciminib and Bosulif, respectively. Treatment discontinuation due to AEs in the asciminib arm was 5.8% compared to 21.1% for patients taking Bosulif . Similarly, AEs requiring dose interruption and/or dose adjustments were reported less frequently with asciminib than with Bosulif (37.8% vs. 60.5%, respectively). At data cutoff, more patients were still on treatment in the asciminib arm vs. the Bosulif arm (61.8% vs. 30.3%, respectively). The most common grade, greater than 3 AEs (occurring in greater than 10%), of patients treated with asciminib were thrombocytopenia (17.3%) and neutropenia (14.7%), while for Bosulif they were increased alanine aminotransferase (ALT) (14.5%), neutropenia (11.8%) and diarrhea (10.5%). On-treatment deaths on the asciminib arm occurred in two (1.3%) patients (ischemic stroke and arterial embolism); there was one (1.3%) death on Bosulif (septic shock). The most frequent AEs (all grades; greater than 20%) were thrombocytopenia (28.8%) and neutropenia (21.8%) in the asciminib arm, compared to diarrhea (71.1%), nausea (46.1%), increased ALT (27.6%), vomiting (26.3%), rash (23.7%), increased aspartate aminotransferase (21.1%), neutropenia (21.1%) and thrombocytopenia (18.4%) in the Bosulif arm. The FDA has granted Fast Track designation for asciminib. Submission to the US and EU health authorities is planned for the first half of 2021. .