Olverembatinib shows therapeutic potential in chronic-phase CML

The novel, small-molecule, orally administered third-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) olverembatinib is well-tolerated and shows promising antitumour activity in patients with heavily pretreated chronic-phase chronic myeloid leukaemia (CML), according to the results of a phase 1B study.

The multicentre study included 80 patients (median age 54.0 years, 58 percent male) with CML or Philadelphia chromosome–positive acute lymphoblastic leukaemia resistant or intolerant to at least two TKIs. These patients were randomly assigned to receive 30, 40, or 50 mg of olverembatinib orally every other day in 28-day cycles.

Olverembatinib was generally well tolerated, with patients receiving treated for a median duration of 48 weeks. Treatment-related adverse events (AEs) were documented in 60 patients (75 percent), including grade 3 or higher treatment-related AEs in 32 (40 percent) and treatment-related serious AEs in 12 (15 percent). None of these AEs were fatal.

The most common (at least 10 percent) treatment-emergent AEs were elevated blood creatine phosphokinase (all grades 39 percent, grade 3 or higher 13 percent) and thrombocytopenia (all grades 29 percent, grade 3 or higher 18 percent).

Among evaluable patients with chronic-phase CML, complete cytogenetic response (CCyR) was achieved by 31 of 51 patients (61 percent), while major molecular response (MMR) occurred in 25 of 59 patients (42 percent). Cytogenetic and molecular responses did not differ between patients with and without T315I variants.

Among patients with prior ponatinib treatment, CCyR occurred in 15 of 26 (58 percent) and MMR occurred in 11 of 30 (37 percent). Among patients with asciminib resistance, four of eight achieved CCyR (50 percent) had CCyR and four of 12 achieved MMR (33 percent).

The recommended phase III dose of olverembatinib is 30 mg every other day in patients without T315I variants.

The findings suggest that olverembatinib may be a viable new treatment option for patients with chronic-phase CML after failure of two or more TKIs.