Olverembatinib has demonstrated antitumor activity in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), new research suggests.
In a phase 1b trial, olverembatinib produced responses in patients with CML or Ph+ ALL who could not tolerate or had disease that was resistant to at least 2 BCR-ABL tyrosine kinase inhibitors (TKIs). This included patients with intolerance/resistance to ponatinib and patients with T315I mutations.
These findings were presented at the 2022 ASH Annual Meeting by Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center in Houston.
The phase 1b trial (Clinicaltrials.gov identifier: NCT04260022) included 13 patients with Ph+ ALL and 38 patients with CML in the chronic phase (CP), acute phase, or blast phase. All patients either could not tolerate or had disease that was resistant to at least 2 BCR-ABL TKIs.
Overall, the median age at baseline was 51 years, and 80.4% of patients were White. Cardiovascular comorbidities were present in 54.9% of patients, including 35.3% with hypertension. Most patients had received 2 or more prior lines of salvage therapy, 75% had disease that was resistant to ponatinib, and 37.3% had a T315I mutation.
The patients were randomly assigned to receive olverembatinib at 30 mg, 40 mg, or 50 mg every other day.
A total of 23 patients with CML-CP were evaluable for efficacy. In this group, the complete cytogenetic response (CCyR) rate was 77.8%, and the major molecular response (MMR) rate was 43.5%. The CCyR rate was 85.7% in the 30 mg dose group, 85.7% in the 40 mg group, and 50% in the 50 mg group. The MMR rate was 55.6%, 40%, and 25%, respectively.
Among CML-CP patients with a T315I mutation, the CCyR rate was 87.5%, and the MMR rate was 55.6%. Among those with unmutated T315I, the CCyR rate was 70%, and the MRR rate was 35.7%.
Among CML-CP patients with ponatinib-resistant disease, the CCyR rate was 77.8%, and the MMR rate was 50%. Among patients who could not tolerate ponatinib, the CCyR rate was 100%, and the MMR rate was 25%.
There were 7 evaluable patients with advanced Ph+ ALL. In this group, the CCyR rate was 28.6%, the MMR rate was 28.6%, and the major cytogenetic response (MCyR) rate was 42.9%.
Among Ph+ ALL patients in the 30 mg dosing group, 33.3% of patients each had a CCyR, MCyR, and MMR. There was 1 patient in the 40 mg dosing group, and that patient had a MCyR. In the 50 mg dosing group, 33.3% of patients each had a CCyR, MCyR, and MMR.
A total of 37 patients were evaluable for safety. The most common grade 3-4 adverse events (AEs) were thrombocytopenia (18.9%), neutropenia (16.2%), leukopenia (13.5%), and an increase in blood creatine phosphokinase levels (13.5%). Treatment discontinuation due to AEs occurred in 5.4% of patients.
Six patients had serious AEs. There were 2 cases of blood creatine phosphokinase elevation, 1 case of neutropenia, 1 case of obstructive pancreatitis, 1 patient with both sinus tachycardia and atrial fibrillation, and 1 patient with both generalized edema and troponin 1 elevation.
Dr Jabbour concluded that olverembatinib was safe and well tolerated up to the 50 mg dose, and the drug proved effective in both refractory CML-CP and advanced Ph+ ALL.
Disclosures: This research was supported by Ascentage Pharma Group Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Jabbour E, Koller PB, Oehler VG, et al. Olverembatinib (HQP1351) overcomes ponatinib resistance in patients with heavily pretreated/refractory chronic myeloidleukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Presented at ASH 2022. December 10-13, 2022. Abstract 82.