Ponatinib/Chemotherapy Improves MRD-Negative CRs Vs Imatinib in Ph+ ALL

Ponatinib (Iclusig) plus reduced-intensity chemotherapy met the primary end point of minimal residual disease-negative complete remission in the phase 3 PhALLCON trial (NCT03589326), demonstrating superiority compared with imatinib (Glivec) in patients with newly-diagnosed Philadelphia chromosome–positive (Ph-positive) acute lymphoblastic leukemia (ALL), according to a press release from Takeda.

Investigators of the PhALLCON trial reported no new safety signals. Data from the trial will be shared with the scientific community and discussed with regulatory agencies in the future.

“Ph-positive ALL is a fast-progressing disease with no targeted treatments currently approved in the frontline for patients in the U.S.,” Awny Farajallah, MD, head of Global Medical Affairs Oncology at Takeda, said in the press release. “There is an urgent need for an effective treatment that can suppress the development of difficult-to-treat mutations, which are associated with poor long-term outcomes. We are excited to see how [ponatinib] may be able to address this gap in care for these patients and look forward to sharing the results.”

The randomized, international, open-label phase 3 PhALLCON trial evaluated the efficacy and safety of ponatinib vs imatinib combined with reduced-intensity chemotherapy as a front-line therapy for adult patients with newly diagnosed Ph-positive ALL. In the first treatment arm, patients received an induction dose of oral ponatinib at 30 mg once daily with a 1.4 mg/m² intravenous dose of vincristine on days 1 and 14 of treatment, as well as 20 mg to 40 mg of dexamethasone taken orally on days 1 to 4 and days 11 to 14 for up to 3 cycles followed by induction ponatinib once daily. Following induction, patients received 1000 mg/m² and 250 mg/m² of cytarabine on days 1, 3, and 5 of cycles 2, 4, and 6 along with 1000 mg/m² and 250 mg/m² intravenous infusion of methotrexate on day 1 of cycles 1, 3, and 5. This treatment was followed by consolidation oral ponatinib once a day with 1.4 mg/m² intravenous infusion of vincristine on day 1 and 200 mg and 50 mg of prednisone on days 1 to 5 for up to 11 cycles in the maintenance phase. Patients in the comparator arm received 600 mg of oral imatinib once a day followed by the same chemotherapy backbone.

Secondary end points of the trial included event-free survival, molecular response, primary induction failure, overall response rate, and overall survival.

Patients who had newly diagnosed Ph-positive or breakpoint cluster region–Abelson-positive ALL and an ECOG performance status of less than 2 were eligible to enroll on the study. Patients were unsuitable for enrollment if they had a history or current diagnosis of chronic phase, accelerated phase, or blast phase chronic myeloid leukemia. Patients were also not able to enroll if they had prior or current treatment with any systemic anticancer therapy, were taking medication known to be strong inhibitors of cytochrome P450 within 14 days of the first dose of the study treatment, had major surgery 28 days prior to randomization, or a history of acute pancreatitis within 1 year of study screening.

Reference

Phase 3 Trial of ICLUSIG® (ponatinib) met primary endpoint in newly-diagnosed Ph+ ALL, a setting with no targeted treatments approved in the US. News release. Takada. November 17, 2022. Accessed November 17, 2022. http://bit.ly/3ArH99j