Early data demonstrate therapy leads to improved cytogenetic and molecular response rates in heavily pretreated and Ph+ patients.
Ariad Pharmaceuticals reported positive preliminary data from an ongoing Phase II trial with its investigational pan-BCR-ABL inhibitor, ponatinib, in 449 patients with chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) and those with Philadeophia-positive acute lymphoblastic leukemia (Ph+ ALL). Enrolled patients in the PACE study are either resistant or intolerant to therapy with dasatinib or nilotinib or have the T3151 mutation.
The reported results demonstrated that 47% of chronic-phase CML patients achieved a major cytogenetic response to ponatinib therapy, including 65% of patients with T3151 mutation. Thirty-nine percent of chronic-phase CML patients and 58% of T3151 mutation patients achieved a complete cytogenetic response. Moreover, 19% of chronic-phase patients overall achieved a major molecular response, including 33% of chronic-phase patients with the T3151 mutation.
These results are particularly encouraging, the firm points out, as most enrolled patients have only had one or two assessments for cytogenetic response because of the short follow-up. Prior clinical trials have also indicated that ponatinib response rates tend to increase over time.
“These preliminary results of the PACE trial show beneficial responses to ponatinib and a molecular response rate that already compared favorably to MMR rates seen with imatinib,” comments Frank G. Haluska, M.D., Ariad vp and CMO.
Ponatinib is separately in earlier clinical development for the treatment of acute myeloid leukemia and in preclinical development against solid tumors.