ORLANDO ­– ABL001, an investigational potent, specific BCR-ABL1 inhibitor, exhibited rapid dose-dependent antitumor activity and seemed well tolerated in heavily pretreated patients with chronic myelogenous leukemia (CML), a study presented at the American Society of Hematology (ASH) 57th Annual Meeting has shown.1

For the multicenter, open-label, phase 1 study, researchers treated 59 patients with CML in chronic or accelerated phase who failed 2 or more prior tyrosine kinase inhibitors (TKIs) with ABL001 orally twice daily at a dose of 10 mg, 20 mg, 40 mg, 80 mg, or 150 mg. Only 1 patient had accelerated phase disease. Treatment with ABL001 continued until disease progression, unacceptable toxicity, withdrawal of consent, or death.

“We have had a remarkably low rate of discontinuation for a phase 1 trial,” Oliver Ottmann, MD, hematologist at Cardiff University in Cardiff, United Kingdon, said during his presentation.

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A maximum tolerated dose has not yet been reached. Results showed that ABL001 demonstrated activity at doses 10 mg or higher twice daily. Researchers found that all 12 patients in hematologic relapse achieved complete hematologic response within 2 months and 8 of the 12 TKI-resistant patients in cytogenetic relapse achieved a complete cytogenetic response within 3 to 6 months. Of the 29 patients in molecular relapse, 10 achieved a major molecular response within 6 months.

The study also demonstrated clinical activity across TKI-resistant mutations, such as V299L, F317L, and Y253H.

In regard to safety, there were 5 dose-limiting toxicities, including 2 grade 3 lipase elevation at 40 mg twice daily and 200 mg once daily, 1 grade 2 arthralgia at 80 mg twice daily, 1 acute coronary syndrome at 150 mg twice daily, and grade 3 bronchospasm at 200 mg twice daily. There were also 3 incidents of grade 2 acute pancreatitis during cycle 5 at doses 80 mg or higher twice daily.

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The most common grade 3 or 4 adverse events were anemia, thrombocytopenia, neutropenia, hypophosphatemia, and lipase elevation. Of note, no patients died during the study.

”Allosteric inhibition of BCR-ABL001 is a promising therapeutic approach in patients with CML,” Dr Ottmann concluded. “Enrollment to determine a recommended dose and to assess safety and tolerability is ongoing.”


  1. Ottmann O, Alimena G, DeAngelo DJ, et al. ABL001, a potent, allosteric Inhibitor of BCR-ABL, exhibits safety and promising single-agent activity in a phase I study of patients with CML with failure of prior TKI therapy. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.