Oncothyreon Inc. and Array BioPharma Inc. have announced the initiation of a Phase 1b trial of ONT-380 (ARRY-380) in combination with Kadcyla® (ado-trastuzumab emtansine or TDM-1) in patients with metastatic HER2+ breast cancer.
ONT-380 is an orally active, reversible and selective small-molecule HER2 inhibitor invented by Array and being developed by Oncothyreon in collaboration with Array.
The trial (ClinicalTrials.gov Identifier NCT01983501) is a dose-escalation study in up to 48 patients who have been previously treated with Herceptin® (trastuzumab) and a taxane for metastatic breast cancer.
The primary objective is to determine the maximum-tolerated and/or recommended Phase 2 dose (MTD/RP2D) of ONT-380 in combination with the approved dose of Kadcyla.
Secondary objectives include an evaluation of the safety and preliminary anti-tumor activity of the combination. Following determination of the MTD/RP2D, the study includes an expansion arm at the MTD/RP2D as well as an optional second expansion arm in patients with central nervous system metastases.
"ONT-380 and Kadcyla are both directed at HER2, but with differing mechanisms of action," said Diana Hausman, M.D., Chief Medical Officer of Oncothyreon.
Hausman continued, "The strategy of combining two agents targeting HER2 has previously proven useful in HER2+ breast cancer, and we believe the combination of ONT-380 and Kadcyla is particularly relevant to evaluate as the treatment of metastatic HER2+ breast cancer continues to evolve."