Tucatinib (ONT-380)

Target: HER2 | Disease State: Breast Cancer

Introduction / Brief Description

Tucatinib is an orally active, reversible and selective small-molecule HER2 inhibitor invented by Array and licensed to Cascadian Therapeutics (previously named Oncothyreon) for development, manufacturing and commercialization. The December 2014 License Agreement replaces the prior Development and Collaboration Agreement under which Cascadian and Array were jointly developing ONT-380. As part of the License Agreement, Cascadian paid Array $20 million as an up-front fee. In March 2018, Seattle Genetics acquired Cascadian Therapeutics. The licensing agreement between Array and Cascadian remains in effect and Array will be entitled to double-digit royalty payments from net sales of Tucatinib going forward.

Tucatinib is highly active as a single agent and in combination with both chemotherapy and Herceptin® (trastuzumab) in xenograft models of HER2+ breast cancer, including models of CNS metastases that were refractory to Tykerb® (lapatinib) or neratinib treatment. Tucatinib is advancing in one Phase 2/registration and three Phase 1b combination trials in patients with metastatic breast cancer.

Breast Cancer

Breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed. While significant progress has been made in the treatment of breast cancer, globally around 520 thousand women die from the disease annually. In 2014, it is projected that over 230 thousand women will be diagnosed with breast cancer and approximately 40 thousand will die from the disease in the United States. Approximately 20% of patients with breast cancer test positive for HER2, which promotes the growth of cancer cells. Brain metastasis is observed in 10% of metastatic breast cancer patients, with an even higher likelihood in HER2+ disease (15%-29%). Many of the breast cancer therapies (like targeted antibodies) fail to penetrate the blood–brain barrier, hence allowing for tumor recurrence in the central nervous system. Therefore, an effective therapy for patients with HER2+ patients with brain metastases would address a significant unmet need in the treatment of breast cancer.

Clinical Trials

Trial Data
Trial Title
Program: ARRY-380 (ONT-380)
Phase: 1b
Status: Active, not recruiting
Disease: Brain metastases from HER2+ breast cancer
Sponsor: Dana-Farber Cancer Institute
Trial Information: NCT01921335
Trial Title: Phase I Dose-escalation Trial of ARRY-380 in Combination With Trastuzumab in Participants With Brain Metastases From HER2+ Breast Cancer
Program: ARRY-380 (ONT-380)
Phase: 1b
Status: Active, not recruiting
Disease: HER2+ breast cancers
Sponsor: Oncothyreon
Trial Information: NCT02025192
Trial Title: A Phase 1b Study of ONT-380 Combined With Capecitabine and/or Trastuzumab in Patients With HER2+ Metastatic Breast Cancer
Program: ARRY-380 (ONT-380)
Phase: 1b
Status: Active, not recruiting
Disease: HER2+ breast cancers
Sponsor: Oncothyreon
Trial Information: NCT01983501
Trial Title: A Phase 1b Study of ONT-380 Combined With Ado-trastuzumab Emtansine (T-DM1) in Patients With HER2+ Breast Cancer

To learn more about tucatinib clinical trials, click here.

Publications and Presentations

ARRY-380

06/01/2015

American Society of Clinical Oncology Meeting

ONT-380 in the Treatment of HER2+ Breast Cancer Central Nervous System (CNS) Metastases (Mets)

C. Ferrario, et al.

ARRY-380

10/17/2012

American Association of Pharmaceutical Scientists, Annual Meeting and Exposition

Amorphous Dispersion Development of ARRY-380, an ErbB2 Selective Inhibitor

C. Lindemann, et al.

ARRY-380

10/17/2012

American Association of Pharmaceutical Scientists, Annual Meeting and Exposition

Solid-State Characterization of Seven Isomorphic Solvates of ARRY-380

C. Lindemann, et al.


To view all publications, click here.

These compounds and their uses are investigational and have not been approved by the U.S. Food and Drug Administration. This information is presented only for purposes of providing a general overview of our clinical trials only.