ONT-380 (ARRY-380)

Target: HER2 | Indication: Breast Cancer

Introduction / Brief Description

ONT-380 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 addition, Cascadian will pay Array a significant portion of any payments received from sublicensing ONT-380 rights. If Cascadian is acquired within three years of the effective date of the current agreement, Array will be eligible for up to $280 million in commercial and other milestone payments. Array is also entitled to receive up to a double-digit royalty based on net sales of ONT-380.

ONT-380 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. In a Phase 1 single agent clinical study, ONT-380 administered orally twice a day was well tolerated and demonstrated anti-tumor activity in heavily pre-treated HER2+ breast cancer patients with metastatic disease. Based on the strength of these preclinical and clinical trials, ONT-380 is advancing in one Phase 2 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

Publications

ARRY-380 / Breast Cancer

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 / Breast Cancer

10/07/2013

American Association for Cancer Research Special Conference on Advances in Breast Cancer Research

ONT-380 (ARRY-380) - an Oral HER2 Inhibitor - Final Phase 1 Results and Conclusions

V. F. Borges, et al.

ARRY-380 / Breast Cancer

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.