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Phase I Trial to Test New Anti-HER2 Pill

Study will assess safety and benefit of giving an experimental medicine with T-DM1 to treat metastatic, HER2-positive breast cancer

Trial Starts: October 2013 Trial Ends: August 2015

Written By Nicole Katze, MA, Editor and Manager, Content Development
Reviewed By Stefan Glück, MD, PhD

Researchers seek 48 women for a small, phase IB study of ONT-380, a new anti-HER2 medicine that can be taken by mouth. The pill will be given along with the standard amount of T-DM1, by vein.

About Phase I Clinical Trials

During phase I trials, a medicine is tested for the first time in humans, following several years of lab research and testing of the medicine in animals. The FDA must agree a treatment is reasonably safe before phase I trials can begin enrolling participants.  

Over the course of the study, the trial team closely  watches participants to find out how much of the medicine to give, in what way it is best given (by mouth, by vein, etc.), and whether it is safe to use. Safety is measured by watching for side effects that impact health or quality of life.

Sometimes, phase I trials combine a new medicine with one in standard use. This kind of trial is called a phase IB trial.


HER2-positive breast cancer grows when there are too many HER2 proteins present on breast cells. These extra proteins cause uncontrolled growth of the cells, or cancer. To treat the disease, doctors use anti-HER2 medicines that target the protein and stop it from helping cancer cells divide and spread. T-DM1 (Kadcyla) and trastuzumab (Herceptin) are two common examples of anti-HER2 therapies.

ONT-380 is a substance that also works to stop the HER2 protein from helping cancer grow. Past trials studied ONT-380 used alone to treat metastatic breast cancer, but doctors believe combining it with another anti-HER2 therapy may work better.

To find out, the trial team is assessing the combination of ONT-380 with T-DM1.


The researchers hope to find out

  • what dose of ONT-380 works best, and most safely, with T-DM1
  • how many tumors shrink or disappear with treatment, called tumor response
  • the combination’s impact on progression-free survival, the time from the start of treatment until the disease grows or spreads, or until death from any cause


  • Group 1 will take 300mgs of ONT-380 by mouth twice a day for a 21-day cycle, with T-DM1 given by vein every 21 days

If this group does not have disease growth and the combination is safe, then

  • group 2 will take 450mgs of ONT-380 by mouth twice a day for a 21 day cycle, with T-DM1 given by vein every 21 days

If this second group does not have disease growth and the combination is safe, then

  • group 3 will take 600mgs of ONT-380 by mouth twice a day for a 21 day cycle, with T-DM1 given by vein every 21 days

Participants will be followed up every 6 weeks for the first six cycles, and every 9 weeks starting with the seventh cycle.

Imaging scans will be taken every two cycles for the first six cycles, and then every three cycles after, to monitor how much the tumor grows or shrinks.


You may be eligible to take part in this trial if you

  • are a woman at least 18 years of age with metastatic, HER2-positive breast cancer
  • have been treated with a taxane-based chemotherapy and trastuzumab in the past
  • are not currently being treated with chemotherapy or radiation therapy
  • meet certain blood count requirements

You may not be eligible if you

  • have untreated brain metastases
  • have heart disease
  • have hepatitis B or C
  • are taking medicines that might interact with ONT-380

For more information or to find out if you are eligible, talk with your doctor about trial NCT01983501 on


This study is being held in Aurora, Colo., Nashville, Tenn., and Boston. For a full list of locations and contact information, visit