HERTHENA-Breast-01: A Phase 1b/2, Multicenter, Open-label, Dose- Finding Study to Evaluate the Safety and Antitumor Activity of Patritumab Deruxtecan in Participants with HER2 Positive Unresectable Locally Advanced Breast Cancer or Metastatic Breast Cancer

Researchers are looking for new ways to treat people with human epidermal growth factor receptor 2 (HER2) positive breast cancer. While HER2-targeted treatments have significantly enhanced outcomes for patients with HER2 positive breast cancer, there is an important unmet medical need for safe and effective treatment options.About 81 participants, aged at least 18 years old, will be in this trial and have HER2 positive breast cancer that cannot be removed by surgery or has spread to other parts of the body.This trial is testing patritumab deruxtecan given in combination with other anti-cancer drugs that are standard treatment for people with advanced HER2 positive breast cancer. The other anti-cancer drugs that will be used in this trial are trastuzumab, pertuzumab and tucatinib.Patritumab deruxtecan is experimental. It has not been approved to be given alone or in combination with other anti-cancer drugs to treat any type of cancer.Participants will be placed in 1 of 3 groups:• Group 1: Patritumab deruxtecan + trastuzumab• Group 2: Patritumab deruxtecan + trastuzumab + pertuzumab• Group 3: Patritumab deruxtecan + trastuzumab + tucatinibEach group will test different dose levels of patritumab deruxtecan.Patritumab deruxtecan, trastuzumab, and pertuzumab are given by a needle in a vein (intravenous infusion) every 3 weeks.Tucatinib is a tablet taken by mouth two times daily.During the trial, participant will give urine, blood, and tumour samples, have imaging tests and physical examinations.Participants may be in the trial for approximately 3 years.