Brief Summary

This study is open to adults aged 18 years and older with different types of HER2+ cancer that has spread and cannot be removed by surgery. People can take part in this study if their tumours show HER2 aberrations and previous treatment was not successful. The purpose of this study is to find a suitable dose of zongertinib that people with different types of HER2+ cancer that has spread can tolerate best when taken together with trastuzumab deruxtecan (T-DXd), with trastuzumab emtansine (T-DM1), with trastuzumab and capecitabine, with zanidatamab, or with mFOLFOX6 (with or without trastuzumab). Another purpose is to check whether zongertinib alone and in combination with other treatments can make tumours shrink. Zongertinib inhibits HER2. HER2 causes cancer cells to grow.

In this study, participants receive treatment in cycles. Study participants are treated with zongertinib alone or in combination with other treatments. This study has 2 parts. In Part 1, participants in different groups receive increasing doses of zongertinib. In Part 2, participants are put into different groups by chance. Each group receives a different dose of zongertinib. Every participant has an equal chance of being in each group.

During the study, the participants visit the study site regularly. In this study, researchers want to find the highest dose of zongertinib that participants can tolerate when taken together with other treatments. To find this out, researchers look at certain severe health problems that a number of participants have. The doctors regularly check the size of the tumour with imaging methods (CT/MRI) during the study. The doctors also regularly check participants' health and take note of any unwanted effects.

Conditions

• Metastatic Breast Cancer
• Metastatic Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma
• Esophageal Adenocarcinoma
• Colorectal Cancer

Intervention / Treatment

• Drug: Zongertinib
• Drug: Trastuzumab deruxtecan
• Drug: Trastuzumab emtansine
• Drug: Trastuzumab
• Drug: Capecitabine
• Drug: mFOLFOX6
• Drug: zanidatamab

Primary Outcome Measures

• Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period (up to 21 days)
  The MTD evaluation period is defined as the first 21 days of the first treatment cycle for Cohorts A, B, C, G, K, and O. The MTD evaluation period is defined as the first 28 days after the first administration of any trial medication for Cohorts M and N.
• Dose optimization and justification (Phase II): Objective response (OR) (up to 50 months)
  Objective response (OR) is defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, or treatment discontinuation as assessed by investigator review.

Countries

Belgium, China, France, Germany, Italy, Japan, South Korea, Spain, United Kingdom, United States

Locations and Investigators

• The Oncology Institute of Hope and Innovation, Cerritos, United States (Recruiting)
  • Boehringer Ingelheim
• Ellison Medical Institute, Los Angeles, United States (Recruiting)
  • Boehringer Ingelheim
• Valkyrie Clinical Trials, Los Angeles, United States (Recruiting)
  • Boehringer Ingelheim
• University of California Los Angeles, Los Angeles, United States (Recruiting)
  • Boehringer Ingelheim
• University of California Irvine, Orange, United States (Recruiting)
  • Boehringer Ingelheim
• Sharp Memorial Hospital, San Diego, United States (Recruiting)
  • Boehringer Ingelheim
• Yale University School of Medicine, New Haven, United States (Recruiting)
  • Boehringer Ingelheim
• Helios CR Inc, Lakeland, United States (Recruiting)
  • Boehringer Ingelheim
• H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States (Recruiting)
  • Boehringer Ingelheim
• Orchard Healthcare Research Inc.- Skokie, Skokie, United States (Recruiting)
  • Boehringer Ingelheim
• Community Health Network, Indianapolis, United States (Recruiting)
  • Boehringer Ingelheim
• University of Iowa Hospitals and Clinics, Iowa City, United States (Recruiting)
  • Boehringer Ingelheim
• Dana-Farber Cancer Institute, Boston, United States (Recruiting)
  • Boehringer Ingelheim
• University of Michigan, Ann Arbor, United States (Not yet recruiting)
  • Boehringer Ingelheim
• Memorial Sloan-Kettering Cancer Center, New York, United States (Recruiting)
  • Boehringer Ingelheim
• New York Cancer & Blood Specialists, Shirley, United States (Recruiting)
  • Boehringer Ingelheim
• Penn State Milton S. Hershey Medical Center, Hershey, United States (Recruiting)
  • Boehringer Ingelheim
• Avera Cancer Institute, Sioux Falls, United States (Recruiting)
  • Boehringer Ingelheim
• Baptist Cancer Center - Memphis, Memphis, United States (Recruiting)
  • Boehringer Ingelheim
• SCRI Oncology Partners, Nashville, United States (Recruiting)
  • Boehringer Ingelheim
• Tennessee Oncology, Pllc, Nashville, United States (Recruiting)
  • Boehringer Ingelheim
• The Methodist Hospital Research Institute, Houston, United States (Recruiting)
  • Boehringer Ingelheim
• The University of Texas MD Anderson Cancer Center, Houston, United States (Recruiting)
  • Boehringer Ingelheim
• Inova Schar Cancer Institute, Fairfax, United States (Recruiting)
  • Boehringer Ingelheim
• Virginia Cancer Specialists, PC, Fairfax, United States (Recruiting)
  • Boehringer Ingelheim
• Fred Hutchinson Cancer Research Center, Seattle, United States (Recruiting)
  • Boehringer Ingelheim
• Cliniques Universitaires Saint-Luc, Brussels, Belgium (Recruiting)
  • Boehringer Ingelheim
• Universitair Ziekenhuis Antwerpen, Edegem, Belgium (Recruiting)
  • Boehringer Ingelheim
• UZ Leuven, Leuven, Belgium (Recruiting)
  • Boehringer Ingelheim
• Hôpital Vivalia De Libramont, Libramont-Chevigny, Belgium (Recruiting)
  • Boehringer Ingelheim
• Centre Hospitalier Universitaire de Liège, Liège, Belgium (Terminated)
• CHU UCL Namur, Namur, Belgium (Recruiting)
  • Boehringer Ingelheim
• Jilin Province Cancer Hospital, Changchun, China (Recruiting)
  • Boehringer Ingelheim
• The First Hospital of Jilin University, Changchun, China (Recruiting)
  • Boehringer Ingelheim
• Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China (Recruiting)
  • Boehringer Ingelheim
• Harbin Medical University Cancer Hospital, Harbin, China (Recruiting)
  • Boehringer Ingelheim
• Jiangsu Province Hospital, Nanjing, China (Recruiting)
  • Boehringer Ingelheim
• Fudan University Shanghai Cancer Center, Shanghai, China (Recruiting)
  • Boehringer Ingelheim
• Tianjin Cancer Hospital, Tianjin, China (Recruiting)
  • Boehringer Ingelheim
• Henan Cancer Hospital, Zhengzhou, China (Recruiting)
  • Boehringer Ingelheim
• INS Bergonie, Bordeaux, France (Recruiting)
  • Boehringer Ingelheim
• CTR François Baclesse, Caen, France (Recruiting)
  • Boehringer Ingelheim
• CTR Leon Berard, Lyon, France (Recruiting)
  • Boehringer Ingelheim
• INS Paoli-Calmettes, Marseille, France (Recruiting)
  • Boehringer Ingelheim
• HOP Tenon, Paris, France (Recruiting)
  • Boehringer Ingelheim
• CTR Eugène Marquis, Rennes, France (Not yet recruiting)
  • Boehringer Ingelheim
• Institut de Cancérologie de l'Ouest, Saint-Herblain, France (Recruiting)
  • Boehringer Ingelheim
• Institut de Cancérologie de Strasbourg, Strasbourg, France (Recruiting)
  • Boehringer Ingelheim
• INS Claudius Regaud IUCT-Oncopole, Toulouse, France (Recruiting)
  • Boehringer Ingelheim
• Institut Gustave Roussy, Villejuif, France (Recruiting)
  • Boehringer Ingelheim

And 54 other sites.