Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib in Combination With Trastuzumab Deruxtecan or With Trastuzumab Emtansine and to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread

Beamion BCGC-1: A Phase Ib Dose Escalation and Phase II Dose Optimization, Randomized, Open-label, Multicenter Trial of Oral Zongertinib (BI 1810631) in Combination With Intravenous Trastuzumab Deruxtecan (T-DXd) or in Combination With Intravenous Trastuzumab Emtansine (T-DM1) for Treatment of Patients With Advanced HER2+ Metastatic Breast Cancer (mBC) and Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (mGEAC)

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) or with trastuzumab emtansine (T-DM1). Another purpose is to check whether zongertinib in combination with T-DXd or with T-DM1 can make tumours shrink. Zongertinib inhibits HER2. HER2 causes cancer cells to grow.

The study is split into treatment cycles. All study participants are treated with zongertinib in combination with T-DXd or with T-DM1. This study has 2 parts. In Part 1, participants 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 T-DXd or with T-DM1. 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Breast Cancer; Esophageal Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Zongertinib; Drug: Trastuzumab emtansine; Drug: Trastuzumab deruxtecan

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Boehringer Ingelheim; Phone Number: 1-800-243-0127; Email: clintriage.rdg@boehringer-ingelheim.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed and dated written Informed consent form (ICF) in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
• Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the ICF.
• Documented Human epidermal growth factor receptor 2 overexpressing and/or amplified (HER2+), metastatic breast cancer (mBC) or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma (mGEAC).
• For dose optimization (Phase II): Patient must provide tumor tissue from locations not radiated prior to biopsy, if possible, collected through archival tissue.
• Documented investigator assessed progression.
• Recovered from any previous therapy-related toxicity to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at start of treatment (except for alopecia, stable sensory neuropathy, and hypothyroidism (patients on thyroid replacement therapy) which must be ≤ CTCAE Grade 2).
• Presence of at least one measurable lesion according to Response evaluation criteria in solid tumors (RECIST) 1.1, as determined by the local site investigator/radiology assessment.
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. Further inclusion criteria apply.

Exclusion Criteria:

• Previous or concomitant malignancies other than the one treated in this trial within the previous 2 years, which require current systemic therapy except:

  • effectively treated non-melanoma skin cancers
  • effectively treated carcinoma in situ of the cervix
  • effectively treated ductal carcinoma in situ
  • other effectively treated malignancy that is considered cured by local treatment
• History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of ≥ III or IV, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the investigator. Myocardial infarction (or troponin levels consistent with myocardial infarction within 28 days of randomization), stroke, or pulmonary embolism within 6 months prior to randomization.
• Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting electrocardiograms, e.g. complete left bundle branch block, third degree heart block.
• Mean resting corrected QT interval (QT interval corrected for heart rate by Fridericia´s formula (QTcF)) >470 msec.
• Any factors that increase the risk of QT interval corrected for heart rate (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age. Or any concomitant medication known to prolong the QT interval.
• Ejection fraction <50% or the lower limit of normal of the institutional standard within 28 days prior to randomization.
• Women who are pregnant, nursing, or who plan to become pregnant or nurse during the trial or within 7 months after the last dose of trial treatment with T-DXd or T-DM1.

Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase Ib - Cohort A: zongertinib + Trastuzumab emtansine; Dose escalation (Phase Ib)	Drug: Zongertinib; Zongertinib; Other Names: BI 1810631; Drug: Trastuzumab emtansine; Trastuzumab emtansine; Other Names: T-DM1; Kadcyla®
Experimental: Phase Ib - Cohort B: zongertinib + Trastuzumab deruxtecan; Dose escalation (Phase Ib)	Drug: Zongertinib; Zongertinib; Other Names: BI 1810631; Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan; Other Names: T-DXd; Enhertu®
Experimental: Phase Ib - Cohort C: zongertinib + Trastuzumab deruxtecan; Dose escalation (Phase Ib)	Drug: Zongertinib; Zongertinib; Other Names: BI 1810631; Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan; Other Names: T-DXd; Enhertu®
Experimental: Phase II - Cohort D: zongertinib + Trastuzumab emtansine; Dose optimization (Phase II).	Drug: Zongertinib; Zongertinib; Other Names: BI 1810631; Drug: Trastuzumab emtansine; Trastuzumab emtansine; Other Names: T-DM1; Kadcyla®
Experimental: Phase II - Cohort E: zongertinib + Trastuzumab deruxtecan; Dose optimization (Phase II).	Drug: Zongertinib; Zongertinib; Other Names: BI 1810631; Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan; Other Names: T-DXd; Enhertu®
Experimental: Phase II - Cohort F: zongertinib + Trastuzumab deruxtecan; Dose optimization (Phase II).	Drug: Zongertinib; Zongertinib; Other Names: BI 1810631; Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan; Other Names: T-DXd; Enhertu®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period	The MTD evaluation period is defined as the first 21 days of the first treatment cycle.	up to 21 days
Dose optimization (Phase II): Objective response (OR)	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.	up to 50 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose escalation (Phase Ib): Objective response (OR)		up to 50 months
Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) during the entire treatment period		up to 50 months
Dose escalation (Phase Ib): Maximum measured concentration of the analyte in plasma (Cmax)		up to 50 months
Dose escalation (Phase Ib): Area under the concentration-time curve of the analyte in plasma from 0 to t2 (AUC0-t2)		up to 50 months
Dose optimization (Phase II): Progression-free survival (PFS)	PFS is defined as the time from treatment start until the earliest date of tumor progression according RECIST 1.1 based on investigator review or death from any cause, whichever occurs first.	up to 50 months
Dose optimization (Phase II): Disease control (DC)	DC is defined as best overall response of complete response (CR) or partial response (PR) or stable disease (SD) where best overall response is defined according to RECIST 1.1 from first treatment administration until the earliest of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, or treatment discontinuation, as assessed by investigator review.	up to 50 months
Dose optimization (Phase II): Occurrence of treatment-emergent AEs leading to zongertinib (BI 1810631) dose reduction during the on-treatment period		up to 50 months
Dose optimization (Phase II): Maximum measured concentration of the analyte in plasma (Cmax)		up to 50 months
Dose escalation (Phase II): Area under the concentration-time curve of the analyte in plasma from 0 to t2 (AUC0-t2)		up to 50 months
Dose optimization (Phase II): Patient-reported outcome (PRO) - PRO-CTCAE	The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) item library was developed to elicit symptomatic toxicity information directly from patients in cancer clinical trials. The items selected for this trial are: Mouth/throat sores, Taste changes, Decreased appetite, Nausea, Vomiting, Constipation, Diarrhoea, Shortness of breath, Cough, Rash, Skin dryness, Hair loss, Itching, Numbness & Tingling, Fatigue, Nosebleed, Headache. PRO-CTCAE responses are scored from 0 (=none) to 4 (=very severe) (or 0/1 for absent/present).	up to 24 weeks
Dose optimization (Phase II): Patient-reported outcome (PRO) - EORTC IL46	The EORTC IL46 is a single question that assesses bother (burden) of treatment. It is rated on a scale from 1 to 4, ranging from "not at all" to "very much".	up to 48 weeks
Dose optimization (Phase II): Patient-reported outcome (PRO) - EORTC IL19	The EORTC IL19 consists of five physical functioning scale items. It is rated on a scale from 1 to 4, ranging from "not at all" to "very much".	up to 48 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): May 23, 2024
• Primary Completion (Estimated): February 22, 2027
• Study Completion (Estimated): August 21, 2028

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Breast Diseases; Head and Neck Neoplasms; Esophageal Diseases; Breast Neoplasms; Adenocarcinoma; Esophageal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immunoconjugates; Immunotoxins; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine; Trastuzumab deruxtecan
• Other Study ID Numbers: 1479-0012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

• IPD Sharing Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No