Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread

Phase 1

Recruiting

• Conditions: Metastatic Breast Cancer; Metastatic Gastric Adenocarcinoma; Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Interventions: Drug: Zongertinib; Drug: Trastuzumab emtansine; Drug: Trastuzumab deruxtecan; Drug: Trastuzumab; Drug: Capecitabine

• Registration Number: NCT06324357
• Lead Sponsor: Boehringer Ingelheim

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), or with trastuzumab and capecitabine. 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-15
• Study First Submitted QC: 2024-03-15
• Study First Posted: 2024-03-21
• Study Start: 2024-06-28
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-29
• Last Update Posted: 2025-09-02
• Primary Completion: 2029-09-28
• Study Completion: 2029-09-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 582

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 after HER2-directed treatment (including treatment with trastuzumab deruxtecan (T-DXd) for non-T-DXd combination cohorts) for unresectable locally advanced or metastatic disease.
• 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, personal or family history of long QT syndrome or unexplained sudden death under 40 years-of-age.

• Ejection fraction <50% or the lower limit of normal of the institutional standard within 28 days prior to randomization.

• Women who are pregnant or 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, T-DM1, trastuzumab or capecitabine and trastuzumab.

Further exclusion criteria apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase Ib - Cohort A: zongertinib + Trastuzumab emtansine	Zongertinib	Dose escalation (Phase Ib)
Phase Ib - Cohort A: zongertinib + Trastuzumab emtansine	Trastuzumab emtansine	Dose escalation (Phase Ib)
Phase Ib - Cohort B: zongertinib + Trastuzumab deruxtecan	Zongertinib	Dose escalation (Phase Ib)
Phase Ib - Cohort B: zongertinib + Trastuzumab deruxtecan	Trastuzumab deruxtecan	Dose escalation (Phase Ib)
Phase Ib - Cohort C: zongertinib + Trastuzumab deruxtecan	Zongertinib	Dose escalation (Phase Ib)
Phase Ib - Cohort C: zongertinib + Trastuzumab deruxtecan	Trastuzumab deruxtecan	Dose escalation (Phase Ib)
Phase II - Cohort D: zongertinib + Trastuzumab emtansine	Zongertinib	Dose optimization (Phase II).
Phase II - Cohort D: zongertinib + Trastuzumab emtansine	Trastuzumab emtansine	Dose optimization (Phase II).
Phase II - Cohort E: zongertinib + Trastuzumab deruxtecan	Zongertinib	Dose optimization (Phase II).
Phase II - Cohort E: zongertinib + Trastuzumab deruxtecan	Trastuzumab deruxtecan	Dose optimization (Phase II).
Phase II - Cohort F: zongertinib + Trastuzumab deruxtecan	Zongertinib	Dose optimization (Phase II).
Phase II - Cohort F: zongertinib + Trastuzumab deruxtecan	Trastuzumab deruxtecan	Dose optimization (Phase II).
Phase Ib - Cohort G: zongertinib + trastuzumab + capecitabine	Zongertinib	Dose escalation (Phase Ib)
Phase Ib - Cohort G: zongertinib + trastuzumab + capecitabine	Trastuzumab	Dose escalation (Phase Ib)
Phase Ib - Cohort G: zongertinib + trastuzumab + capecitabine	Capecitabine	Dose escalation (Phase Ib)
Phase Ib - Cohort K: zongertinib + trastuzumab	Zongertinib	Dose escalation (Phase Ib)
Phase Ib - Cohort K: zongertinib + trastuzumab	Trastuzumab	Dose escalation (Phase Ib)
Phase II - Cohort H: zongertinib + trastuzumab + capecitabine	Zongertinib	Dose optimization (Phase II).
Phase II - Cohort H: zongertinib + trastuzumab + capecitabine	Trastuzumab	Dose optimization (Phase II).
Phase II - Cohort H: zongertinib + trastuzumab + capecitabine	Capecitabine	Dose optimization (Phase II).
Phase II - Cohort I: zongertinib	Zongertinib	Dose optimization (Phase II).
Phase II - Cohort J: zongertinib + trastuzumab	Zongertinib	Dose optimization (Phase II).
Phase II - Cohort J: zongertinib + trastuzumab	Trastuzumab	Dose optimization (Phase II).
Phase II - Cohort I-ext: zongertinib	Zongertinib	Extension Phase II
Phase II - Cohort J-ext: zongertinib + trastuzumab	Zongertinib	Extension Phase II
Phase II - Cohort J-ext: zongertinib + trastuzumab	Trastuzumab	Extension Phase II

Primary Outcome Measures

Name	Time	Method
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.
Dose optimization (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.

Secondary Outcome Measures

Name	Time	Method
Dose escalation (Phase Ib): Objective response (OR)	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): Occurrence of dose-limiting toxicities (DLTs) during the entire treatment period	up to 50 months
Dose optimization (Phase II): Disease control (DC)	up to 50 months	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.
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) - EORTC IL19	up to 48 weeks	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".
Dose optimization (Phase II): Patient-reported outcome (PRO) - EORTC IL46	up to 48 weeks	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".
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)	up to 50 months	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.
Dose optimization (Phase II): Patient-reported outcome (PRO) - PRO-CTCAE	up to 24 weeks	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).

Trial Locations

Locations (100)

Mayo Clinic-Arizona; 🇺🇸 Phoenix, Arizona, United States

The Oncology Institute of Hope and Innovation; 🇺🇸 Cerritos, California, United States

Ellison Medical Institute; 🇺🇸 Los Angeles, California, United States

Valkyrie Clinical Trials; 🇺🇸 Los Angeles, California, United States

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

University of California Irvine; 🇺🇸 Orange, California, United States

Sharp Memorial Hospital; 🇺🇸 San Diego, California, United States

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Mayo Clinic - Florida; 🇺🇸 Jacksonville, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States

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