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
- Conditions
- Metastatic Breast CancerMetastatic Gastric AdenocarcinomaEsophageal AdenocarcinomaGastroesophageal Junction Adenocarcinoma
- Interventions
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 582
- 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.
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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
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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.
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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.
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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.
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Ejection fraction <50% or the lower limit of normal of the institutional standard within 28 days prior to randomization.
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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 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 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 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 (50)
Valkyrie Clinical Trials
🇺🇸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
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
The Methodist Hospital Research Institute
🇺🇸Houston, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Edegem - UNIV UZ Antwerpen
🇧🇪Edegem, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
UZ Antwerpen
🇧🇪Libramont-Chevigny, Belgium
Centre Hospitalier Universitaire de Liège
🇧🇪Liege, Belgium
CHU UCL Namur - Site De Sainte-Elisabeth
🇧🇪Namur, Belgium
Jilin Province Cancer Hospital
🇨🇳Changchun, China
The First Hospital of Jilin University
🇨🇳Changchun, China
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
🇨🇳Hangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Jiangsu Province Hospital
🇨🇳Nanjing, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
Istituto Di Candiolo
🇮🇹Candiolo (TO), Italy
Az.Osp. Universitaria "Ospedali Riuniti"
🇮🇹Foggia, Italy
Istituto Scientifico Romagnolo
🇮🇹Meldola (fc), Italy
IRCCS San Raffaele
🇮🇹Milano, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Istituto Nazionale IRCCS Tumori Fondazione Pascale
🇮🇹Napoli, Italy
Aichi Cancer Center Hospital
🇯🇵Aichi, Nagoya, Japan
Hakuaikai Sagara Hospital
🇯🇵Kagoshima-shi, Japan
Tokai University Hospital
🇯🇵Kanagawa, Isehara, Japan
Kanagawa Cancer Center
🇯🇵Kanagawa, Yokohama, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Japan
Kyoto University Hospital
🇯🇵Kyoto, Kyoto, Japan
Osaka International Cancer Institute
🇯🇵Osaka-shi, Japan
Japanese Foundation for Cancer Research
🇯🇵Tokyo, Koto-ku, Japan
Hospital Teresa Herrera
🇪🇸A Coruña, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Clínica Universidad de Navarra - Madrid
🇪🇸Madrid, Spain
Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital La Paz
🇪🇸Madrid, Spain
CIO Clara Campal
🇪🇸Madrid, Spain
Hospital Virgen Macarena
🇪🇸Sevilla, Spain