Clinical trial NCT06324357: 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
Official title: Beamion BCGC-1: A Phase Ib Dose Escalation and Phase II Dose Optimization, Randomized, Open-label, Multicenter Trial of Oral Zongertinib (BI 1810631) Alone or in Combination With Other Agents for the Treatment of Patients With Advanced HER2+ Metastatic Breast Cancer (mBC) and Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (mGEAC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Metastatic Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Esophageal Adenocarcinoma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2024-03-21
Enrollment: 582
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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, 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.

Primary outcomes:
measure: Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period
timeFrame: up to 21 days
measure: Dose optimization (Phase II): Objective response (OR)
timeFrame: up to 50 months
Secondary outcomes:
measure: Dose escalation (Phase Ib): Objective response (OR)
timeFrame: up to 50 months
measure: Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) during the entire treatment period
timeFrame: up to 50 months
measure: Dose escalation (Phase Ib): Maximum measured concentration of the analyte in plasma (Cmax)
timeFrame: up to 50 months
measure: Dose escalation (Phase Ib): Area under the concentration-time curve of the analyte in plasma from 0 to t2 (AUC0-t2)
timeFrame: up to 50 months
measure: Dose optimization (Phase II): Progression-free survival (PFS)
timeFrame: up to 50 months
measure: Dose optimization (Phase II): Disease control (DC)
timeFrame: up to 50 months
measure: Dose optimization (Phase II): Occurrence of treatment-emergent AEs leading to zongertinib (BI 1810631) dose reduction during the on-treatment period
timeFrame: up to 50 months
measure: Dose optimization (Phase II): Maximum measured concentration of the analyte in plasma (Cmax)
timeFrame: up to 50 months
measure: Dose escalation (Phase II): Area under the concentration-time curve of the analyte in plasma from 0 to t2 (AUC0-t2)
timeFrame: up to 50 months
measure: Dose optimization (Phase II): Patient-reported outcome (PRO) - PRO-CTCAE
timeFrame: up to 24 weeks
measure: Dose optimization (Phase II): Patient-reported outcome (PRO) - EORTC IL46
timeFrame: up to 48 weeks
measure: Dose optimization (Phase II): Patient-reported outcome (PRO) - EORTC IL19
timeFrame: up to 48 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Edegem
country: Belgium
facility: Edegem - UNIV UZ Antwerpen
city: Leuven
country: Belgium
facility: UZ Leuven
city: Libramont-Chevigny
country: Belgium
facility: UZ Antwerpen
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Namur
country: Belgium
facility: CHU UCL Namur - Site De Sainte-Elisabeth
city: Changchun
country: China
facility: Jilin Province Cancer Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Candiolo (TO)
country: Italy
facility: Istituto Di Candiolo
city: Foggia
country: Italy
facility: Az.Osp. Universitaria "Ospedali Riuniti"
city: Meldola (fc)
country: Italy
facility: Istituto Scientifico Romagnolo
city: Milano
country: Italy
facility: IRCCS San Raffaele
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale IRCCS Tumori Fondazione Pascale
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Aichi, Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Kagoshima-shi
country: Japan
facility: Hakuaikai Sagara Hospital
city: Kanagawa, Isehara
country: Japan
facility: Tokai University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Kanagawa Cancer Center
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
city: Kyoto, Kyoto
country: Japan
facility: Kyoto University Hospital
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo, Koto-ku
country: Japan
facility: Japanese Foundation for Cancer Research
city: A Coruña
country: Spain
facility: Hospital Teresa Herrera
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra - Madrid
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: CIO Clara Campal
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
Study officials:
References: