Beamion BCGC-1: A Phase Ib and Phase II trial of zongertinib in combination with intravenous trastuzumab deruxtecan (T-DXd) or in combination with intravenous trastuzumab emtansine (T-DM1) for treatment of patients with advanced HER2+ mBC and mGEAC

JRCT ID: jRCT2031240135

Registered date:03/06/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Advanced HER2+ mBC and mGEAC
• Date of first enrollment: 01/08/2024
• Target sample size: 240
• Countries of recruitment: Belgium,Japan,China,Japan,Italy,Japan,Spain,Japan,USA,Japan
• Study type: Interventional

Intervention(s)

Zongertinib (BI 1810631): Oral administration
Trastuzumab emtansine: intravenous administration
Trastuzumab deruxtecan: : intravenous administration

Outcome(s)

Primary Outcome

1. Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period [ Time Frame: up to 21 days ]
The MTD evaluation period is defined as the first 21 days of the first treatment cycle.

2. Dose optimization (Phase II): Objective response (OR) [ Time Frame: 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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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.

Related Information

• Primary Sponsor: Sila Aykut Yazgili