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

Trial details

Who runs it

Boehringer Ingelheim International GmbH

Trial code

EU 2023-509566-38-00

Record updated

2026. május 25.

Original description

Dose escalation (Phase Ib)Read full original descriptionShow less

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), metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC), or metastatic colorectal cancer (mCRC)

Dose escalation (Phase Ib)

• To characterize the safety, tolerability, and the dose-toxicity curve of zongertinib: o in combination with T-DM1 in patients with HER2+ mBC (Cohort A) o in combination with T-DXd in patients with HER2+ mBC (Cohort B) o in combination with T-DXd in patients with mGEAC (Cohort C) o in combination with capecitabine and trastuzumab in patients with HER2+ mBC (Cohort G) o in combination with trastuzumab in patients with HER2+ mBC (Cohort K) o in combination with mFOLFOX6 in patients with HER2+ mCRC (Cohort M) o in combination with trastuzumab and mFOLFOX6 in patients with HER2+ mCRC (Cohort N) o in combination with zanidatamab in patients with HER2+ mBC (Cohort O) by assessing escalating dose levels with overdose control to achieve primary objective of determining maximum tolerated doses (MTDs) and/or doses for further development per cohort

• To evaluate number of patients with "redacted as CCI" within MTD evaluation period per dose level. The MTD evaluation period is defined as the first 21 days of the first treatment cycle for Cohorts A, B, C, G, K, and O. The MTD evaluation period is defined as the first 28 days after the first administration of any trial medication for Cohorts M and N. The MTD is to be determined by dose escalation committee (DEC) based on the totality of data. It may be chosen as the highest dose with less than 25% risk of the true DLT rate being equal to or above 33% during MTD evaluation period based on the Bayesian Logistic Regression Model (BLRM) with overdose control (escalation with overdose control [EWOC]) for the trial

• The primary characterization of primary objective will be based on initial dose administered to patient during the MTD evaluation period and the strategy for handling intercurrent events will be a combined composite and principal stratum approach where some intercurrent events are considered as outcome and some define population consisting of patients who are able to adhere to the assigned treatment regimen and trial schedule

Dose optimization and justification (Phase II)

• To assess anti-tumor activity of zongertinib in the following settings to assist in selection of optimal dose for further clinical development: o in combination with T-DM1 in patients with HER2+ mBC (Cohort D) o in combination with T-DXd in patients with HER2+ mBC (Cohort E) o in combination with T-DXd in patients with HER2+ mGEAC (Cohort F) o in combination with capecitabine and trastuzumab in patients with HER2+ mBC (Cohort H) o as a monotherapy in patients with HER2+ mBC (Cohort I, I-ext) o in combination with trastuzumab in patients with HER2+ mBC (Cohort J, J-ext) o in combination with trastuzumab in patients with HER2+ mCRC (Cohort L, L-ext)

• The primary endpoint is proportion of patients with objective response (OR) by RECIST version 1.1 as assessed by investigator review in the intent-to-treat population

• The summary measure of OR will include all treated patients regardless of breaks from trial treatment but will exclude the effects of any subsequent anti-cancer therapy started before progression

Inclusion: 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 informed consent form (ICF); Cohorts A to K and Cohort O: Documented HER2+ mBC or mGEAC; Cohorts L (L-ext), M, and N (mCRC): Documented HER2 overexpression/amplification; For dose optimization and justification (Phase II): Patient must provide tumor tissue from locations not radiated prior to biopsy, if possible, collected through archival tissue; History of prior treatment lines in palliative setting: - For cohorts A, B, C, D, E, F, G, H, I, I-ext, J, J-ext, K and O documented investigator assessed progression; - For cohorts L, L-ext, M and N documented progression or recurrence of disease during or following their latest line of therapy; Presence of at least one measurable lesion according to RECIST 1.1; Eastern Cooperative Oncology Group (ECOG) score of 0 or 1; Adequate organ function based on laboratory values.

Exclusion: History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening; Mean resting corrected QT interval (QTcF) >470 msec; Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, 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.

EU CTIS 2023-509566-38-00