Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib in Combination With Trastuzumab Deruxtecan or With Trastuzumab Emtansine and to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread

• ClinicalTrials.gov Identifier: NCT06324357
• Recruitment Status: Not yet recruiting
• First Posted: March 21, 2024
• Last Update Posted: April 24, 2024
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: March 15, 2024
• First Posted Date: March 21, 2024
• Last Update Posted Date: April 24, 2024
• Estimated Study Start Date: May 15, 2024
• Estimated Primary Completion Date: February 22, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2024)

• 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.
• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 15, 2024)

• Dose escalation (Phase Ib): Objective response (OR) [ Time Frame: up to 50 months ]
• Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) during the entire treatment period [ Time Frame: up to 50 months ]
• Dose escalation (Phase Ib): Maximum measured concentration of the analyte in plasma (Cmax) [ Time Frame: up to 50 months ]
• Dose escalation (Phase Ib): Area under the concentration-time curve of the analyte in plasma from 0 to t2 (AUC0-t2) [ Time Frame: up to 50 months ]
• Dose optimization (Phase II): Progression-free survival (PFS) [ Time Frame: 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): Disease control (DC) [ Time Frame: 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 [ Time Frame: up to 50 months ]
• Dose optimization (Phase II): Maximum measured concentration of the analyte in plasma (Cmax) [ Time Frame: 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) [ Time Frame: up to 50 months ]
• Dose optimization (Phase II): Patient-reported outcome (PRO) - PRO-CTCAE [ Time Frame: 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).
• Dose optimization (Phase II): Patient-reported outcome (PRO) - EORTC IL46 [ Time Frame: 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 optimization (Phase II): Patient-reported outcome (PRO) - EORTC IL19 [ Time Frame: 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".

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib in Combination With Trastuzumab Deruxtecan or With Trastuzumab Emtansine and 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) in Combination With Intravenous Trastuzumab Deruxtecan (T-DXd) or in Combination With Intravenous Trastuzumab Emtansine (T-DM1) for Treatment of Patients With Advanced HER2+ Metastatic Breast Cancer (mBC) and Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (mGEAC)

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) or with trastuzumab emtansine (T-DM1). Another purpose is to check whether zongertinib in combination with T-DXd or with T-DM1 can make tumours shrink. Zongertinib inhibits HER2. HER2 causes cancer cells to grow.

The study is split into treatment cycles. All study participants are treated with zongertinib in combination with T-DXd or with T-DM1. This study has 2 parts. In Part 1, participants 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 T-DXd or with T-DM1. 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Metastatic Breast Cancer
• Metastatic Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma
• Esophageal Adenocarcinoma

Intervention

• Drug: Zongertinib
  Zongertinib
  Other Name: BI 1810631
• Drug: Trastuzumab deruxtecan
  Trastuzumab deruxtecan
  Other Name: T-DXd; Enhertu®
• Drug: Trastuzumab emtansine
  Trastuzumab emtansine
  Other Name: T-DM1; Kadcyla®

Study Arms

• Experimental: Phase Ib - Cohort A: zongertinib + Trastuzumab emtansine
  Dose escalation (Phase Ib)
  Interventions:

  • Drug: Zongertinib
  • Drug: Trastuzumab emtansine
• Experimental: Phase Ib - Cohort B: zongertinib + Trastuzumab deruxtecan
  Dose escalation (Phase Ib)
  Interventions:

  • Drug: Zongertinib
  • Drug: Trastuzumab deruxtecan
• Experimental: Phase Ib - Cohort C: zongertinib + Trastuzumab deruxtecan
  Dose escalation (Phase Ib)
  Interventions:

  • Drug: Zongertinib
  • Drug: Trastuzumab deruxtecan
• Experimental: Phase II - Cohort D: zongertinib + Trastuzumab emtansine
  Dose optimization (Phase II).
  Interventions:

  • Drug: Zongertinib
  • Drug: Trastuzumab emtansine
• Experimental: Phase II - Cohort E: zongertinib + Trastuzumab deruxtecan
  Dose optimization (Phase II).
  Interventions:

  • Drug: Zongertinib
  • Drug: Trastuzumab deruxtecan
• Experimental: Phase II - Cohort F: zongertinib + Trastuzumab deruxtecan
  Dose optimization (Phase II).
  Interventions:

  • Drug: Zongertinib
  • Drug: Trastuzumab deruxtecan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: March 15, 2024): 240
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 21, 2028
• Estimated Primary Completion Date: February 22, 2027 (Final data collection date for primary outcome measure)

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, 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.

Further exclusion criteria apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Boehringer Ingelheim; 1-800-243-0127; clintriage.rdg@boehringer-ingelheim.com

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT06324357
• Other Study ID Numbers: 1479-0012
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
• URL: https://www.mystudywindow.com/msw/datasharing

• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: April 2024