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)

Plain English Summary

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 is a Phase 2 clinical trial sponsored by Boehringer Ingelheim studying Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Colorectal Cancer. This trial is testing a new drug called Zongertinib, alone or with other cancer treatments, to see if it can shrink tumors in patients with advanced HER2-positive cancers. It is for adults with HER2-positive metastatic breast cancer, gastric, gastroesophageal junction, esophageal, or colorectal cancer that has spread and did not respond to previous treatments. Participation involves taking Zongertinib, possibly with other medications, and attending regular study site visits for monitoring and tests. Alternative treatments may include other chemotherapy, targeted therapies, or immunotherapy, depending on the specific cancer type and prior treatments. The trial aims to enroll 768 participants.

Official 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), with trastuzumab and capecitabine, with zanidatamab, or with mFOLFOX6 (with or without trastuzumab). 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 or older with specific types of HER2-positive cancers that have spread and are not treatable with surgery. Patients whose cancer has progressed after prior treatments, including those targeting HER2. Individuals with measurable lesions on scans and a good general health status (ECOG score of 0 or 1). People without active brain metastases, uncontrolled heart conditions, or certain lung conditions. This trial is studying Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Colorectal Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will determine the best dose of Zongertinib that is safe and effective, and how well it shrinks tumors, offering hope for better treatment responses. The specific primary outcome measures are: Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period (up to 21 days); Dose optimization and justification (Phase II): Objective response (OR) (up to 50 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a significant unmet need for patients with advanced HER2-positive cancers who have exhausted standard treatment options, by investigating a novel HER2 inhibitor. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Colorectal Cancer, where improved treatment options are needed.

Investor Insight

This trial signals a promising area of oncology research targeting HER2-driven cancers, with potential for a new therapeutic option in a market with significant patient populations. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval. The large enrollment target of 768 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the specific Zongertinib combination being tested for your cancer type and what to expect regarding treatment cycles and monitoring. Be prepared for regular visits to the study site for drug administration, blood tests, imaging scans to check tumor size, and health assessments. Understand that you may be assigned to different treatment groups by chance, and your health will be closely monitored for any side effects. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 768 participants

Interventions

• DRUG: Zongertinib — Zongertinib
• DRUG: Trastuzumab deruxtecan — Trastuzumab deruxtecan
• DRUG: Trastuzumab emtansine — Trastuzumab emtansine
• DRUG: Trastuzumab — Herceptin®
• DRUG: Capecitabine — Xeloda®

Primary Outcomes

• Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period (up to 21 days)
• Dose optimization and justification (Phase II): Objective response (OR) (up to 50 months)

Secondary Outcomes

• Dose escalation (Phase Ib): Objective response (OR) (up to 50 months)
• Dose escalation (Phase Ib): Occurrence of dose-limiting toxicities (DLTs) during the entire treatment period (up to 50 months)
• Dose escalation (Phase Ib): Maximum measured concentration of zongertinib (at steady state) (Cmax,(ss)) (up to 2 days)
• Dose escalation (Phase Ib): Area under the concentration-time curve of zongertinib over the time interval from 0 to 4h at steady state (AUC0-4h,ss) (up to 2 days)
• Dose escalation (Phase Ib): Area under the concentration-time curve of zongertinib over the time interval from 0 to the last quantifiable data point at steady state (AUC0-tz,ss) (up to 2 days)

Full Eligibility Criteria

Inclusion criteria:

* 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 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).
* Cohorts L (L-ext), M, and N (metastatic colorectal cancer (mCRC)): Documented Human epidermal growth factor receptor 2 (HER2) overexpression/amplification according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) gastric cancer guidelines and according to the result of local testing.
* 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 after HER2-directed treatment for unresectable locally advanced or metastatic disease (For Cohorts D, H, I (I-ext), J (J-ext) - patients must have been pretreated with trastuzumab deruxtecan (T-DXd) and have progressed or have been intolerant to previous T-DXd).
  * For cohorts L, L-ext, M and N documented progression or recurrence of disease during or following their latest line of therapy. Patients must have had at least one prior line of therapy for locally advanced unresectable disease or metastatic disease (adjuvant and neoadjuvant therapy excluded) and documented disease progression or recurrence of disease during or following their latest line of therapy. In the opinion of the Investigator, patients must be unlikely to tolerate or derive clinically meaningful benefit from further standard of care therapy known to prolong survival.
* 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 Further inclusion criteria apply.

Exclusion criteria:

* Previous treatment with:

  * Any small molecule HER2 inhibitor in the palliative setting in Cohorts D, E, F, H, L, L-ext, M, and N. In Cohort D allowed in up to 15 patients in each dose level (DL).
  * T-DXd in Cohorts E and F. In Cohort E allowed in up to 15 patients in each DL.
  * trastuzumab emtansine (T-DM1) in the palliative setting in Cohort D and H. In Cohort H allowed in up to 15 patients in each DL.
  * Capecitabine in Cohort D and H. In Cohort D allowed in up to 15 patients in each DL
* Presence of uncontrolled and/or symptomatic brain metastases, or leptomeningeal disease
* 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
* 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 Further exclusion criteria apply.

Trial Locations

• Mayo Clinic-Arizona, Phoenix, Arizona, United States
• The Oncology Institute of Hope and Innovation, Cerritos, California, United States
• Ellison Medical Institute, Los Angeles, California, United States
• Valkyrie Clinical Trials, Los Angeles, California, United States
• University of California Los Angeles, 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
• Mayo Clinic - Florida, Jacksonville, Florida, United States
• H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Metastatic Breast Cancer
• Metastatic Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma
• Esophageal Adenocarcinoma
• Metastatic Colorectal Cancer
• HER2-positive Cancers
• Oncology
• Targeted Therapy
• Cancer Drug Development
• Clinical Trials

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