Beamion LUNG-3: A Randomized, Controlled, Multi-center Trial Evaluating Zongertinib as an Adjuvant Monotherapy Compared With Standard of Care in Patients With Early-stage, Resectable Non-small Cell Lung Cancer (Stage II-IIIB) Harboring Tyrosine Kinase Domain Activating HER2 Mutations

Plain English Summary

Beamion LUNG-3: A Study to Test Whether Zongertinib Helps People With Surgically Removed, Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment is a Phase 3 clinical trial sponsored by Boehringer Ingelheim studying Non-small Cell Lung Cancer. This trial tests if zongertinib, a new drug, helps people with early-stage lung cancer live longer without the cancer returning after surgery, compared to standard treatments. It is for adults with non-small cell lung cancer (NSCLC) that has been surgically removed and has a specific genetic change called an HER2 mutation. Participation involves taking zongertinib by mouth daily for up to 3 years or receiving standard treatment (immunotherapy or observation), with regular check-ups and scans for up to 11 years. Alternatives include standard post-surgery treatments like immunotherapy or observation, depending on the doctor's choice. The trial aims to enroll 400 participants.

Official Summary

This study is open to adults 18 years and older who have early-stage non-small cell lung cancer (NSCLC). Their cancer must have a specific change in a gene called HER2. Genes provide the instructions for making proteins, and this change leads to a faulty HER2 protein. People can join if their lung cancer was removed by surgery, and they have already received certain other anti-cancer treatments. The purpose of this study is to find out if a study medicine called zongertinib helps people with this type of cancer live longer without their cancer coming back after surgery, when compared to standard treatment. Zongertinib is being developed to target the faulty HER2 protein, which can cause cancer cells to grow. In this study, participants are assigned by chance to one of two treatment groups, with an equal chance of being in either group. One group takes the study medicine, zongertinib, by mouth once a day for up to 3 years. The other group receives a standard treatment, chosen by their doctor. This standard treatment may be an immunotherapy medicine given by infusion into a vein every 3 or 4 weeks for up to 1 year, or regular check-ups without active study medicine (observation). Participants can be in this study for up to about 11 years. During this time, they visit the study site regularly for check-ups and study-related tests. The frequency of these visits varies depending on their treatment and how long they have been in the study. In addition to visits at the study site, participants in some treatment groups will also have phone calls with the study team every 3 weeks to check on their health between their scheduled visits. Doctors check for any signs of cancer coming back using imaging scans (like CT or MRI scans); these scans are generally done every 3 months for the first 2 years, then every 6 months for the next 3 years, and then yearly. Participants also fill in questionnaires about their overall wellbeing, health and symptoms. Throughout the study, docto

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with early-stage NSCLC that has been removed by surgery. Patients must have a confirmed HER2 gene mutation in their tumor. Individuals must have had their cancer staged as II to IIIB and have good general health and organ function. People with certain other genetic mutations in their cancer, recent major surgery, or specific lung/heart conditions cannot join. This trial is studying Non-small Cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome, disease-free survival, measures how long patients live without their cancer coming back, indicating if zongertinib is more effective than standard care in preventing recurrence. The specific primary outcome measures are: Disease-free survival (DFS) by investigator's assessment (up to 8 years and 5 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 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a need for new treatments in early-stage lung cancer with specific HER2 mutations, aiming to prevent cancer recurrence after surgery. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Non-small Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This Phase 3 trial for zongertinib, targeting a specific mutation in a common cancer, signals a significant market opportunity if successful, with potential for a competitive advantage in the adjuvant Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if zongertinib is a good option for your specific type of lung cancer and HER2 mutation. Understand the time commitment, which can be up to 11 years, including regular clinic visits, scans, and potential phone check-ins. Be prepared for potential side effects and discuss any new or worsening symptoms with your study team immediately. 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: PARALLEL
• Masking: NONE
• Enrollment: 400 participants

Interventions

• DRUG: Zongertinib — Zongertinib
• DRUG: Pembrolizumab — Pembrolizumab
• DRUG: Atezolizumab — Atezolizumab
• DRUG: Durvalumab — Durvalumab
• DRUG: Nivolumab — Nivolumab

Primary Outcomes

• Disease-free survival (DFS) by investigator's assessment (up to 8 years and 5 months)

Secondary Outcomes

• Key secondary endpoint: Overall survival (OS), defined as the time from randomization until death from any cause (up to 8 years and 5 months)
• Occurrence of trial-related Adverse Events (AEs) ≥ Grade 3 from first treatment administration (or from randomization for patients in the observation arm) until the earliest of tumor recurrence or 3 years since treatment start (up to 3 years)

Full Eligibility Criteria

Inclusion criteria:

1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
2. Patients must be ≥18 years old or over the legal age of consent in their country
3. Male or female patients. Women of childbearing potential (WOCBP) must be ready and able to use dual highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information and in the study protocol
4. HER2 mutation: Documented Tyrosine kinase domain (TKD) activating Human epidermal growth factor receptor 2 (HER2) mutations
5. Histology and tumor sample: Histologically confirmed diagnosis of primary NSCLC
6. An archival tumor tissue sample must be submitted to the central laboratory after inclusion of the patient to retrospectively confirm the HER2 status
7. Staging: Pretherapeutic classification not exceeding Stage IIIB
8. Performance status and organ function:

   * Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
   * Adequate organ function based on laboratory values Further inclusion criteria apply.

Exclusion criteria:

1. Diagnosis of NSCLC with mixed histology/positive neuroendocrine markers (synaptophysin/CD56)
2. Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization
3. Treatment with radiation therapy for primary NSCLC
4. Co-occurring actionable mutation with approved targeted therapy (e.g. Epidermal growth factor receptor (EGFR) or Anaplastic lymphoma kinase (ALK))
5. Any investigational drug within 5 half-lives of the compound or any of its related material, if known
6. History or presence of

   * Active or known pre-existing or history of non-infectious interstitial lung disease/pneumonitis
   * Active infectious disease requiring systemic therapy
   * Uncontrolled gastrointestinal disorders affecting drug intake/absorption
   * Previous or concomitant malignancies within the last 3 years, except certain effectively treated cancers
   * Significant and/or uncontrolled cardiovascular abnormalities, QT interval corrected for heart rate by Fridericia formula (QTcF) \>470 msec, or ejection fraction \<50% Further exclusion criteria apply.

Trial Locations

• ClinRé 001-022 (Premier Cancer Care and Infusion Center), Fresno, California, United States
• OPN Healthcare, Inc., Glendale, California, United States
• University of California Irvine, Irvine, California, United States
• Sutter Health, Roseville, California, United States
• University of California San Francisco, San Francisco, California, United States
• Sarcoma Oncology Center, Santa Monica, California, United States
• University of California Los Angeles, Santa Monica, California, United States
• Northern California Kaiser Permanente, Vallejo, California, United States
• George Washington University Cancer Center, Washington D.C., District of Columbia, United States
• Mid Florida Hematology and Oncology Center, Orange City, Florida, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer
• Lung Adenocarcinoma
• HER2-mutated cancers
• Adjuvant therapy
• Oncology
• Cancer immunotherapy
• Targeted cancer therapy
• Tyrosine kinase inhibitors
• Thoracic oncology
• Genomic medicine

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