Beamion LUNG 2: A Phase III, Open-label, Randomized, Active-controlled, Multi-centre Trial Evaluating Orally Administered Zongertinib (BI 1810631) Compared With Standard of Care as First-line Treatment in Patients With Unresectable, Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Harbouring HER2 Tyrosine Kinase Domain Mutations

Plain English Summary

Beamion LUNG-2: A Study to Test Whether Zongertinib (BI 1810631) Helps People With Advanced Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment is a Phase 3 clinical trial sponsored by Boehringer Ingelheim studying Lung Cancer, Non-squamous, Non-small Cell. Tests zongertinib, a new drug, to see if it can slow down the growth of advanced lung cancer better than the current standard treatment. For patients with advanced non-squamous non-small cell lung cancer who have HER2 mutations and have not yet received any treatment for their cancer. Participation involves taking zongertinib or receiving standard treatment with pembrolizumab, pemetrexed, and cisplatin or carboplatin every 3 weeks for up to 70 months. Alternative treatments include the current standard of care, pembrolizumab plus platinum-pemetrexed chemotherapy. The trial aims to enroll 416 participants.

Official Summary

This study is open to adults 18 years and older with advanced or metastatic non-small cell lung cancer. People can join the study if they have tumours with HER2 mutations and have not yet received any systemic therapy including chemotherapy for advanced or metastatic lung cancer. The purpose of this study is to find out whether a medicine called zongertinib (BI 1810631) can slow down the worsening of advanced non-small cell lung cancer better than the standard treatment available. Zongertinib may slow cancer cell growth by inhibiting HER2. This would prolong cancer re-occurrence and increase survival. Current standard treatment is pembrolizumab plus platinum-pemetrexed chemotherapy. Participants are put into 2 groups by chance. One group receives zongertinib at regular times throughout the study and the other group receives infusions of pembrolizumab, pemetrexed and cisplatin or carboplatin (pembrolizumab plus platinum-pemetrexed chemotherapy) into a vein. Participants may be in the study up to a maximum of 70 months. During this time, they visit the study site about every 3 weeks for study procedures. The doctors regularly check the size of the tumour with a CT or MRI scan, at the beginning of the study and every 6 weeks. After 18 months they check the tumour size every 12 weeks. Doctors regularly check whether the cancer has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects. The time it takes for the cancer to worsen is compared between the 2 groups to see whether the treatment works. The participants also fill in questionnaires about their symptoms and quality of life.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if 18 years or older, have advanced or metastatic non-small cell lung cancer, and have HER2 mutations. Not eligible if have had other cancers in the last 5 years, have other treatable cancers, or have severe health issues. Age: 18 years or older. Health: Must not have had other cancers in the last 5 years, must not have other treatable cancers, and must not have severe health issues. This trial is studying Lung Cancer, Non-squamous, Non-small Cell, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures, such as progression-free survival, will help determine if zongertinib can significantly improve the time before the cancer worsens for patients. The specific primary outcome measures are: Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 determined by blinded central independent review (up to 4 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 is crucial as it aims to fill the treatment gap for patients with HER2 mutated lung cancer by evaluating a new drug that could potentially improve survival and quality of life. 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 Lung Cancer, Non-squamous, Non-small Cell, where improved treatment options are needed.

Investor Insight

The market for targeted therapies for lung cancer is large, with many competitors, but this trial could lead to a new treatment option if successful. 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 you have HER2 mutations in your lung cancer and if you are eligible for this trial. You will visit the study site every 3 weeks for about 70 months, and your cancer will be monitored regularly. 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: 416 participants

Interventions

• DRUG: zongertinib — zongertinib
• DRUG: pembrolizumab — pembrolizumab
• DRUG: cisplatin — platinum-pemetrexed chemotherapy
• DRUG: carboplatin — platinum-pemetrexed chemotherapy
• DRUG: pemetrexed — platinum-pemetrexed chemotherapy

Primary Outcomes

• Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 determined by blinded central independent review (up to 4 years and 5 months)

Secondary Outcomes

• Key secondary endpoint: Overall Response (OR) according to RECIST 1.1 determined by blinded central independent review (up to 53 months)
• Key secondary endpoint: Change from baseline to Week 25 of Non-small cell lung cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score (at baseline, at week 25)
• Key secondary endpoint: Overall Survival (OS) (up to 53 months)
• Duration of response (DoR), determined by blinded central independent review (up to 53 months)
• PFS determined by blinded central independent review (up to 53 months)

Full Eligibility Criteria

Inclusion criteria:

1. Signed and dated written informed consent form (ICF) in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
2. 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.
3. Histologically or cytologically confirmed diagnosis of an advanced and/or metastatic non-squamous Non-small cell lung cancer (NSCLC).
4. Documented Human epidermal growth factor receptor 2 (HER2) mutation in the Tyrosine kinase domain (TKD) as per local lab results.
5. An archival tumor tissue sample must be submitted to the central laboratory after inclusion of the patient to retrospectively confirm the HER2 status. If no archival tissue is available, this may be acceptable in exceptional cases after written agreement with the sponsor.
6. Patients who have not received any systemic treatment for unresectable, locally advanced or metastatic disease and are not eligible for curative therapy.
7. 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.
8. Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the Summaries of Product Characteristics (SmPC)/Product Information.

Further inclusion criteria apply.

Exclusion criteria:

1. Previous or concomitant malignancies other than the one treated in this trial within the last 5 years, 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
2. Tumors with targetable alterations with approved available therapy.
3. Lung-specific intercurrent clinically significant severe illness based on investigators assessment.
4. Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
5. Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening, e.g. hip replacement.
6. Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the test drug.
7. 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, stroke, or pulmonary embolism within 6 months prior to randomization.
8. 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.

Further exclusion criteria apply.

Trial Locations

• Clearview Cancer Institute, Huntsville, Alabama, United States
• Pioneer Research Center - Bullhead City, Bullhead City, Arizona, United States
• Precision NextGen Oncology, Beverly Hills, California, United States
• ClinRé 001-022 (Premier Cancer Care and Infusion Center), Fresno, California, United States
• OPN Healthcare, Inc., Glendale, California, United States
• Scripps Green Hospital, La Jolla, California, United States
• Valkyrie Clinical Trials, Los Angeles, California, United States
• Sharp Memorial Hospital, San Diego, California, United States
• St. Louis Cancer Care, LLP, Bridgeton, Missouri, United States
• Oncology Hematology Associates, Springfield, Missouri, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Lung Cancer, Non-squamous, Non-small Cell
• Lung Cancer, Squamous Cell
• Lung Cancer, Small Cell
• Lung Cancer, Metastatic
• Lung Cancer, Advanced
• Lung Cancer, HER2 Mutated
• Lung Cancer, Non-small Cell
• Lung Cancer, Unresectable

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