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NCT Number: NCT07486817

Beamion 44: A Study to Test How Well Zongertinib is Tolerated by People With Advanced Non-small Cell Lung Cancer With HER2 Mutations When Given in Combination With Chemotherapy With or Without Pembrolizumab

This study is open to adults with a type of lung cancer called HER2-mutant non-squamous non-small cell lung cancer (NSCLC) that is advanced or has spread. People who have a tumor with a HER2 mutation and have not received previous treatment for their lung cancer can participate in the study. The purpose of this study is to find out how well a medicine called zongertinib is tolerated in people with this type of lung cancer, when combined with chemotherapy, with or without pembrolizumab. Zongertinib works by targeting and blocking HER2, a protein involved in cancer cell growth.

Participants are put into two groups randomly, which means by chance. One group gets zongertinib tablets combined with platinum-based chemotherapy. The other group gets the same treatment plus an additional medicine called pembrolizumab. Chemotherapy and pembrolizumab are given as an infusion into a vein. Participants take zongertinib by mouth once a day, while chemotherapy is given every 3 weeks for up to 3 months, followed by maintenance treatment for up to 2 years.

Pembrolizumab is given every 3 weeks for up to 2 years.

This study does not have a fixed duration. Participants can receive some of the study treatments for up to about 2 years and may continue to take zongertinib as long as they benefit from treatment and can tolerate it. During this time, they visit the study site regularly. Doctors regularly check the size of the tumor and whether it has spread. They also monitor participants' health and take note of any unwanted effects.

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Key information

Conditions

Lung Cancer, Non-squamous, Non-small Cell Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Royal North Shore Hospital, St Leonards, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)
  • Histologically or cytologically confirmed diagnosis of an advanced and/or metastatic non-squamous non-small cell lung cancer (NSCLC)
  • Documented activating human epidermal growth factor receptor 2 (HER2) mutation as per existing local lab result
  • An archival tumor tissue sample must be submitted to the central laboratory after randomization to retrospectively confirm the HER2 status
  • Patients who have not received any systemic treatment for unresectable, locally advanced or metastatic disease
  • Presence of at least one measurable non-Central Nervous System (CNS) lesion according to response evaluation criteria in solid tumors (RECIST) 1.1
  • Eligible to receive treatment with the selected platinum based doublet chemotherapy and pembrolizumab in accordance with the summary of product characteristics (SmPC)/Product Information
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 Further inclusion criteria apply.

Exclusion criteria

  • Tumors with targetable alterations with approved available therapy
  • Presence or history of leptomeningeal disease
  • Radiotherapy within 4 weeks prior to treatment start with exception of palliative radiotherapy to regions other than the chest if completed at least 2 weeks prior to treatment start
  • Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening
  • 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
  • Previous therapy with a HER2-directed agent
  • History or presence of cardiovascular abnormalities which are considered as clinically relevant by the investigator. Myocardial infarction, stroke, or pulmonary embolism within 6 months prior to randomization Further exclusion criteria apply.

Treatment and study plan

Zongertinib

Drug

Zongertinib

Other names: Hernexeos®

Cisplatin

Drug

Cisplatin

carboplatin

Drug

Carboplatin

Pemetrexed

Drug

Pemetrexed

Pembrolizumab

Drug

Pembrolizumab

Primary outcomes

  1. Occurrence of discontinuation and/or prolonged interruption (>7 days) of zongertinib due to treatment-related adverse events (AEs) in the first 2 cycles of treatment

    Time frame: up to 6 weeks

Secondary outcomes

  1. Occurrence of serious adverse events (SAE) during the on-treatment period

    Time frame: up to 1.5 years

  2. Occurrence of dose reduction of zongertinib

    Time frame: up to 1.5 years

  3. Occurrence of discontinuation and/or prolonged interruption (>7 days) of zongertinib due to treatment-related AEs during the on-treatment period

    Time frame: up to 1.5 years

  4. Occurrence of Grade ≥3 non-hematological AE during the on-treatment period

    Time frame: up to 1.5 years

  5. Occurrence of combination limiting toxicities (CLTs) during the on-treatment period

    Time frame: up to 1.5 years

    Specific adverse events (AEs) are classified as combination limiting toxicities (CLTs) in the study protocol, e.g.:

    • laboratory parameters that exceed predefined limits as defined in the study protocol *
    • Treatment-related death (other than death related to progressive disease)
    • Any AE which causes an interruption or delay to treatment with zongertinib of greater than 7 days
    • Any AE that requires treatment discontinuation of zongertinib in accordance with the study protocol

  6. Objective response (OR) according to Response evaluation criteria in solid tumors (RECIST) 1.1 as assessed by the investigator

    Time frame: up to 1.5 years

    OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) from date of randomization until the earliest of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent

  7. Time to OR, defined as the time from date of randomization to first documented confirmed CR or PR among patients with OR as determined by investigator assessment per RECIST 1.1

    Time frame: up to 1.5 years

  8. Duration of OR (DoR), defined as the time from first documented confirmed CR or PR until disease progression or death among patients with OR as determined by investigator assessment per RECIST 1.1

    Time frame: up to 1.5 years

  9. Progression-free survival (PFS), defined as the time from randomization until tumor progression according to RECIST 1.1 as assessed by the investigator, or death from any cause, whichever occurs earlier

    Time frame: up to 1.5 years

  10. Time on treatment (ToT), defined as the time from first dose of study treatment until zongertinib treatment discontinuation or death

    Time frame: up to 1.5 years

Study contacts

Contact information is provided by the study sponsor or research team.

Boehringer Ingelheim

CONTACT

[email protected]

18002430127

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

Beamion 44: A Randomized, Open-label, Multi-center Phase IIa Platform Trial to Evaluate the Safety and Tolerability of Zongertinib Plus Platinum-based Doublet Chemotherapy With or Without Pembrolizumab (and Potential Other Combinations) in Treatment-naïve Patients With Locally Advanced/Metastatic Non-squamous NSCLC With Activating HER2 Mutations

Important dates

Study start
2026
Primary completion
2027
Study completion
2029
First posted
Mar 23, 2026
Registry last updated
Jul 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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