Zongertinib with cisplatin or carboplatin and pemetrexed, with or without pembrolizumab, for patients with locally advanced or metastatic non-squamous non-small cell lung cancer with HER2 mutations

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What is this study about?

This clinical trial is studying locally advanced or metastatic non-small cell lung cancer with HER2 mutations, which are changes in a gene that can help cancer grow. The treatment being tested is zongertinib (also called BI 1810631) taken by mouth, given together with standard chemotherapy medicines such as pemetrexed, cisplatin, or carboplatin, and in some study groups also with pembrolizumab. The purpose of the study is to see how safe this treatment combination is and how well it is tolerated.

The study compares different treatment combinations in adults who have not yet received treatment for this cancer. Treatment is given in cycles, with medicine taken or infused over repeated visits. After the first part of treatment, the study continues with follow-up while treatment is ongoing, to watch for side effects and other health changes. Some people may receive different combinations as part of the study design.

Pemetrexed, cisplatin, and carboplatin are chemotherapy medicines, which are drugs used to kill cancer cells. Pembrolizumab is an immunotherapy medicine, which helps the body’s own defense system attack cancer cells. Intravenous means the medicine is given through a vein.

Who Can Join the Study?

Be at least 18 years old, or be above the legal age of consent in the country where the study is done if that age is higher than 18.
Have a confirmed diagnosis of advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). “Advanced” means the cancer has grown beyond its original area, and “metastatic” means it has spread to other parts of the body. “Non-squamous” means the cancer is not the squamous cell type.
Have a documented activating HER2 mutation based on a local laboratory result. A mutation is a change in a gene, and HER2 is a gene that can help cancer cells grow.
Provide an archival tumor tissue sample after randomization so a central laboratory can later confirm the HER2 result. An archival sample means tissue that was already removed and stored from a previous procedure.
Have not received any systemic treatment for unresectable, locally advanced, or metastatic disease. “Systemic treatment” means treatment that works throughout the body, such as chemotherapy or targeted therapy.
Have at least one measurable non-CNS lesion according to RECIST 1.1. A lesion is an area of cancer, and measurable means it can be measured on scans. “Non-CNS” means outside the brain and spinal cord. RECIST 1.1 is a standard way doctors measure tumor size in studies.
Be able to receive treatment with the chosen platinum-based doublet chemotherapy and pembrolizumab according to the product information. Platinum-based doublet chemotherapy means two cancer medicines are given together, and one contains a platinum drug. Pembrolizumab is a medicine that helps the immune system attack cancer.
Have an ECOG performance status of 0 or 1. ECOG is a scale that shows how well a person can do daily activities. A score of 0 means fully active, and 1 means only slightly limited in physical activity.
Meet any other inclusion requirements not listed here.

Who Cannot Join the Study?

The tumor has a targetable alteration, meaning a change in the cancer that already has an approved treatment available.
There is or was leptomeningeal disease, which means cancer cells in the thin layers of tissue that cover the brain and spinal cord.
The patient had radiotherapy (treatment with radiation) within 4 weeks before starting the study, except for palliative radiotherapy to areas other than the chest if it was finished at least 2 weeks before treatment starts.
The patient had major surgery within 4 weeks before randomization, or major surgery is planned within 6 months after screening. Randomization means being assigned to a treatment group by chance, and screening means the tests done before joining the study.
There is any past or current medical condition that, in the investigator’s opinion, could make it hard to follow the study rules or could interfere with checking whether the treatment is safe and works well.
The patient has had previous treatment with a HER2-directed agent, which is a medicine that targets the HER2 protein on cancer cells.
There are heart or blood vessel problems that the investigator considers clinically important.
The patient had a myocardial infarction (heart attack), stroke, or pulmonary embolism (a blood clot in the lungs) within 6 months before randomization.
Other exclusion rules also apply.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Institut Curie – Site Paris	Paris	France

Other Sites

Site Name	City	Country
Virgen del Rocío University Hospital	Sevilla	Spain
Thoraxklinik Heidelberg gGmbH	Heidelberg	Germany
Hospital Universitario 12 De Octubre	Madrid	Spain
Hzjgtlwb Voci draonaon	Barcelona	Spain
Ubvcuhgssx Hogfgrpw Czuakwv	Cologne	Germany
Chwlqg Lmtv Bqqqnn	Lyon	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	01.06.2026
Germany	Recruiting	01.06.2026
Spain	Recruiting	01.06.2026

Trial locations

Investigated drugs:

Pemetrexed is a cancer medicine given through a vein. In this trial, it is used as part of a standard chemotherapy combination to help treat advanced non-squamous lung cancer.

Zongertinib is the main study medicine taken by mouth. It is designed to target HER2 changes in the cancer cells, with the goal of slowing or stopping cancer growth while the study checks how safe and tolerable it is.

Cisplatin is a chemotherapy medicine given through a vein. In this trial, it is one of the platinum-based medicines used with zongertinib to attack cancer cells and help control the disease.

Carboplatin is a chemotherapy medicine given through a vein. It is another platinum-based treatment option in the study, used with zongertinib to treat the cancer and to compare how well the combination is tolerated.

Pembrolizumab is an immunotherapy medicine given through a vein. In this trial, it may be added to zongertinib and chemotherapy to help the immune system recognize and fight the cancer cells more effectively.

Investigated diseases:

Non-small cell lung cancer

Non-Small Cell Lung Cancer – A cancer that starts in the tissues of the lung and includes several common types, such as adenocarcinoma and squamous cell carcinoma. It usually begins as a growing mass in the lung and can spread to nearby lymph nodes and other parts of the body. In locally advanced disease, it has grown into nearby structures or lymph nodes near the chest. In metastatic disease, it has spread to distant organs or tissues beyond the lung.

Trial ID:

2025-523567-38-00

Protocol code:

1479-0044

Trial Phase:

Therapeutic exploratory (Phase II)

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Zongertinib with cisplatin or carboplatin and pemetrexed, with or without pembrolizumab, for patients with locally advanced or metastatic non-squamous non-small cell lung cancer with HER2 mutations

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?