Brief Summary
Researchers are looking for a better way to treat people who have advancedat a late stage, far along non-small cell lung cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs (NSCLC) with specific genetic changes called human epidermal growth factor receptor 2 (HER2) mutations.
Advanced NSCLC is a group of lung cancers that have spread to nearby tissues or to other parts of the body or that are unlikely to be cured or controlled with currently available treatments. HER2 is a protein that helps cellsthe basic structural and functional unit of all living things to grow and divide. A damage (also called mutation) to the building plans (genes) for this protein in cancer cells leads to a production of abnormal HER2 and therefore abnormal cell growth and division.
The study treatment, BAY 2927088, is expected to block the mutated HER2 protein which may stop the spread of NSCLC.
The main purpose of this study is to learn how well BAY 2927088 works and how safe it is compared with standard treatment, in participants who have advanced NSCLC with specific genetic changes called HER2 mutations.
The study participants will receive one of the study treatments:
- BAY 2927088 twice every day as a tablet by mouth, or
- Standard treatment in cycles of 21 days via infusionto slowly introduce/give fluid into a vein (“drip”) into the veina blood vessel that carries deoxygenated blood to the heart to get oxygen. The treatment will continue for as long as participants benefit from it without any severe side effects or until they or their doctor decide to stop the treatment.
During the study, the doctors and their study team will:
- take imagingtests that create detailed images of areas inside the body scans, including CT, PET, MRI, and X-rays, of different parts of the body to study the spread of cancer
- check the overall health of the participants by performing tests such as bloodthe red bodily fluid that transports oxygen and other nutrients around the body and urine teststesting done to measure the levels of certain substances in the urine, and checking
- heart health using an electrocardiogram (ECG)
- perform pregnancy tests for women
- ask the participants questions about how they are feeling and what adverse events they are having.
An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatment.
Intervention / Treatment
- Drug: BAY2927088
- Drug: Pembrolizumab
- Drug: Cisplatin
- Drug: Carboplatin
- Drug: Pemetrexed
Inclusion Criteria:
- Participant must be ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signing the informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..
- Documented histologically or cytologically confirmed locally advanced non-squamous NSCLC, not suitable for definitive therapy or metastatic non-squamous NSCLC at screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening (small cell or mixed histologies are excluded) (Stage III-IV NSCLC).
- Documented activating HER2 mutation in the tyrosine kinase domain (TKD) assessed by tissuea group of cells that work together to perform a function molecular test in a CLIA-certified (US sites) or an equally accredited (outside of the US) local laboratory. However, participants may be included at the discretion of the investigator if the laboratory performing the assay is not CLIA or similar certified but the laboratory is locally accredited.
- No prior systemic therapy for locally advanced or metastatic disease. No prior treatment with a HER2 ex20ins-targeted therapy (e.g. poziotinib, trastuzumab deruxtecan). Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the start of screening.
- Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the SmPC/Product Information.