A Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)

Recruiting now · Phase 3

Conditions studied: Advanced Non-small Cell Lung Cancer, HER2 Mutation

In brief

Researchers are looking for a better way to treat people who have advanced non-small cell lung cancer (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 cells 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, sevabertinib, 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 sevabertinib 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: * Sevabertinib twice every day as a tablet by mouth, or * Standard treatment in cycles of 21 days via infusion ("drip") into the vein. * Participants will continue their assigned treatment for as long as they benefit from it and do not experience severe side effects, or until they or their doctor decide to stop treatment. When a participant receiving the standard treatment has their disease get worse (this is called "disease progression"), they may have the opportunity to switch ("cross over") to receive sevabertinib. * Participants who switch to sevabertinib will continue this treatment until their disease gets worse again, they have side effects that are too severe, or they or their doctor decide to stop treatment. During the study, the doctors and their study team will: * take imaging 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 blood and urine tests, 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.

Key facts

Study ID: NCT06452277
Run by: Bayer
People needed: 444
Starts: 2024-08-28
Expected to finish: 2029-06-27
Last updated by the study team: 2026-07-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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 consent.
Documented histologically or cytologically confirmed locally advanced non-squamous NSCLC, not suitable for definitive therapy or metastatic non-squamous NSCLC at screening (small cell or mixed histologies are excluded) (Stage III-IV NSCLC).
Documented activating HER2 mutation in the tyrosine kinase domain (TKD) assessed by tissue 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.

You may not qualify if…

Known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for five years since initiation of that therapy. Exception: the following cancer types are acceptable within five years if curatively treated or under surveillance:
a. in situ cancers of cervix, breast, or skin,
b. superficial bladder cancer (Ta, Tis and T1),
c. limited-stage prostate cancer,
d. basal or squamous cancers of the skin.
Tumors with targetable alterations with approved available therapy, with the exception of HER2 mutation in the TKD.
Inability to discontinue treatment with chronic systemic corticosteroids. Participants who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable, provided that the dose is stable for >4 weeks prior to planned start of study intervention.
Pre-existing peripheral neuropathy that is Grade ≥2 by CTCAE (v5.0).
History of severe hypersensitivity reaction to treatment with a monoclonal antibody.
Prior radiotherapy outside of the brain within 21 days before of planned start of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.

Where it is running

NSW Health - Blacktown Hospital — Blacktown, New South Wales, Australia (enrolling)
University of the Sunshine Coast — Buderim, Queensland, Australia (enrolling)
The University of Texas MD Anderson Cancer Center - Texas Medical Center — Houston, Texas, United States (enrolling)
The Oncology Institute of Hope and Innovation - Fort Lauderdale 17th Street — Fort Lauderdale, Florida, United States (enrolling)
Concord Repatriation General Hospital - Medical Oncology Clinical Trials Unit — Concord, New South Wales, Australia (enrolling)
Calvary Mater Hospital Newcastle - Oncology — Waratah, New South Wales, Australia (enrolling)
Moffitt Cancer Center - Magnolia Campus — Tampa, Florida, United States (enrolling)
UC San Diego Health - Moores Cancer Center — San Diego, California, United States (enrolling)
Piedmont Healthcare - Atlanta — Atlanta, Georgia, United States (enrolling)
John B. Amos Cancer Center — Columbus, Georgia, United States (enrolling)
UCSF Bakar Precision Cancer Medicine Building - Thoracic Surgery and Oncology — San Francisco, California, United States (enrolling)
Memorial Cancer Institute at Miramar — Miramar, Florida, United States (enrolling)
UM Greenebaum Comprehensive Cancer Center — Baltimore, Maryland, United States (enrolling)
AdventHealth Cancer Institute Orlando — Orlando, Florida, United States (enrolling)
Profound Research -OMG - TriAtria Cancer Center — Farmington Hills, Michigan, United States (enrolling)
Profound Research - OMG - Royal Oak Cancer Center — Royal Oak, Michigan, United States (enrolling)
M Health Fairview Masonic Cancer Clinic - Clinics and Surgery Center — Minneapolis, Minnesota, United States (enrolling)
UCLA Health Santa Monica Cancer Care — Santa Monica, California, United States (enrolling)
UC Medical Center - Oncology — Cincinnati, Ohio, United States (enrolling)
Taylor Cancer Research Center — Maumee, Ohio, United States (enrolling)
Providence Cancer Institute - Franz Clinic — Portland, Oregon, United States (enrolling)
Providence Oncology and Hematology Care Clinic Westside — Portland, Oregon, United States (enrolling)
Allegheny General Hospital — Pittsburgh, Pennsylvania, United States (enrolling)
University of Illinois Hospital - Outpatient Cancer Care Center — Chicago, Illinois, United States (enrolling)
Austin Hospital - Olivia Newton John Cancer Research Institute — Heidelberg, Victoria, Australia (enrolling)

Full record on ClinicalTrials.gov

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