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RecruitingPhase 3

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)

A Phase 3 Open-label, Randomized, Active-controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Orally Administered BAY 2927088 Compared With Standard of Care as a First-line Therapy in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) With HER2-activating Mutations

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study compares sevabertinib with standard treatment to see how well it works and how safe it is. It is for adults with advanced non-small cell lung cancer (NSCLC) that has a specific HER2 gene change. Sevabertinib is a pill designed to block the changed HER2 protein and may slow or stop cancer growth.

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 means lung cancer that has spread nearby or to other parts of the body or is unlikely to be controlled with current treatments. HER2 is a protein that helps cells to grow and divide. Sometimes, cancer cells have a damaged HER2 gene. This is called a mutation. This mutation can lead to an abnormal HER2 protein which may cause cancer cells to grow and divide too quickly. The study treatment, sevabertinib, is designed to block the mutated HER2 protein and may help slow or stop the cancer from growing. The main purpose of this study is to find out how well sevabertinib works and how safe it is, compared with standard treatment in participants with advanced NSCLC with a HER2 mutation. The study participants will receive one of the study treatments: * Sevabertinib as a tablet taken by mouth twice a day * Standard approved treatment for this condition given by infusion into a vein every 21 days 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 assigned to the standard treatment has their cancer gets worse, they may have the opportunity to switch to receive sevabertinib. This switch is called a crossover. 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 research team will: * do scans such as CT, PET, MRI, or X-rays to check the cancer * Check the overall health of the participants by performing tests such as blood and urine tests and checking heart health using an electrocardiogram and echocardiogram. * do pregnancy tests when needed * ask how the participants are feeling and whether they have had any adverse events or other health problems 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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be at least 18, or the legal age to consent if it is higher in your country.
  • Have confirmed stage III or IV non-squamous NSCLC, a type of lung cancer. It must have spread nearby and not be suitable for treatment meant to cure it, or have spread to other parts of the body.
  • Have a tissue test showing a HER2 gene change that makes the protein more active in an area called the tyrosine kinase domain (TKD). The test must come from a qualified lab.
  • Have had no treatment that travels through the body for advanced or spreading lung cancer, and no treatment targeting HER2 exon 20 insertion changes. Treatment before or after surgery is allowed if it ended at least 12 months before screening.
  • Be able to receive pemetrexed with cisplatin or carboplatin (chemotherapy drugs), plus pembrolizumab.

Who can't join

  • Have had another cancer, unless treatment meant to cure it began at least 5 years ago and it has not returned. Some early cancers of the cervix, breast, skin, bladder, or prostate are allowed sooner if treated to cure them or being watched.
  • Have another tumor gene change with an approved, available treatment, apart from the required HER2 TKD change.
  • Cannot stop regular steroid treatment that affects the whole body. Occasional inhalers, inhaled steroids, and local steroid shots are allowed. Steroids that replace missing hormones are allowed if the dose has been stable for more than 4 weeks.
  • Have moderate or worse nerve damage outside the brain and spinal cord, which may cause numbness, tingling, or pain.
  • Have had a severe allergic reaction to a monoclonal antibody treatment, a type of lab-made protein medicine.
  • Have had radiation outside the brain within 21 days before the planned study treatment start. You must also have recovered from all radiation side effects and not need steroids.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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 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. Exclusion Criteria: * 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.

Study sites (25)

CA

FL

GA

IL

  • University of Illinois Hospital - Outpatient Cancer Care Center · Chicago, IL 60612More trials in Chicago
  • The University of Chicago Medical Center - Hyde Park - Hematology & Oncology · Chicago, IL 60637More trials in Chicago

MA

MD

MI

MN

NY

OH

OR

PA

TX

  • University Hospital Simmons Cancer Center Lung/Head Neck Clinic · Dallas, TX 75235More trials in Dallas
  • The University of Texas MD Anderson Cancer Center - Texas Medical Center · Houston, TX 77030More trials in Houston