Recruiting
Phase 3

BAY 2927088

Sponsor:

Bayer

Code:

NCT06452277

Conditions

Advanced Non-small Cell Lung Cancer, HER2 Mutation

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Sevabertinib

Pembrolizumab

Cisplatin

Carboplatin

Pemetrexed

Study Details

Brief summary:

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.

Conditions

Advanced Non-small Cell Lung Cancer, HER2 Mutation

Study ID

NCT06452277

Start date

Aug 28, 2024

Status verified date

Jul 24, 2026

Completion date

Jun 27, 2029

Anticipated

Primary completion date

Oct 28, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

444 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Sevabertinib

Participants will receive sevarbetinib 20 mg BID until disease progression per RECIST v1.1, unacceptable toxicity, or until any other withdrawal criteria.

active comparator: Standard of care (SoC)

Participants will receive SoC (pembrolizumab in combination with platinum-based chemotherapy, in 21-day cycles per the approved labels) until disease progression per RECIST v1.1, unacceptable toxicity, or until any other withdrawal criteria. Participants in the SoC arm will have the opportunity to crossover to receive sevabertinib when they experience disease progression.

Interventions

Sevabertinib

Tablet, oral

Pembrolizumab

Intravenous (IV) infusion

Cisplatin

IV infusion

Carboplatin

IV infusion

Pemetrexed

IV infusion

Primary outcome measure

  • Progression free survival (PFS) per RECIST 1.1 as assessed by BICR [ Time Frame: Up to approximately 2 years ]

Central Contacts and Locations

Central contacts

Bayer Clinical Trials Contact

18888422937clinical-trials-contact@bayer.com

Locations

UCSF Bakar Precision Cancer Medicine Building - Thoracic Surgery and Oncology

Recruiting

San Francisco, California, United States, 94158

UCLA Health Santa Monica Cancer Care

Recruiting

Santa Monica, California, United States, 90404

The Oncology Institute of Hope and Innovation - Fort Lauderdale 17th Street

Recruiting

Fort Lauderdale, Florida, United States, 33316

Piedmont Healthcare - Atlanta

Recruiting

Atlanta, Georgia, United States, 30318

John B. Amos Cancer Center

Recruiting

Columbus, Georgia, United States, 31904

University of Illinois Hospital - Outpatient Cancer Care Center

Recruiting

Chicago, Illinois, United States, 60612

UC Medical Center - Oncology

Recruiting

Cincinnati, Ohio, United States, 45219

Taylor Cancer Research Center

Recruiting

Maumee, Ohio, United States, 43537

Allegheny General Hospital

Recruiting

Pittsburgh, Pennsylvania, United States, 15212

The University of Texas MD Anderson Cancer Center - Texas Medical Center

Recruiting

Houston, Texas, United States, 77030

Brampton Civic Hospital | Oncology

Recruiting

Brampton, Ontario, Canada, L6R 3J7

Princess Margaret Cancer Centre - University Health Network - Department of Medical Oncology and Hematology

Recruiting

Toronto, Ontario, Canada, M5G 2C4

Jewish General Hospital | Pulmonary Oncology

Recruiting

Montreal, Quebec, Canada, H3T 1E2

More Information

Sponsor

Bayer

Last update posted

Aug 19, 2026

Last verified

Jul 24, 2026

Keywords

  • NSCLC
  • ERBB2 mutation
  • HER2 mutation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Bayer on 2026-08-19.