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NCT06452277Recruiting

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)

Official recordSimplified version

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.

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.

Contacts

The trial team's contact details are shown on request.

See the official trial record
Status
Recruiting
Phase
Phase 3
Study type
Interventional
Countries
Switzerland, France, Germany, Italy, Austria, United States, Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Finland, Greece, Hong Kong, Hungary, Israel, Japan, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Singapore, Slovakia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom
Sponsor
Bayer(Industry)
Protocol no.
22615
Conditions
Advanced Non-small Cell Lung Cancer, HER2 Mutation
Interventions
Drug

Treatments studied

  • Sevabertinib
  • Pembrolizumab
  • Cisplatin
  • Carboplatin
  • Pemetrexed

Locations · 38

  • San Francisco, United StatesUCSF Bakar Precision Cancer Medicine Building - Thoracic Surgery and OncologyRecruiting at this site
  • Santa Monica, United StatesUCLA Health Santa Monica Cancer CareRecruiting at this site
  • Fort Lauderdale, United StatesThe Oncology Institute of Hope and Innovation - Fort Lauderdale 17th StreetRecruiting at this site
  • Atlanta, United StatesPiedmont Healthcare - AtlantaRecruiting at this site
  • Columbus, United StatesJohn B. Amos Cancer CenterRecruiting at this site
  • Chicago, United StatesUniversity of Illinois Hospital - Outpatient Cancer Care CenterRecruiting at this site
  • Cincinnati, United StatesUC Medical Center - OncologyRecruiting at this site
  • Maumee, United StatesTaylor Cancer Research CenterRecruiting at this site
  • Pittsburgh, United StatesAllegheny General HospitalRecruiting at this site
  • Houston, United StatesThe University of Texas MD Anderson Cancer Center - Texas Medical CenterRecruiting at this site
  • Fortaleza, BrazilPronutrir Fortaleza - CERecruiting at this site
  • Brasília, BrazilCentro Paulista de Oncologia (CPO) - Sao Paulo - Faria LimaRecruiting at this site
  • Recife, BrazilRede DoR Recife - PERecruiting at this site
  • Natal, BrazilLiga Norte Riograndense Contra o Cancer | Centro de Pesquisa ClínicaRecruiting at this site
  • Blumenau, BrazilCentro de Pesquisa da Clínica de Oncologia ReichowRecruiting at this site
  • Bauru, BrazilNAIC - Instituto do CancerRecruiting at this site
  • Jaú, BrazilFundacao Pio XII - Hospital de Cancer de BarretosRecruiting at this site
  • São Paulo, BrazilHospital Sirio LibanesRecruiting at this site
  • São Paulo, BrazilA Beneficencia Portuguesa de Sao Paulo - Hospital BP MiranteRecruiting at this site
  • São Paulo, BrazilIrmandade Santa Casa de Misericordia de Porto Alegre | OncologyRecruiting at this site
  • Sofia, BulgariaMultiprofile Hospital for Active Treatment "Sveta Sofia"Recruiting at this site
  • Brampton, CanadaBrampton Civic Hospital | OncologyRecruiting at this site
  • Toronto, CanadaPrincess Margaret Cancer Centre | Medical Oncology and HematologyRecruiting at this site
  • Montreal, CanadaJewish General Hospital | Pulmonary OncologyRecruiting at this site
  • Brno, CzechiaMasarykova Univerzita - Masarykuv Onkologicky Ustav (MOU) - Klinika Komplexni Onkologicke Pece (KKOP)Recruiting at this site
  • Hong Kong, Hong KongPrince of Wales HospitalRecruiting at this site
  • Hong Kong, Hong KongQueen Elizabeth Hospital Hong KongRecruiting at this site
  • Sapporo, JapanHokkaido University HospitalRecruiting at this site
  • Matosinhos Municipality, PortugalHospital Pedro Hispano | Clinical Research CenterRecruiting at this site
  • Lisbon, PortugalCHULN - Hospital Pulido ValenteRecruiting at this site

In total, worldwide, 38 of the 279 sites listed in the registry are recruiting; the other 241 are not currently recruiting.

Site status per the ClinicalTrials.gov registry (last update posted: October 15, 2026).

This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.

+ 8 more locations

Other identifiers

  • 2024-511319-91-00 · other identifier

See also

Other versions

These results are indicative and do not replace medical advice — discuss them with your doctor.