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Taking peoplePhase 3

Sevabertinib compared with standard treatment for advanced lung cancer with HER2 mutation

Tests sevabertinib tablets against standard treatment in adults with advanced lung cancer.

Key facts

Who runs it
Bayer
Where
Avellino, Aviano, Bologna, Florence, Lecce, Meldola, Milan, Orbassano, Padova, Palermo, Rome, Rozzano, and Verona, ItalySee the 16 sitesAlso in 35 other countries, 250 sites
Registry title
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)
Status
Recruiting
Phase
Phase 3
People taking part
444 people, planned
Started
28 Aug 2024
Expected to end
27 Jun 2029
Type of study
Interventional, 2 groupsOne group gets an existing treatment, for comparison.
Treatments tested
  • Sevabertinib
  • Pembrolizumab
  • Cisplatin
  • Carboplatin
  • Pemetrexed
Record updated
4 November 2026

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults with advanced non-squamous non-small cell lung cancer (NSCLC) that has a HER2 mutation and has not yet had drug treatment for advanced disease.

Age
18 years or older (or above the legal age of consent where that is higher than 18)
Sex
All sexes can join.
Disease stage
Locally advanced non-squamous NSCLC that cannot be treated with definitive therapy, or metastatic non-squamous NSCLC (Stage III-IV). Small cell or mixed types cannot join.
Earlier treatment
No earlier systemic treatment for locally advanced or metastatic disease. No earlier HER2 ex20ins-targeted therapy (for example poziotinib, trastuzumab deruxtecan). Treatment given before or after surgery must have ended at least 12 months before screening.
Biomarker or test result
A documented activating HER2 mutation in the tyrosine kinase domain, found by a tissue test in a certified or accredited local laboratory.

Main reasons for not taking part

  • Another cancer in the past 5 years, apart from a few listed types that were treated or are under watch
  • Cancer with another changed gene that has an approved treatment (other than HER2 in the tyrosine kinase domain)
  • Cannot stop long-term systemic corticosteroids
  • Existing nerve damage in hands or feet of Grade 2 or higher
  • Radiotherapy outside the brain within 21 days before the planned start of treatment

The registry criteria, word for word

Show all 11 criteriaShow less

Who can take part

  • 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

Who cannot take part

  • 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
  • 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
  • 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
  • Pre-existing peripheral neuropathy that is Grade ≥2 by CTCAE (v5.0)

Check if you might fit

Answer for yourself. This is not a decision: only the study team can say whether you can take part.

  • Which best describes your lung cancer?
  • Has the cancer spread to other parts of the body, or is it too advanced to be removed by surgery?

Where in Italy

Also in 35 other countries, 250 sites

  • AORN San Giuseppe Moscati AvellinoAvellino, ItalyNo longer taking part
  • Centro di Riferimento Oncologico di AvianoAviano, ItalyNo longer taking part
  • Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere ScientificoBologna, ItalyNo longer taking part
  • Azienda Ospedaliero-Universitaria CareggiFlorence, ItalyNo longer taking part
  • Ospedale Vito Fazzi LecceLecce, ItalyNo longer taking part
  • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.lMeldola, ItalyNo longer taking part
  • Fondazione IRCCS - Istituto Nazionale dei TumoriMilan, ItalyNo longer taking part
  • Istituto Europeo di Oncologia s.r.lMilan, ItalyNo longer taking part
  • Ospedale San Raffaele S.r.l.Milan, ItalyNo longer taking part
  • Azienda Ospedaliero-Universitaria San Luigi GonzagaOrbassano, ItalyNo longer taking part
  • Istituto Oncologico VenetoPadova, ItalyNo longer taking part
  • Azienda Ospedaliera Ospedali Riuniti Villa Sofia - CervelloPalermo, ItalyNo longer taking part
  • Fondazione Policlinico Universitario Agostino Gemelli IRCCSRome, ItalyNo longer taking part
  • I.F.O. Istituti Fisioterapici OspitalieriRome, ItalyNo longer taking part
  • Humanitas Mirasole S.p.A.Rozzano, ItalyNo longer taking part
  • Centro Ricerche Cliniche di Verona s.r.l.Verona, ItalyNo longer taking part

About the trial

What the trial wants to find out

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.

Read full original descriptionShow less

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.

The 2 groups in the trial

  • SevabertinibTreatment being tested

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

  • Standard of care (SoC)Existing treatment, for comparison

    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.

    Treatment: Pembrolizumab, Cisplatin, Carboplatin, and Pemetrexed

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov and on the EU's official list of trials (CTIS).
Official title
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
Plain-language title
Sevabertinib compared with standard treatment for advanced lung cancer with HER2 mutationGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 12 November 2026.
Fit questions
Built from NCT06452277, who can take part
Record updated
4 November 2026