Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 3
Bayer (Voir sur ClinicalTrials)
août 2024
juin 2029
21 août 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 10/04/2025 13:12:07 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | David PLANCHARD | 05/08/2026 14:30:04 | Contacter | ||
| HOPITAL FOCH | Jaafar BENNOUNA | 11/05/2026 07:26:34 | Contacter | ||
Critères
Tous
- 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.