Recruiting NCT06452277

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)

Phase III Interventional Advanced Non-small Cell Lung Cancer, HER2 Mutation

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Sevabertinib, Pembrolizumab, Cisplatin, Carboplatin.
Who it may be relevant to: Registry conditions: Advanced Non-small Cell Lung Cancer, HER2 Mutation. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Belgium +31
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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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

Overview

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 is a group of lung cancers that have spread to nearby tissues or to other parts of the body or that are unlikely to be cured or controlled with currently available treatments. HER2 is a protein that helps cells to grow and divide. A damage (also called mutation) to the building plans (genes) for this protein in cancer cells leads to a production of abnormal HER2 and therefore abnormal cell growth and division. The study treatment, sevabertinib, is expected to block the mutated HER2 protein which may stop the spread of NSCLC. The main purpose of this study is to learn how well sevabertinib works and how safe it is compared with standard treatment, in participants who have advanced NSCLC with specific genetic changes called HER2 mutations. The study participants will receive one of the study treatments: * Sevabertinib twice every day as a tablet by mouth, or * Standard treatment in cycles of 21 days via infusion ("drip") into the vein. * 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 receiving the standard treatment has their disease get worse (this is called "disease progression"), they may have the opportunity to switch ("cross over") to receive sevabertinib. * 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 doctors and their study team will: * take imaging scans, including CT, PET, MRI, and X-rays, of different parts of the body to study the spread of cancer * check the overall health of the participants by performing tests such as blood and urine tests, and checking * heart health using an electrocardiogram (ECG) * perform pregnancy tests for women * ask the participants questions about how they are feeling and what adverse events they are having. 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.

Interventions

Drug Sevabertinib
Tablet, oral
Drug Pembrolizumab
Intravenous (IV) infusion
Drug Cisplatin
IV infusion
Drug Carboplatin
IV infusion
Drug Pemetrexed
IV infusion

Primary outcome measures

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

Secondary outcome measures (12)

Overall survival (OS) [Time frame: Up to approximately 4 years.]
Objective response rate (ORR) per RECIST 1.1 as assessed by BICR [Time frame: Up to approximately 4 years]
Progression free survival (PFS) per RECIST 1.1 as assessed by the investigator [Time frame: Up to approximately 4 years]
Objective Response Rate (ORR) per RECIST 1.1 as assessed by the investigator [Time frame: Up to approximately 4 years]
Disease control rate (DCR) per RECIST 1.1 as assessed by BICR [Time frame: Up to approximately 4 years]
Disease control rate (DCR) per RECIST 1.1 as assessed by the investigator [Time frame: Up to approximately 4 years]
Duration of response (DOR) as assessed by BICR [Time frame: Up to approximately 4 years]
Duration of response (DOR) as assessed by the investigator [Time frame: Up to approximately 4 years]
Adverse events per CTCAE v 5.0 (eg. TEAEs, TESAEs) categorized by severity [Time frame: Up to approximately 4 years]
Change from baseline in NSCLC-SAQ total score [Time frame: Up to approximately 4 years]
Change from baseline in NSCLC-SAQ individual domain scores [Time frame: Up to approximately 4 years]
Time to deterioration in NSCLC-SAQ total score [Time frame: Up to approximately 4 years]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment

Study locations

United States · 27 centers

Patty & George Hoag Cancer Center — Newport Beach
UC San Diego Health - Moores Cancer Center — San Diego
UCSF Bakar Precision Cancer Medicine Building - Thoracic Surgery and Oncology — San Francisco
UCLA Health Santa Monica Cancer Care — Santa Monica
The Oncology Institute of Hope and Innovation - Fort Lauderdale 17th Street — Fort Lauderdale
Memorial Cancer Institute at Miramar — Miramar
AdventHealth Cancer Institute Orlando — Orlando
Moffitt Cancer Center - Magnolia Campus — Tampa
… and 19 more centers

China · 25 centers

Cancer Hospital, Chinese Academy of Medical Sciences — Beijing
Beijing Cancer Hospital - Oncology Department — Beijing
Beijing Hospital — Beijing
The People's Liberation Army General Hospital (Beijing 301 Hospital) — Beijing
Beijing chest hospital, Capital Medical University — Beijing
Fujian Cancer Hospital — Fuzhou
Xiamen University - The First Affiliated Hospital — Xiamen
The first Affiliated Hospital of Guangzhou Medical University — Guangzhou
… and 17 more centers

Italy · 18 centers