A Phase 3 trial of BAY 2927088 compared with standard of care as first-line therapy for advanced non-small cell lung cancer (NSCLC) with HER2 mutations

JRCT ID: jRCT2031240248

Registered date:01/08/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced non-small cell lung cancer
• Date of first enrollment: 01/08/2024
• Target sample size: 278
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Czechia,Japan,Denmark,Japan,Finland,Japan,France,Japan,Germany,Japan,Greece,Japan,Hong Kong,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Republic of Korea,Japan,Mexico,Japan,Netherlands,Japan,Poland,Japan,Portugal,Japan,Singapore,Japan,Spain,Japan,Sweden,Japan,Switzerland,Japan,Taiwan,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: BAY2927088 Tablet, oral
Drug: Pembrolizumab Intravenous (IV) infusion
Drug: Cisplatin IV infusion
Drug: Carboplatin IV infusion
Drug: Pemetrexed IV infusion

Outcome(s)

Primary Outcome

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

Secondary Outcome

Secondary Outcome Measures:
- Overall survival (OS)
- Objective response rate (ORR) per RECIST 1.1 as assessed by BICR
- Progression free survival (PFS) per RECIST 1.1 as assessed by the investigator
- Objective Response Rate (ORR) as assessed by the investigator
- Disease control rate (DCR) per RECIST 1.1 as assessed by BICR
- Disease control rate (DCR) per RECIST 1.1 as assessed by the investigator
- Duration of response (DOR) as assessed by BICR
- Duration of response (DOR) as assessed by the investigator
- Adverse events per CTCAE v 5.0 (eg. TEAEs, TESAEs) categorized by severity
- Change from baseline in NSCLC-SAQ total score
- Change from baseline in NSCLC-SAQ individual domain scores
- Time to deterioration in NSCLC-SAQ total score
- Time to deterioration in NSCLC-SAQ individual domain scores
- Time to deterioration in EORTC QLQ-C30 physical functioning domain score
- Change from baseline in EORTC QLQ-C30 physical functioning domain score
- Change from baseline in EORTC QLQ-C30 global health status/QoL
[ Time Frame: Up to approximately 4 years ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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 of planned start of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.

Related Information

• Primary Sponsor: Tanigawa Takahiko
• Secondary ID(s): NCT06452277