Beamion LUNG 2: A Phase III, open-label, randomized, active-controlled, multi-centre trial evaluating orally administered BI 1810631 compared with standard of care as first-line treatment in patients with unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer harbouring HER2 tyrosine kinase domain mutations

JRCT ID: jRCT2071230098

Registered date:04/12/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD mutations
• Date of first enrollment: 15/01/2024
• Target sample size: 270
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,China,Japan,France,Japan,Germany,Japan,Greece,Japan,Hong Kong,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Republic of Korea,Japan,Mexico,Japan,Netherland,Japan,Norway,Japan,Poland,Japan,Portugal,Japan,Singapore,Japan,Spain,Japan,Sweden,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Zongertinib (BI 1810631): Oral administration
Pembrolizumab plus platinum-pemetrexed chemotherapy: intravenous administration

Outcome(s)

• Primary Outcome: PFS according to RECIST 1.1 determined by blinded central independent review. PFS is defined as the time from randomization until tumor progression according to RECIST 1.1 or death from any cause, whichever occurs earlier.

Secondary Outcome

[Key secondary endpoints]
OR according to RECIST 1.1, determined by blinded central independent review, the change from baseline to Week 25 of NSCLC-SAQ total score, and OS. OR is defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to RECIST 1.1 from date of randomization until the earliest of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent. OS is defined as the time from randomization until death from any cause.

[Secondary endpoints]
1) Duration of response (DoR), determined by blinded central independent review. DoR is defined as the time from first documented CR or PR until the earliest of disease progression or death among patients with objective response.
2) For patients with central nervous system (CNS) lesions at baseline: CNS PFS, determined by blinded central independent review. CNS PFS is defined as the time from randomization until tumor progression according to RANO-BM or death from any cause, whichever occurs earlier.
3) Bi-compartmental PFS, determined by blinded central independent review. Bi-compartmental PFS is defined as the time from randomization until tumor progression according to RECIST 1.1 and/or RANO-BM or death from any cause, whichever occurs earlier.
4) For patients with CNS lesions at baseline: CNS OR, determined by blinded central independent review. CNS OR is defined as best overall response of CR or PR, where best overall response is determined according to RANO-BM from date of randomization until the earliest of CNS progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent.
5) Patient reported outcomes (PROs), analyzed as change from baseline to Week 25 of the following PRO domain scores:
- NSCLC-SAQ pain domain score
- NSCLC-SAQ dyspnoea domain score
- NSCLC-SAQ cough domain score
- NSCLC-SAQ appetite domain score
- NSCLC-SAQ fatigue domain score
- EORTC QLQ-C30 physical functioning domain score
6) Occurrence of adverse events (AEs) during the on-treatment period, graded according to CTCAE version 5.0.
7) Occurrence of serious AEs (SAEs) during the on-treatment period, graded according to CTCAE version 5.0.

Key inclusion & exclusion criteria

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

Include criteria

1) Patients 18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the informed consent form (ICF).
2) Histologically or cytologically confirmed diagnosis of advanced and/or metastatic non-squamous NSCLC.
3) Documented HER2 mutation in the TKD as per local lab results preferably by tissue NGS/PCR, but also ctDNA.
4) Availability and willingness to provide a sample of archival formalin-fixed paraffin embedded (FFPE) tumor tissue material.
5) Patients who have not received any systemic treatment for locally advanced or metastatic disease. Prior neoadjuvant and/or adjuvant chemotherapy or immunotherapy is allowed if the treatment was completed more than 6 months prior to trial entry.
6) Presence of at least one measurable lesion according to RECIST 1.1, as determined by the local site investigator/radiology assessment. Patients with asymptomatic (i.e. no clinical [neurological] symptoms) brain lesions are eligible.
7) Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the Summary of Product Characteristics/Product Information.
8) Eastern Cooperative Oncology Group (ECOG) score of 0
or 1.
9) Adequate organ function based on laboratory values.

Exclude criteria

1) Tumors with targetable alterations with approved available therapy.
2) Presence or history of uncontrolled or symptomatic brain, subdural metastases or leptomeningeal disease, unless considered stable by the investigator and local therapy was completed.
3) Lung-specific intercurrent clinically significant severe illness based on investigators assessment
4) Radiotherapy within 4 weeks prior to randomization with exception of palliative radiotherapy completed 2 weeks prior to randomization.
5) Major surgery (major according to the investigators assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening.
6) Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patients ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the test drug.
7) History or presence of cardiovascular abnormalities which are considered as clinically relevant by the investigator. Myocardial infarction, stroke, or pulmonary embolism within 6 months prior to randomization.
8) Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting electrocardiograms.
9) Mean resting corrected QT interval (QTcF) more than 470 msec.
10) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval.
11) Ejection fraction less than 50 percent or the lower limit of normal of the institutional standard, whatever is lower.
12) Active or known pre-existing non-infectious interstitial lung disease/pneumonitis.
13) Any history or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of the trial drug in the opinion of the investigator.

Related Information

• Primary Sponsor: Takeuchi Yoshito