About Beamion LUNG-2
Trial Overview
Beamion LUNG-2 is a phase 3, open label, randomized, active-controlled study that will enroll 270 patients. After screening, eligible patients will be randomized to receive zongertinib or standard of care treatment (pembrolizumab plus platinum-pemetrexed chemotherapy).
Participants are put into 2 groups by chance. One group receives zongertinib at regular times throughout the study and the other group receives infusions of pembrolizumab, pemetrexed and cisplatin or carboplatin (pembrolizumab plus platinum-pemetrexed chemotherapy) into a vein.
Zongertinib will be orally administered.
Trial Objective
The purpose of this study is to find out whether zongertinib (BI 1810631) can slow down the worsening of advanced non-small cell lung cancer better than the standard treatment available. Zongertinib may slow cancer cell growth by inhibiting HER2. This would prolong cancer re-occurrence and increase survival. Current standard treatment is pembrolizumab plus platinum-pemetrexed chemotherapy.
Zongertinib selectively and covalently binds to the tyrosine kinase domain of mutated HER2 receptors. Selective binding blocks aberrant downstream signaling, while sparing wild-type EGFR signaling, thereby avoiding wild-type EGFR-associated toxicity.
The primary outcome of the Beamion LUNG-2 trial is progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 determined by blinded central independent review. Key secondary outcomes are objective response (OR), the change from baseline to Week 25 of Non-small cell lung cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score, and overall survival (OS). Secondary outcomes include duration of response (DoR), bi-compartmental PFS, patient-reported outcomes, and occurrence of adverse events (AEs) serious AEs (SAEs) during the on-treatment period.
Trial Duration
Participants may be in the study up to a maximum of 70 months. During this time, they visit the study site about every 3 weeks for study procedures. The doctors regularly check the size of the tumour with a CT or MRI scan, at the beginning of the study and every 6 weeks. After 18 months they check the tumour size every 12 weeks.
Treatment in the Beamion LUNG-2 trial will continue until patient’s disease progresses, or until another reason requiring termination of treatment occurs, such as undue toxicity or patient decision. If the patient is randomized to the chemotherapy + pembrolizumab arm, they can receive treatment up to a maximum of 35 cycles because this is the recommended time of treatment according to approved guidelines.
Patients who ended treatment for reasons other than progressive disease will continue tumour assessments until documented disease progression or start of a new anti-cancer therapy.
Key Eligibility Criteria
Patients in the Beamion LUNG-2 trial must be 18 years of age or older with:
Histologically or cytologically confirmed diagnosis of an advanced and/or metastatic non-squamous NSCLC.
Documented HER2 mutation in the Tyrosine kinase domain (TKD) as per local lab results.
Archival tumour tissue sample available to retrospectively confirm the HER2 status. If no archival tissue is available, this may be acceptable in exceptional cases.
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 completed more than 6 months prior to trial entry)
≥ 1 measurable lesion according to RECIST 1.1, as determined by the local site investigator assessment.
Eligible to receive treatment with the selected platinum-based doublet-chemotherapy and pembrolizumab.
Adequate organ function.
ECOG score of 0 or 1.