Beamion 44: A Randomized, Open-label, Multi-center Phase IIa Platform Trial to Evaluate the Safety and Tolerability of Zongertinib Plus Platinum-based Doublet Chemotherapy With or Without Pembrolizumab (and Potential Other Combinations) in Treatment-naïve Patients With Locally Advanced/Metastatic Non-squamous NSCLC With Activating HER2 Mutations
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 22
- 主要终点
- Occurrence of discontinuation and/or prolonged interruption (>7 days) of zongertinib due to treatment-related adverse events (AEs) in the first 2 cycles of treatment
研究概览
简要总结
This study is open to adults with a type of lung cancer called HER2-mutant non-squamous non-small cell lung cancer (NSCLC) that is advanced or has spread. People who have a tumor with a HER2 mutation and have not received previous treatment for their lung cancer can participate in the study. The purpose of this study is to find out how well a medicine called zongertinib is tolerated in people with this type of lung cancer, when combined with chemotherapy, with or without pembrolizumab. Zongertinib works by targeting and blocking HER2, a protein involved in cancer cell growth.
Participants are put into two groups randomly, which means by chance. One group gets zongertinib tablets combined with platinum-based chemotherapy. The other group gets the same treatment plus an additional medicine called pembrolizumab. Chemotherapy and pembrolizumab are given as an infusion into a vein. Participants take zongertinib by mouth once a day, while chemotherapy is given every 3 weeks for up to 3 months, followed by maintenance treatment for up to 2 years.
Pembrolizumab is given every 3 weeks for up to 2 years.
This study does not have a fixed duration. Participants can receive some of the study treatments for up to about 2 years and may continue to take zongertinib as long as they benefit from treatment and can tolerate it. During this time, they visit the study site regularly. Doctors regularly check the size of the tumor and whether it has spread. They also monitor participants' health and take note of any unwanted effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •Histologically or cytologically confirmed diagnosis of an advanced and/or metastatic non-squamous non-small cell lung cancer (NSCLC)
- •Documented activating human epidermal growth factor receptor 2 (HER2) mutation as per existing local lab result
- •An archival tumor tissue sample must be submitted to the central laboratory after randomization to retrospectively confirm the HER2 status
- •Patients who have not received any systemic treatment for unresectable, locally advanced or metastatic disease
- •Presence of at least one measurable non-Central Nervous System (CNS) lesion according to response evaluation criteria in solid tumors (RECIST) 1.1
- •Eligible to receive treatment with the selected platinum based doublet chemotherapy and pembrolizumab in accordance with the summary of product characteristics (SmPC)/Product Information
- •Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 Further inclusion criteria apply.
排除标准
- •Tumors with targetable alterations with approved available therapy
- •Presence or history of leptomeningeal disease
- •Radiotherapy within 4 weeks prior to treatment start with exception of palliative radiotherapy to regions other than the chest if completed at least 2 weeks prior to treatment start
- •Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening
- •Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the test drug
- •Previous therapy with a HER2-directed agent
- •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 Further exclusion criteria apply.
研究组 & 干预措施
Arm A: zongertinib + cisplatin or carboplatin and pemetrexed
干预措施: Cisplatin (Drug)
Arm B: zongertinib + cisplatin or carboplatin and pemetrexed with pembrolizumab
干预措施: Pemetrexed (Drug)
Arm B: zongertinib + cisplatin or carboplatin and pemetrexed with pembrolizumab
干预措施: Cisplatin (Drug)
Arm B: zongertinib + cisplatin or carboplatin and pemetrexed with pembrolizumab
干预措施: Carboplatin (Drug)
Arm A: zongertinib + cisplatin or carboplatin and pemetrexed
干预措施: Pemetrexed (Drug)
Arm A: zongertinib + cisplatin or carboplatin and pemetrexed
干预措施: Zongertinib (Drug)
Arm A: zongertinib + cisplatin or carboplatin and pemetrexed
干预措施: Carboplatin (Drug)
Arm B: zongertinib + cisplatin or carboplatin and pemetrexed with pembrolizumab
干预措施: Pembrolizumab (Drug)
Arm B: zongertinib + cisplatin or carboplatin and pemetrexed with pembrolizumab
干预措施: Zongertinib (Drug)
结局指标
主要结局
Occurrence of discontinuation and/or prolonged interruption (>7 days) of zongertinib due to treatment-related adverse events (AEs) in the first 2 cycles of treatment
时间窗: up to 6 weeks
次要结局
- Occurrence of serious adverse events (SAE) during the on-treatment period(up to 1.5 years)
- Occurrence of dose reduction of zongertinib(up to 1.5 years)
- Occurrence of discontinuation and/or prolonged interruption (>7 days) of zongertinib due to treatment-related AEs during the on-treatment period(up to 1.5 years)
- Occurrence of Grade ≥3 non-hematological AE during the on-treatment period(up to 1.5 years)
- Occurrence of combination limiting toxicities (CLTs) during the on-treatment period(up to 1.5 years)
- Objective response (OR) according to Response evaluation criteria in solid tumors (RECIST) 1.1 as assessed by the investigator(up to 1.5 years)
- Time to OR, defined as the time from date of randomization to first documented confirmed CR or PR among patients with OR as determined by investigator assessment per RECIST 1.1(up to 1.5 years)
- Duration of OR (DoR), defined as the time from first documented confirmed CR or PR until disease progression or death among patients with OR as determined by investigator assessment per RECIST 1.1(up to 1.5 years)
- Progression-free survival (PFS), defined as the time from randomization until tumor progression according to RECIST 1.1 as assessed by the investigator, or death from any cause, whichever occurs earlier(up to 1.5 years)
- Time on treatment (ToT), defined as the time from first dose of study treatment until zongertinib treatment discontinuation or death(up to 1.5 years)