A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 57
- 试验地点
- 125
- 主要终点
- Phase 1: Number of Participants with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to identify the recommended Phase 2 combination dose (RP2CD[s]) of the amivantamab and capmatinib combination therapy in participants with non-small cell lung cancer (NSCLC) in Phase 1 (combination dose selection), and to evaluate the antitumor effect of the amivantamab and capmatinib combination therapy in mesenchymal-epithelial transition (MET) exon 14 skipping mutation and MET amplified NSCLC, when administered at the selected RP2CD(s) in Phase 2 (expansion).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) non-small cell lung cancer (NSCLC) (any histology)
- •May have: definitively, locally treated brain metastases that are clinically stable and asymptomatic for greater than (>) 2 weeks and who are off or receiving low-dose corticosteroid treatment (less than or equal to [<=]10 milligrams (mg) prednisone or equivalent) for at least 2 weeks prior to start of study treatment
- •May have a prior malignancy (other than the disease under study) the natural history or treatment of which is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
排除标准
- •Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- •Participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets
- •Participant has symptomatic central nervous system (CNS) metastases which are neurologically unstable or have required increasing doses of steroids >10 mg prednisone or equivalent within the 2 weeks prior to study entry to manage CNS symptoms
- •Participant has uncontrolled tumor-related pain: Symptomatic lesions amenable to palliative radiotherapy (example, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior to the administration of the first study treatment
研究组 & 干预措施
Phase 1 (Combination Dose Selection)
Participants will receive capmatinib 400 milligrams (mg) orally twice daily from Cycle 1 Day 1, in combination with amivantamab 700 mg intravenous (IV) infusion (for body weight less than 80 kilograms [kg]) or 1050 mg IV infusion (for body weight greater than or equal to 80 kg) once weekly from Cycle 1 Day 1 for 4 weeks and then every 2 weeks from Week 5 (Cycle 2; each cycle of 28 days). Doses will be escalated or de-escalated based on the dose limiting toxicities (DLTs) and the recommended Phase 2 combination dose (RP2CD) will be determined by the study evaluation team (SET).
干预措施: Amivantamab (Drug)
Phase 1 (Combination Dose Selection)
Participants will receive capmatinib 400 milligrams (mg) orally twice daily from Cycle 1 Day 1, in combination with amivantamab 700 mg intravenous (IV) infusion (for body weight less than 80 kilograms [kg]) or 1050 mg IV infusion (for body weight greater than or equal to 80 kg) once weekly from Cycle 1 Day 1 for 4 weeks and then every 2 weeks from Week 5 (Cycle 2; each cycle of 28 days). Doses will be escalated or de-escalated based on the dose limiting toxicities (DLTs) and the recommended Phase 2 combination dose (RP2CD) will be determined by the study evaluation team (SET).
干预措施: Capmatinib (Drug)
Phase 2 (Dose Expansion)
Participants with mesenchymal-epithelial transition (MET) exon 14 skipping mutation who are treatment naïve (Cohort 1A), who have received prior therapy (Cohort 1B), or participants with MET amplification who have received prior therapy (Cohort 1C) will receive capmatinib in combination with amivantamab at the RP2CD determined by the SET in Phase 1.
干预措施: Capmatinib (Drug)
Phase 2 (Dose Expansion)
Participants with mesenchymal-epithelial transition (MET) exon 14 skipping mutation who are treatment naïve (Cohort 1A), who have received prior therapy (Cohort 1B), or participants with MET amplification who have received prior therapy (Cohort 1C) will receive capmatinib in combination with amivantamab at the RP2CD determined by the SET in Phase 1.
干预措施: Amivantamab (Drug)
结局指标
主要结局
Phase 1: Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (Day 1 through Day 28)
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, liver enzyme elevation, or treatment delay greater than (\>) 28 days due to unresolved toxicity.
Phase 1: Number of Participants with Adverse events (AEs) by Severity
时间窗: Up to 2 years 1 month
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Phase 2: Objective Response Rate
时间窗: Up to 2 years 1 month
ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
次要结局
- Phase 2: Disease Control Rate (DCR)(Up to 2 years 1 month)
- Phase 2: Time to Subsequent Therapy (TTST)(Up to 2 years 1 month)
- Phase 2 (Cohort 1A): Change from Baseline in Health-related Quality of Life in (HRQoL) as Assessed by European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score(Baseline up to 2 years 1 month)
- Phase 2 (Cohort 1A): HRQoL as Assessed by Patient-reported Outcomes Measurement Information System Short Form Version 2.0 - Physical Function 8c (PROMIS PF 8c) Scale Score(Up to 2 years 1 month)
- Phase 1: Number of Participants with AEs by Severity(Up to 2 years 1 month)
- Phase 1: Number of Participants with Abnormalities in Clinical Laboratory Parameters(Up to 2 years 1 month)
- Phase 2: Duration of Response (DoR)(Up to 2 years 1 month)
- Phase 2 (Cohort 1A): HRQoL as Assessed by EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale Score(Up to 2 years 1 month)
- Phase 2: Progression Free Survival (PFS)(Up to 2 years 1 month)
- Phase 2: Overall Survival (OS)(Up to 2 years 1 month)
- Phase 2 (Cohort 1A): HRQoL as Assessed by Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ) Scale Score(Up to 2 years 1 month)