An Open-label, Phase I, Dose Escalation, Expansion Study of MGY825 in Adult Patients With Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 23
- 主要终点
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
Study of MGY825 single agent in adult patients with advanced non-small cell lung cancer.
详细描述
First in human, phase I, multicenter, open-label study of MGY825 single agent with a dose escalation and a dose expansion in adult patients with advanced non-small cell lung cancer (NSCLC).
The dose escalation part investigated the safety and tolerability of MGY825 in adult patients with advanced NSCLC harboring NFE2L2, or KEAP1 or CUL3 (NFE2L2/KEAP1/CUL3) mutations. Patient enrollment was based on locally available test results of mutation status.
An exploratory assessment on the effect of food could be investigated during the dose escalation part.
The dose expansion part assessed the preliminary anti-tumor activity and further assess the safety and tolerability of MGY825 in adult patients with advanced NSCLC divided in two patient groups.
Group 1: Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation in the study.
- •Dose escalation and dose expansion group 1:
- •Patients with histologically or cytologically confirmed diagnosis of advanced (metastatic or unresectable) NFE2L2/KEAP1/CUL3 mutant NSCLC. Local data confirming the NFE2L2/KEAP1/CUL3 mutation status in tissue must be available for enrollment.
- •Dose expansion group 2:
- •Patients with histologically or cytologically confirmed diagnosis of advanced (metastatic or unresectable) NSCLC irrespective of NFE2L2/KEAP1/CUL3 mutation status.
- •All patients:
- •Patients must have progressed after 1 platinum-based chemotherapy regimen and PD-(L)1 antibody therapy either sequentially or concurrent with chemotherapy, where indicated, for Stage IV NSCLC.
- •Patients treated with neo-adjuvant / adjuvant platinum-based therapy that progressed within 6 months of treatment are permitted to participate.
- •Prior therapy with VEGF/VEGFR targeting agents is permitted. Prior treatment with approved targeted drugs (e.g., EGFRi, ALKi, METi) is mandatory in patients with NSCLC whose tumor bears actionable mutations.
- •Presence of at least one measurable lesion according to RECIST v1.
- •Patient must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening and during study treatment. A recent biopsy collected after the last systemic treatment and within 3 months before study entry may be submitted at screening.
排除标准
- •Having out of range laboratory values defined as:
- •Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 60 mL/min Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN ALT > 3 x ULN AST > 3 x ULN ANC < 1.0 x 109/L Platelet count < 75 x 109/L Hemoglobin < 9 g/dL
- •Impaired cardiac function or clinically significant cardiac disease, including any of the following:
- •Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade ≥2), uncontrolled hypertension or clinically significant arrhythmia.
- •QTcF > 470 msec on screening ECG or congenital long QT syndrome. Acute myocardial infarction or unstable angina pectoris < 3 months prior to study entry.
- •Presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery) or increasing doses of corticosteroids within 2 weeks prior to study entry. Patients with treated symptomatic brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to study entry) and at a dose of ≤ 10 mg per day prednisone or equivalent for at least 2 weeks before administration of any study treatment.
- •Known active COVID-19 infection.
- •Unable or unwilling to swallow capsules as per dosing schedule. Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Dose escalation
Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status
干预措施: MGY825 (Drug)
Dose expansion group 1
Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status
干预措施: MGY825 (Drug)
Dose expansion group 2
Patients with advanced NSCLC irrespective of prior knowledge of NFE2L2/KEAP1/CUL3 mutational status.
干预措施: MGY825 (Drug)
结局指标
主要结局
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 28 months
Assessment of safety of study drug as a single agent
Frequency of dose interruptions and reductions
时间窗: 28 months
Assessment of tolerability of study drug as a single agent
Dose intensity
时间窗: 28 months
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure.
Incidence and nature of dose limiting toxicities (DLTs) during the first 28 days of treatment with the study drug
时间窗: 28 days
A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 assessed as not primarily related to disease, disease progression, inter-current illness or concomitant medications that occurs during the first 28 days of treatment with the study drug. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
次要结局
- Area under the concentration-time curve (AUC)(20 months)
- Peak concentration (Cmax)(20 months)
- Overall response rate (ORR) per RECIST 1.1(28 months)
- Time to reach maximum drug concentrations in systemic circulation (Tmax)(20 months)
- Progression free survival (PFS) per RECIST 1.1(28 months)
- Duration of response (DOR) per RECIST 1.1(28 months)