A Phase 1b With Expansion Study Evaluating the Efficacy and Safety of Momelotinib Combined With Trametinib in Subjects With Metastatic KRAS-mutated Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Platinum-Based Chemotherapy Preceded by a Dose-finding Lead-in Phase
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 21
- 主要终点
- For the Dose-finding Lead-in Phase, incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
This study is conducted in two phases. The Dose-finding Lead-in Phase, Part A, will evaluate the safety and determine the maximum tolerated dose (MTD) of momelotinib (MMB) when combined with trametinib. Once the MTD of momelotinib (MMB) is determined, the study will proceed to the Dose-finding Lead-in Phase, Part B, to determine the MTD of trametinib. After the MTD is established, the study may proceed to an expansion phase to determine the efficacy, safety, and tolerability of MMB combined with trametinib at the MTD in participants with kirsten rat sarcoma viral oncogene homolog (KRAS) mutated metastatic non-small cell lung cancer (NSCLC). Each treatment cycle will consist of 28 days and treatment will continue in the absence of disease progression, unacceptable toxicity, consent withdrawal, or participant's refusal of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Individuals with KRAS-mutated metastatic or recurrent non-small cell lung cancer
- •Radiologic documentation of disease progression
- •Measurable disease per RECIST v1.1
- •Adequate organ function defined as follows:
- •Hepatic: Total conjugated bilirubin ≤ 1.25 x upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limit of normal (ULN) or < 5 x ULN in the setting of liver metastases
- •Hematological: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelet ≥ 100 x 10^9/L, hemoglobin ≥ 9 g/dL
- •Renal: Serum creatinine < 1.5 x ULN OR calculated creatinine clearance (CLcr) ≥ 60 ml/min
- •Adequate left ventricular ejection fraction (LVEF) ≥ 50%
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Negative serum pregnancy test for females
排除标准
- •Less than or equal to 3 weeks since receiving treatment with biologic, small molecule, chemotherapy or other agent for non-small cell lung cancer and 28 days since any prior immunotherapy (such as nivolumab)
- •History of a concurrent or second malignancy, except for specified exceptions in the protocol or any other cancer that has been in complete remission for ≥ 5 years
- •Known positive status for human immunodeficiency virus (HIV)
- •Chronic active or acute viral hepatitis A, B, or C infection or hepatitis B or C carrier
- •Presence of ≥ Grade 2 peripheral neuropathy
- •Brain metastases, or spinal cord compression. Individuals with brain metastases are allowed if they have been treated with irradiation or surgery, are clinically stable without steroid treatment. Individuals with documented leptomeningeal disease are not eligible
- •A history of uveitis and/or scleritis
- •Retinal pathology beyond normal age-related processes
- •Evidence of a retinal vein occlusion on ophthalmological exam or a history of retinal vein occlusion
- •History of newly diagnosed or uncontrolled glaucoma/intraocular pressure > 21 mm Hg as measured by tonography
- •Use of daily and/or chronic oral or ocular steroids. Individuals must be off daily steroids for at least 3 weeks prior to enrolling into the trial
- •History of interstitial pneumonitis
- •History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 480 ms for males and females)
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Momelotinib (MMB) dose escalation
Participants will receive momelotinib (MMB) plus trametinib. Momelotinib (MMB) dose will increase to find the MTD.
干预措施: Momelotinib (MMB) (Drug)
Momelotinib (MMB) dose escalation
Participants will receive momelotinib (MMB) plus trametinib. Momelotinib (MMB) dose will increase to find the MTD.
干预措施: Trametinib (Drug)
Trametinib dose escalation
Participants will receive momelotinib (MMB) plus trametinib. Trametinib dose will increase to find the MTD.
干预措施: Momelotinib (MMB) (Drug)
Trametinib dose escalation
Participants will receive momelotinib (MMB) plus trametinib. Trametinib dose will increase to find the MTD.
干预措施: Trametinib (Drug)
Momelotinib (MMB)+trametinib
Expansion Phase: participants will receive momelotinib (MMB) plus trametinib for the duration of the study.
干预措施: Momelotinib (MMB) (Drug)
Momelotinib (MMB)+trametinib
Expansion Phase: participants will receive momelotinib (MMB) plus trametinib for the duration of the study.
干预措施: Trametinib (Drug)
结局指标
主要结局
For the Dose-finding Lead-in Phase, incidence of dose limiting toxicities (DLTs)
时间窗: Up to 28 days
Dose limiting toxicities (DLTs) refer to toxicities experienced during the first 28 days of treatment that have been judged to be clinically significant and at least possibly related to study treatment.
For Expansion Phase, disease control rate (DCR) at Week 8
时间窗: Week 8
Disease control rate (DCR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumor (RECIST) v1.1.
次要结局
- For the Dose-finding Lead-in Phase, disease control rate (DCR) at Week 8(Week 8)
- For the Dose-finding Lead-in Phase, overall survival(Up to 2 years)
- For the Dose-finding Lead-in Phase, progression free survival (PFS)(Up to 2 years)
- For the Dose-finding Lead-in Phase, overall response rate (ORR)(Up to 2 years)
- For Expansion Phase, overall response rate (ORR)(Up to 2 years)
- For the Dose-finding Lead-in Phase, plasma pharmacokinetics (PK) parameters of momelotinib (MMB) and major metabolite GS-644603 as measured by Cmax and AUCtau(Days 1 and 15 (Cycle 1 only))
- For Expansion Phase, progression free survival (PFS)(Up to 2 years)
- For Expansion Phase, overall survival(Up to 2 years)