A Phase 1b Study of Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naïve Metastatic Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 主要终点
- Incidence of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This study will evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) of momelotinib (MMB) and erlotinib, as well as define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with erlotinib in adults with epidermal growth factor receptor (EGFR)-mutated, EGFR tyrosine kinase inhibitor (TKI) naive metastatic non-small cell lung cancer (NSCLC). Participants will be sequentially enrolled to receive progressively increasing doses of momelotinib (MMB) in combination with erlotinib. Escalation of momelotinib (MMB) doses will proceed to the MTD, defined as the highest tested dose associated with dose-limiting toxicities (DLT) during the first 28 days of combined erlotinib and momelotinib (MMB) treatment. There will be four dose levels and each treatment cycle will consist of 28 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Metastatic NSCLC with documented EGFR exon 19 deletion or exon 21 (L858R) substitution mutation
- •Treatment naive OR one prior standard chemotherapy that is platinum-based
- •Adequate organ function defined as follows:
- •Hepatic: Total bilirubin < upper limit of the normal range (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
- •Hematological: absolute neutrophil count (ANC) ≥1500 cells/mm^3, platelet ≥ 100,000 cells/mm^3, hemoglobin ≥ 9.0 g/dL
- •Renal: Serum creatinine < ULN OR calculated creatinine clearance (CLcr) of ≥ 60 ml/min
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
排除标准
- •Known positive status for human immunodeficiency virus (HIV)
- •Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C)
- •Presence of > Grade 1 peripheral neuropathy
- •Symptomatic leptomeningeal, brain metastases, or spinal cord compression.
- •History of interstitial pneumonitis
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Momelotinib (MMB)+erlotinib
Participants will receive momelotinib (MMB) plus erlotinib.
干预措施: Momelotinib (MMB) (Drug)
Momelotinib (MMB)+erlotinib
Participants will receive momelotinib (MMB) plus erlotinib.
干预措施: Erlotinib (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLTs)
时间窗: Up to 28 days
Dose limiting toxicities refer to toxicities experienced during the first 28 days of combined erlotinib and momelotinib (MMB) treatment that have been judged to be clinically significant and related to study treatment.
Safety as Assessed by the Incidence of Adverse Events (AEs)
时间窗: Up to 2 years plus 30 days
Safety as Assessed by the Percentage of Participants Experiencing Treatment-Emergent Graded Lab Abnormalities (including Chemistry, Coagulation, Hematology, and Urinalysis)
时间窗: Up to 2 years plus 30 days
Change from Baseline in Vital Signs
时间窗: Up to 2 years
次要结局
- Overall Response Rate(Until disease progression (up to 2 years))
- Overall Survival(Until disease progression (up to 2 years))
- Progression-Free Survival(Until disease progression (up to 2 years))
- Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB)(Predose and up to 24 hours postdose)
- PK Parameter: AUCtau of momelotinib (MMB)(Predose and up to 24 hours postdose)
- PK Parameter: Cmax of Erlotinib(Predose and up to 24 hours postdose)
- PK Parameter: AUCtau of Erlotinib(Predose and up to 24 hours postdose)