A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 4
- 主要终点
- Cmin of rociletinib and trametinib at steady state
研究概览
简要总结
The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib when administered in combination with trametinib.
详细描述
This is a Phase 1/2, open-label, non randomized, multicenter study evaluating the safety and efficacy of rociletinib administered in combination with trametinib.
This study will be conducted in 2 phases:
Phase 1: This will be the dose escalation phase of the study. Phase 1 will determine the MAD or MTD and RP2D of the combination of rociletinib and trametinib, and evaluate its safety and tolerability and PK profile in EGFRm NSCLC patients who have failed at least one prior EGFR TKI.
Phase 2: This will be the dose expansion phase. Phase 2 will evaluate the preliminary efficacy and pharmacodynamics of the combination of rociletinib and trametinib at the RP2D in two subsets of EGFRm NSCLC patients.
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
- •Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation
- •Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1
- •Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI
- •Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months
- •Adequate hematological and biological function; LVEF ≥50%
排除标准
- •Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification
- •Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks)
- •Known preexisting interstitial lung disease or pneumonitis
- •Concurrent use of QT-prolonging medication
- •Uncontrolled diabetes (HA1C > 10%) despite optional therapy
- •Cardiac abnormalities:
- •Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms
- •Inability to measure QT interval on ECG
- •Personal or family history of long QT syndrome
- •Implantable pacemaker or implantable cardioverter defibrillator
- •Resting bradycardia < 55 beats/min
- •Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment
- •Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy)
- •Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment
- •Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients
研究组 & 干预措施
Rociletinib and Trametinib
干预措施: Rociletinib (Drug)
Rociletinib and Trametinib
干预措施: Trametinib (Drug)
结局指标
主要结局
Cmin of rociletinib and trametinib at steady state
时间窗: Cycle 2 Day 1 to Day 2
t1/2 of rociletinib at steady state
时间窗: Cycle 2 Day 1 to Day 2
Objective Response Rate (ORR)
时间窗: Every 6 weeks until disease progression, up to approximately 24 months
ORR according to RECIST Version 1.1 as determined by Investigator assessment
AUC of rociletinib and trametinib at steady state
时间窗: Cycle 2 Day 1 to Day 2
Incidence of treatment-emergent adverse events
时间窗: Continuously, up to approximately 24 months
Treatment emergent adverse events (AEs), laboratory abnormalities and ECG abnormalities in EGFR-mutant NSCLC patients given oral rociletinib in combination with oral trametinib; defining in Phase 1 the recommended combination dose for further evaluation in Phase 2
Cmax of rociletinib and trametinib at steady state
时间窗: Cycle 2 Day 1 to Day 2
Tmax of rociletinib and trametinib at steady state
时间窗: Cycle 2 Day 1 to Day 2
次要结局
- Disease Control Rate (DCR) According to RECIST Version 1.1(Every 6 weeks until disease progression, up to approximately 24 months)
- Duration of Response (DR) According to RECIST Version 1.1(Every 6 weeks until disease progression, up to approximately 24 months)
- Progression Free Survival (PFS) According to RECIST Version 1.1(Every 6 weeks until disease progression, up to approximately 24 months)
- Cmax of rociletinib metabolites at steady state(Cycle 2 Day 1 to Day 2)
- Tmax of rociletinib metabolites at steady state(Cycle 2 Day 1 to Day 2)
- AUC of rociletinib metabolites at steady state(Cycle 2 Day 1 to Day 2)
- Cmin of rociletinib metabolites at steady state(Cycle 2 Day 1 to Day 2)
- Overall Survival (OS)(Every 12 weeks until date of death, up to approximately 60 months)
- Longitudinal changes in blood based biomarkers (i.e. mutations in EGFR) in ctDNA(Biomarker samples will be collected from each subject approximately every 3 weeks, up to approximately 24 months)