A Phase I/II Multi-site Study of Rucaparib and Pembrolizumab Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer After Initial Therapy With Carboplatin, Pemetrexed, and Pembrolizumab
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 3
- 主要终点
- Median Duration of Time From Start of Treatment to Time of Progression
研究概览
简要总结
This study is a multi-center, Phase I/II, single arm trial to assess the safety and efficacy of the combination of oral rucaparib plus intravenous pembrolizumab as maintenance therapy in patients with stage IV non-squamous non-small cell lung cancer (NSCLC) without progressive disease (PD), as confirmed on CT scans, after induction therapy with carboplatin/pemetrexed/pembrolizumab (CPP) triplet therapy.
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
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be ≥18 years of age on day of signing informed consent.
- •Have a life expectancy of at least 3 months.
- •Have a diagnosis of stage IV non-squamous NSCLC whose tumors do not have an epidermal sensitizing growth factor (EGFR) mutation or BRAF mutation or rearrangements in ALK (anaplastic lymphoma kinase) or ROS-1 and have at least one measurable lesion based on RECIST v1.
- •Have a performance status of 0 or 1 on the ECOG Performance Scale (Appendix 15.1).
- •Demonstrate adequate organ function
- •Female subject of childbearing potential should have a serum pregnancy test within -28 days of enrollment and 72 hours prior to receiving the first dose of study medications.
- •Female subjects of childbearing potential must be willing to use a highly effective method of contraception as outlined in Section 6.3.3 for the course of the study through 180 days after the last dose of study medications. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- •Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 6.3.3, starting with the first dose of study therapy through 180 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- •If the patient has archival tissue, this should be collected for correlative studies. If archival tissue does not exist, a new biopsy is not required
排除标准
- •Received previous systemic therapy for stage IV NSCLC
- •Received radiation to the lungs >30Gy ≤6 months of enrollment
- •Received palliative radiation within 7 days of enrollment
- •Had prior treatment with any other anti-PD-1, PD-L1, or PD-L2 agent or an antibody targeting other immune-regulatory receptors or mechanisms
- •Received prior treatment with a PARP inhibitor
- •Has a known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has active autoimmune disease that has required systemic treatment within the past 2 years
- •Subjects requiring daily corticosteroids >10mg of prednisone (or its equivalent) would be excluded from the study.
- •Has evidence of interstitial lung disease or a history of non-infectious pneumonitis that required oral or intravenous glucocorticoids to assist with management
- •Has an active infection requiring systemic therapy
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment
- •Has a diagnosis of immunodeficiency (including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency (AIDS)-related illness) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment
- •Has a known history of active TB (Bacillus Tuberculosis)
- •Has known active Hepatitis B or Hepatitis C
- •Has received a live vaccine within 30 days of enrollment
- •A medical condition that requires daily systemic corticosteroids, greater than the equivalent of 10mg of prednisone
研究组 & 干预措施
Rucaparib and Pembrolizumab Maintenance
All patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days).
This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle).
干预措施: Pembrolizumab (Drug)
Rucaparib and Pembrolizumab Maintenance
All patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days).
This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle).
干预措施: Pemetrexed (Drug)
Rucaparib and Pembrolizumab Maintenance
All patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days).
This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle).
干预措施: Carboplatin (Drug)
Rucaparib and Pembrolizumab Maintenance
All patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days).
This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle).
干预措施: Rucaparib (Drug)
结局指标
主要结局
Median Duration of Time From Start of Treatment to Time of Progression
时间窗: Up to 5 years
The primary endpoint is median progression free survival (PFS) which is defined as the median duration of time from the start of treatment to progression. Progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.
次要结局
- Median Duration of Time From the Start of Treatment Until Death(Up to 5 years)
- Response Rate(Up to 5 years)