A Phase 3 Study of Pembrolizumab in Combination With Carboplatin/Taxane (Paclitaxel or Nab-paclitaxel) Followed by Pembrolizumab With or Without Maintenance Olaparib in the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 851
- 试验地点
- 285
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, vs. pembrolizumab plus maintenance olaparib placebo for the treatment of squamous NSCLC. The study's 2 primary hypotheses are:
- Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to progression-free survival (PFS) per RECIST 1.1 by blinded independent clinical review (BICR).
- Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to overall survival (OS).
As of Amendment 07, there will be no further analyses for OS and patient-reported outcome assessments.
详细描述
This study has 2 phases: an Induction Phase (4 Cycles) and a Maintenance Phase (Up to 31 cycles of pembrolizumab). In the Induction Phase, participants receive pembrolizumab plus carboplatin plus a taxane (paclitaxel or nab-paclitaxel). In the Maintenance Phase, participants with a partial or complete disease response or with stable disease after completing four cycles of induction therapy and who meet eligibility criteria will be randomly assigned to receive pembrolizumab plus maintenance olaparib OR pembrolizumab plus maintenance olaparib placebo. In the Maintenance Phase, participants randomly assigned to receive pembrolizumab for up to 31 cycles plus maintenance olaparib OR maintenance olaparib placebo until centrally verified progressive disease (PD), intolerable toxicities, or physician decision.
As of Amendment 07, participants actively taking placebo will discontinue taking the placebo intervention and continue in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Have a histologically or cytologically confirmed diagnosis squamous NSCLC.
- •Have Stage IV squamous NSCLC.
- •Have measurable disease based on RECIST 1.
- •Have not received prior systemic treatment for their advanced/metastatic NSCLC.
- •Have provided archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated.
- •Note: Adequacy of biopsy specimen for the above analyses must be confirmed by the central laboratory before the participant can receive study intervention(s). Submission of another tumor specimen may be required prior to enrolling the participant, if adequate tumor tissue was not provided the first time.
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status assessed within 7 days prior to the administration of study intervention
- •Have a life expectancy of at least 3 months.
- •Has adequate organ function.
- •Male and female participants who are not pregnant and of childbearing potential must follow contraceptive guidance during the treatment period and for 180 days afterwards.
- •Male participants must refrain from donating sperm during the treatment period and for 180 days afterwards.
排除标准
- •Has non-squamous histology NSCLC.
- •Has a known additional malignancy that is progressing or has progressed within the past 3 years requiring active treatment.
- •Has known active central nervous system metastases and/or carcinomatous meningitis.
- •Has a known hypersensitivity to any components or excipients of carboplatin, paclitaxel or nab-paclitaxel, or olaparib.
- •Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
- •Has a known history of human immunodeficiency virus (HIV) infection, a known history of hepatitis B infection, or known active hepatitis C virus infection.
- •Has interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment.
- •Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor.
- •Has received prior therapy with an agent directed to programmed cell death ligand 1 (PD-L1), anti PD-L2, or directed to a stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137).
- •Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
研究组 & 干预措施
Pembrolizumab + Carboplatin + Taxane + Olaparib
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Carboplatin + Taxane + Olaparib
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Carboplatin (Drug)
Pembrolizumab + Carboplatin + Taxane + Olaparib
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Paclitaxel (Drug)
Pembrolizumab + Carboplatin + Taxane + Olaparib
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Nab-paclitaxel (Drug)
Pembrolizumab + Carboplatin + Taxane + Olaparib Placebo
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Carboplatin + Taxane + Olaparib Placebo
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Carboplatin (Drug)
Pembrolizumab + Carboplatin + Taxane + Olaparib Placebo
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Paclitaxel (Drug)
Pembrolizumab + Carboplatin + Taxane + Olaparib Placebo
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Nab-paclitaxel (Drug)
Pembrolizumab + Carboplatin + Taxane + Olaparib Placebo
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Placebo (Drug)
Pembrolizumab + Carboplatin + Taxane + Olaparib
For the Induction Phase, participants receive 4 cycles:
Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.
For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until centrally verified progressive disease, physician decision or intolerable toxicity.
干预措施: Olaparib (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to approximately 39 months
Progression-free Survival was defined as the time from the date of randomization until either documented disease progression or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, progressive disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 is presented. PFS is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase.
Overall Survival (OS)
时间窗: Up to approximately 46 months
Overall survival was the time from the date of randomization to death due to any cause. OS is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase.
次要结局
- Number of Participants With One or More Adverse Events (AEs)(Up to approximately 4 years)
- Number of Participants Who Discontinued Study Intervention Due to an AE(Up to approximately 4 years)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/ Quality of Life (QoL) (Items 29 and 30) Combined Scale Score(Baseline and Week 24)
- Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) (Items 29 and 30) Scale Score(Up to approximately 2 years)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score(Baseline and Week 24)
- Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score(Up to approximately 2 years)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score(Baseline and Week 24)
- Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score(Up to approximately 2 years)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score(Baseline and Week 24)
- Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score(Up to approximately 2 years)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score(Baseline and Week 24)
- Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score(Up to approximately 2 years)