A Randomized, Double-Blind, Phase III Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-407)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 125
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
研究概览
简要总结
In this China extension study, carboplatin and paclitaxel with or without pembrolizumab (MK-3475, KEYTRUDA®) will be administered to Chinese adults with first line metastatic squamous non-small cell lung cancer (NSCLC).
The primary hypotheses are that treatment with pembrolizumab prolongs: 1) Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by a blinded central imaging vendor compared to placebo, and 2) Overall Survival (OS) in Chinese participants.
After analysis of interim results was conducted, the protocol was amended (Amendment 5) to allow participants the option to discontinue placebo in the control arm and to switch to pembrolizumab in the event of documented progressive disease as assessed by central review.
详细描述
The MK-3475-407-China Extension Study enrolled a total of 125 participants, of which 15 participants have been also previously enrolled in the MK-3475-407 global study (NCT02775435). This China extension study did not include nano particle albumin-bound paclitaxel (nab-paclitaxel) that was an option in the global base study, because nab-paclitaxel it is not yet approved for treatment of NSCLC in China.
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
- •Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-American Joint Committee on Cancer [AJCC]) squamous NSCLC.
- •Has measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
- •Has not received prior systemic treatment for metastatic NSCLC.
- •Has provided tumor tissue from locations not radiated prior to biopsy.
- •Has a life expectancy of at least 3 months.
- •Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
- •Has adequate organ function.
- •If female of childbearing potential, is willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of study treatment.
- •If male with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception starting with the first dose of study treatment through 95 days after the last dose of study treatment. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
排除标准
- •Has non-squamous histology NSCLC.
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab.
- •Before the first dose of study drug: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease; b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease; c) Has had major surgery (<3 weeks prior to first dose).
- •Received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment.
- •Completed palliative radiotherapy within 7 days of the first dose of study treatment.
- •Is expected to require any other form of antineoplastic therapy while on study.
- •Has received a live-virus vaccination within 30 days of planned treatment start.
- •Has a known history of prior malignancy except if the participant 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 pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) Version 4 criteria.
- •Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
- •Has a known sensitivity to any component of carboplatin or paclitaxel or nab-paclitaxel.
- •Has active autoimmune disease that has required systemic treatment in past 2 years.
- •Is on chronic systemic steroids.
- •Had prior treatment with any other anti-programmed cell death 1 (anti-PD-1), or programmed cell death ligand 1 (PD-L1) or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms.
- •Has participated in any other pembrolizumab trial and has been treated with pembrolizumab.
- •Has an active infection requiring therapy.
- •Has known history of Human Immunodeficiency Virus (HIV).
- •Has known active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection.
- •Is, at the time of providing documented informed consent, a regular user (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol).
- •Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
研究组 & 干预措施
Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) PLUS carboplatin Area Under the Curve (AUC) 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) PLUS carboplatin Area Under the Curve (AUC) 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
干预措施: Paclitaxel (Drug)
Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) PLUS carboplatin Area Under the Curve (AUC) 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
干预措施: Carboplatin (Drug)
Chemotherapy
Participants receive normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
干预措施: Paclitaxel (Drug)
Chemotherapy
Participants receive normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
干预措施: Carboplatin (Drug)
Chemotherapy
Participants receive normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
干预措施: Saline placebo for pembrolizumab (Drug)
结局指标
主要结局
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
时间窗: Up to approximately 33 months
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), 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 also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 is presented. Data are from the product-limit (Kaplan-Meier) method for censored data.
Overall Survival (OS)
时间窗: Up to approximately 39 months
OS was defined as the time from randomization to death due to any cause. OS is presented. Data are from the product-limit (Kaplan-Meier) method for censored data.
次要结局
- Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 33 months)
- Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 30 months)
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 31 months)
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)(Up to approximately 29 months)