A Randomized Open-Label Phase III Trial of Pembrolizumab Versus Platinum Based Chemotherapy in 1L Subjects With PD-L1 Strong Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 305
- 主要终点
- Progression Free Survival (PFS) Rate at Month 6
研究概览
简要总结
This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies in the treatment of participants with previously untreated stage IV, programmed cell death ligand 1 (PD-L1) strong expressing Non-Small Cell Lung Cancer (NSCLC). The primary hypothesis of this study is that participants with PD-L1 strong NSCLC will have a longer Progression Free Survival (PFS), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) when treated with pembrolizumab than when treated with SOC platinum-based chemotherapies.
With Amendment 09 (20 December 2017), once participants have achieved the study objective or the study has ended, participants will be discontinued from this study and enrolled in an extension study to continue protocol-defined assessments and treatment.
详细描述
Treatment Phase: Participants randomized to pembrolizumab will be treated for up to 35 cycles or until documented progressive disease (PD) occurs. Participants randomized to SOC chemotherapies will be treated with their randomized study drug for up to 4-6 cycles. After this, participants with non-squamous histologies may choose to be treated with maintenance pemetrexed for the remainder of the study or until disease progression, unacceptable adverse event(s) (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the participant, noncompliance with study treatment or procedures requirements, the participant receives 35 treatments of study treatment (pembrolizumab arm only), or administrative reasons. Participants receiving pembrolizumab who stop drug administration after receiving 35 study treatments for reasons other than disease progression or intolerability, or participants who attain a complete response and stop study treatment may be eligible for retreatment with pembrolizumab upon experiencing disease progression. The decision to retreat with a second course of pembrolizumab will be at the discretion of the Investigator only if participants meet the criteria for retreatment and the study is ongoing. Retreatment (second course) is limited to 17 cycles. Participants randomized to receive SOC chemotherapy may be eligible to receive pembrolizumab if criteria to switch are met.
Switch-Over Phase: This is only applicable for participants randomized to receive SOC. Eligible participants will be treated with pembrolizumab for the remainder of the study or until disease progression, unacceptable AEs, intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the participant, noncompliance with study treatment or procedures requirements, the participant receives 35 treatments of study treatment (pembrolizumab arm only), or administrative reasons.
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
- 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
- •Histological or cytological diagnosis of Stage IV NSCLC lacking epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation, and received no prior systemic chemotherapy treatment for their metastatic NSCLC
- •At least one radiographically measurable lesion per RECIST 1.1
- •Life expectancy of at least 3 months
- •Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
- •Adequate organ function
- •No history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
- •Provided newly obtained formalin fixed tumor tissue from a biopsy of a tumor at the time of or AFTER the diagnosis of metastatic disease has been made AND from a site not previously irradiated
- •PD-L1 strong expressing tumor as determined by immunohistochemistry (IHC) at a central laboratory
- •Female participants must have a negative pregnancy test at screening if of childbearing potential or be of non-childbearing potential
- •Female participants of childbearing potential and male partners with female partners of childbearing potential must agree to use 2 adequate barrier methods of contraception during the study and for 120 days after last dose of study drug and up to 180 days after last dose of chemotherapy
排除标准
- •EGFR sensitizing mutation and/or ALK translocation
- •Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
- •Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of study drug
- •Tumor specimen is not evaluable for PD-L1 expression by the central laboratory
- •Receiving systemic steroid therapy < 3 days prior to first dose of study drug or receiving any other form of immunosuppressive medication
- •Expected to require any other form of systemic or localized antineoplastic therapy during the study
- •Received prior systemic cytotoxic chemotherapy, biological therapy, major surgery within 3 weeks of first dose of study drug; received thoracic radiation therapy of > 30 gray (Gy) within 6 months of first dose of study drug
- •Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- •Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •Allogenic tissue/solid organ transplant
- •Interstitial lung disease or pneumonitis that has required oral or IV steroids
- •Received or will receive a live vaccine within 30 days prior to first dose of study drug
- •Active infection requiring IV systemic therapy
- •Known history of human immunodeficiency virus (HIV)
- •Known active tuberculosis, or hepatitis B or C
- •Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- •Is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
- •Pregnant or breastfeeding, or expecting to conceive or father children during the study and through 120 days after last dose of pembrolizumab or 180 days after last dose of SOC chemotherapy
- •Immediate family member who is investigational site or sponsor staff directly involved with this study
研究组 & 干预措施
Pembrolizumab
Participants receive pembrolizumab 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles.
干预措施: Pembrolizumab (Drug)
Paclitaxel+Carboplatin
Participants receive paclitaxel 200 mg/m^2 and carboplatin Area Under the Curve (AUC) 5 or 6, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 every three weeks (Q3W) maintenance for participants with non-squamous histologies for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Paclitaxel (Drug)
Paclitaxel+Carboplatin
Participants receive paclitaxel 200 mg/m^2 and carboplatin Area Under the Curve (AUC) 5 or 6, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 every three weeks (Q3W) maintenance for participants with non-squamous histologies for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Carboplatin (Drug)
Paclitaxel+Carboplatin
Participants receive paclitaxel 200 mg/m^2 and carboplatin Area Under the Curve (AUC) 5 or 6, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 every three weeks (Q3W) maintenance for participants with non-squamous histologies for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Pemetrexed (Drug)
Pemetrexed+Carboplatin
Participants receive pemetrexed 500 mg/m^2 and carboplatin AUC 5 or 6, IV infusion on Day 1 of each 21-day cycle for 4-6 cycles; participants with non-squamous histologies may then receive pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle as maintenance therapy for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Carboplatin (Drug)
Pemetrexed+Carboplatin
Participants receive pemetrexed 500 mg/m^2 and carboplatin AUC 5 or 6, IV infusion on Day 1 of each 21-day cycle for 4-6 cycles; participants with non-squamous histologies may then receive pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle as maintenance therapy for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Pemetrexed (Drug)
Pemetrexed+Cisplatin
Participants receive pemetrexed 500 mg/m^2 and cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 Q3W maintenance for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Pemetrexed (Drug)
Pemetrexed+Cisplatin
Participants receive pemetrexed 500 mg/m^2 and cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 Q3W maintenance for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Cisplatin (Drug)
Gemcitabine+Carboplatin
Participants receive gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and carboplatin AUC 5 or 6, administered as IV infusion on Day 1 of a 21-day cycle, for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Carboplatin (Drug)
Gemcitabine+Carboplatin
Participants receive gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and carboplatin AUC 5 or 6, administered as IV infusion on Day 1 of a 21-day cycle, for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Gemcitabine (Drug)
Gemcitabine+Cisplatin
Participants receive gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Cisplatin (Drug)
Gemcitabine+Cisplatin
Participants receive gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Rate at Month 6
时间窗: Month 6
PFS was defined as the time from randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first and was based on blinded independent central radiologists' (BICR) review. Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. (Note: the appearance of one or more new lesions was also considered progression). Participants were evaluated every 9 weeks with radiographic imaging to assess their response to treatment. The data cutoff was 09-May-2016. The PFS rate at Month 6 was calculated.
次要结局
- Overall Survival (OS) Rate(12 months)
- Objective Response Rate (ORR)(Up to ~1.6 years)