A Phase 2, Multicenter, Randomized Study to Compare the Efficacy and Safety of MK-7684A or MK-7684A Plus Docetaxel Versus Docetaxel Monotherapy in the Treatment of Participants With Metastatic Non-small Cell Lung Cancer With Progressive Disease After Treatment With a Platinum Doublet Chemotherapy and Immunotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 255
- 试验地点
- 95
- 主要终点
- Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment
研究概览
简要总结
The main purpose of this study is to compare pembrolizumab/vibostolimab coformulation (MK-7684A) plus docetaxel or pembrolizumab/vibostolimab coformulation to normal saline placebo plus docetaxel. Participants with metastatic non-small cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and treatment with one prior anti- programmed cell death 1 (PD-1)/ programmed cell death ligand 1(PD-L1) monoclonal antibody (mAb). MK-7684A is a coformulation product of pembrolizumab/vibostolimab. The dual primary hypotheses of the study are pembrolizumab/vibostolimab coformulation plus docetaxel and pembrolizumab/vibostolimab coformulation is superior to normal saline placebo plus docetaxel with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
详细描述
Participants may receive additional 17 cycles of pembrolizumab/vibostolimab (each cycle length = 21 days) for an additional 1 year of treatment as second course phase at investigator's discretion.
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
- Double (Participant, Investigator)
盲法说明
Arm 1 and Arm 3: Double-blind with in-house blinding Arm 2: Unblinded Open-label
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 metastatic non-small cell lung cancer (NSCLC)
- •Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or reactive oxygen species (ROS) 1 directed therapy is not indicated as primary therapy
- •Has progressive disease (PD) on treatment with one prior anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies
- •Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment
- •Has PD as determined by the investigator after platinum doublet chemotherapy for metastatic disease
- •Has measurable disease defined as at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI), based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
- •Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- •Has a life expectancy of at least 3 months
- •Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days prior to randomization
- •Male participants randomized to docetaxel are eligible to participant if they agree to refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse; or 2) must agree to follow contraceptive guidance as per study protocol unless confirmed to be azoospermic during the intervention period and for at least 180 days after the last dose of docetaxel
- •Female participants must be not pregnant, not breastfeeding, and not be a woman of child-bearing potential (WOCBP). A WOCBP is eligible is she agrees to either use contraception, or be abstinent from heterosexual intercourse during the intervention period and for ≥120 days after the last dose of study intervention. If a WOCBP is randomized to docetaxel, she agrees not to donate eggs and either uses contraception or be abstinent from heterosexual intercourse during the treatment period and for ≥180 days after the last dose of docetaxel
- •Has adequate organ function
排除标准
- •Has known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy
- •Has received docetaxel as monotherapy or in combination with other therapies
- •Has received previous treatment with another agent targeting the T-cell immunoreceptor with immunoglobulin [Ig] and immunoreceptor tyrosine-based inhibitory motif [ITIM] domains (TIGIT) pathway
- •Has received radiotherapy within 2 weeks of start of study intervention. One week washout is permitted for palliative radiation to non-CNS disease
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
- •Has severe hypersensitivity (≥Grade 3) to docetaxel or pembrolizumab/vibostolimab coformulation 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 or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention
- •Has interstitial lung disease, or history of pneumonitis requiring steroids for treatment
- •Has known history of active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
- •Has had an allogenic tissue/solid organ transplant
- •Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
研究组 & 干预措施
Arm 1: Pembrolizumab/Vibostolimab coformulation + Docetaxel
Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years plus docetaxel 75 mg/m^2 via IV infusion Q3W. Each cycle will be 21 days.
干预措施: Pembrolizumab/Vibostolimab coformulation (Biological)
Arm 1: Pembrolizumab/Vibostolimab coformulation + Docetaxel
Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years plus docetaxel 75 mg/m^2 via IV infusion Q3W. Each cycle will be 21 days.
干预措施: Docetaxel (Drug)
Arm 2: Pembrolizumab/Vibostolimab coformulation
Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion Q3W for up to 35 cycles up to approximately 2 years. Each cycle will be 21 days.
干预措施: Pembrolizumab/Vibostolimab coformulation (Biological)
Arm 3: Placebo + Docetaxel
Participants receive normal saline placebo via IV infusion Q3W for up to 35 cycles up to approximately 2 years plus docetaxel 75 mg/m^2 IV infusion Q3W. Each cycle will be 21 days.
干预措施: Docetaxel (Drug)
Arm 3: Placebo + Docetaxel
Participants receive normal saline placebo via IV infusion Q3W for up to 35 cycles up to approximately 2 years plus docetaxel 75 mg/m^2 IV infusion Q3W. Each cycle will be 21 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment
时间窗: Up to approximately 21 months
PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR is presented.
次要结局
- Objective Response Rate (ORR) Per RECIST 1.1 by BICR Assessment(Up to approximately 21 months)
- Overall Survival (OS)(Up to approximately 21 months)
- Duration of Response (DOR) Per RECIST 1.1 by BICR Assessment(Up to approximately 21 months)
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 27 months)
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 39 months)