A Phase II Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy for Metastatic Triple-Negative Breast Cancer (mTNBC) - (KEYNOTE-086)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 254
- 主要终点
- Number of Participants Who Experienced at Least One Adverse Event (AE)
研究概览
简要总结
This is a two-part study of pembrolizumab monotherapy in participants with metastatic triple-negative breast cancer (mTNBC). Part 1 of the study will examine the efficacy and safety of pembrolizumab monotherapy as first line or above treatment in participants who have received either no prior systemic treatment or at least one prior systemic treatment for metastatic breast cancer. Part 2 of the study, if done, will expand the investigation of pembrolizumab treatment in a subgroup of participants from Part 1 and will only start after enrollment in Part 1 has been completed. There will be no hypothesis testing in this study.
详细描述
Qualified participants who complete up to ~2 years of pembrolizumab treatment but progress after discontinuation may be eligible for a second course of pembrolizumab for up to ~1 additional year, at the Investigator's discretion. Per protocol, response or progression during this second course will not count towards efficacy outcome measure and adverse events during this second course will not count towards safety outcome measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •For the purposes of this study, neoadjuvant and/or adjuvant chemotherapy regimens do not count as a prior line of therapy.
- •For second line plus monotherapy (Parts 1 and 2):
- •Has received at least one systemic treatment for metastatic breast cancer
- •Has documented disease progression on or after the most recent therapy
- •Prior treatment must include an anthracycline and a taxane in the neoadjuvant, adjuvant, or metastatic setting
- •For first line monotherapy (Part 1):
- •Has received no prior systemic treatment for metastatic breast cancer
- •Has PD-L1-positive mTNBC.
- •For second line plus monotherapy (Part 2):
- •Has PD-L1 strong positive mTNBC
- •For all parts:
- •Has mTNBC confirmed by a central laboratory
- •For biomarker analysis, adequate newly obtained core or excisional biopsy of a not-previously-irradiated metastatic tumor lesion (mandatory)
- •Has measurable metastatic disease
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
- •Male participants should agree to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment
- •Has adequate organ function
排除标准
- •Is currently participating and receiving study treatment, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to study Day 1
- •Has received prior anti-cancer monoclonal antibody (mAb) therapy for direct anti-neoplastic treatment within 4 weeks prior to study Day 1
- •Has received prior chemotherapy, targeted small molecule therapy, or radiation therapy within at least 2 weeks prior to study Day 1
- •Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered within at least 2 weeks prior to study Day 1
- •Has an active autoimmune disease requiring systemic treatment in past 2 years
- •Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
- •Has known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
- •Has radiographically-detectable central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis or a history of interstitial lung disease
- •Has an active infection requiring systemic therapy
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- •Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
- •Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137) or has participated in Merck MK-3475 (pembrolizumab) study
- •Has a known history of human immunodeficiency virus (HIV)
- •Has known active Hepatitis B or C
- •Has received a live vaccine within 30 days of planned start of study treatment
结局指标
主要结局
Number of Participants Who Experienced at Least One Adverse Event (AE)
时间窗: Up to ~31 months
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who experienced at least one AE, for the first pembrolizumab course, was assessed from enrollment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug.
ORR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With Programmed Cell Death- Ligand 1 (PD-L1) Positive Tumor Expression
时间窗: Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for the subgroup of Cohort A participants with tumor immunohistochemistry (IHC) defined-PD-L1 positive expression (PD-L1+). Per protocol final ORR analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Central Imaging Vendor (CIV) in All Cohort A Participants
时间窗: Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in sum of diameters \[SOD\] of target lesions) per RECIST 1.1 by CIV. ORR was estimated by Agresti-Coull (A-C) method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort, for all participants in Cohort A. Per protocol final ORR analysis in all Cohort A participants was done at the time of final statistical efficacy analysis, with a 10-November (Nov)-2017 cutoff. Per protocol ORR per RECIST 1.1 by CIV in all Cohort A participants was planned and conducted as a pre-specified primary outcome analysis. Per protocol ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record.
Number of Participants Who Discontinued Study Drug Due to an AE
时间窗: Up to ~31 months
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who discontinued study drug due to an AE, in the first pembrolizumab course, was assessed from enrolment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug.
次要结局
- ORR Per RECIST 1.1 by CIV in All Cohort B Participants(Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017))
- Duration of Response (DOR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants(Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017))
- Overall Survival (OS) in All Cohort A and Cohort B Participants(Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017))
- DCR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression(Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017))
- Progression Free Survival (PFS) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants(Up to ~28 months (through pre-specified final statistical analysis cut-off date of 10-Nov-2017))
- Odds Ratio of Association Between PD-L1 Tumor Expression and Objective Response (OR) Per RECIST 1.1 by CIV in Cohort A Participants(Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017))
- OS in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression(Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017))
- DOR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression(Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017))
- Disease Control Rate (DCR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants(Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017))
- PFS Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression(Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017))