A Phase Ib Study of Pembrolizumab (MK-3475) in Chinese Subjects With Locally Advanced or Metastatic Melanoma (Keynote-151)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 103
- 主要终点
- Number of Participants Who Discontinued Study Treatment Due to an AE
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability, and objective response rate (ORR) of pembrolizumab (MK-3475) in Chinese participants with locally advanced or metastatic melanoma, with disease progression following first line chemotherapy or targeted therapy. ORR will be based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
With Amendment 6 (effective date 18-Mar-2022), once the study objectives have been met or the study has ended, participants will be discontinued from this study and may be enrolled in an extension study to continue protocol-defined assessments and treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Is of the Chinese descent, was born in China, and has a Chinese home address.
- •Has histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy.
- •Participant may not have a diagnosis of uveal or ocular melanoma.
- •Overall proportion of participants with mucosa melanoma will be no more than 22%.
- •Has failed the first line chemotherapy (excluding adjuvant or neoadjuvant therapy) or targeted therapy for melanoma.
- •Has at least one measurable lesion as defined by RECIST 1.1 on imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]).
- •Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- •Has an anticipated life expectancy of at least 3 months.
- •Demonstrates adequate organ function.
- •Has provided tissue for anti-programmed cell death ligand-1 (PD-L1) expression evaluation from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
- •Has documented BRAF mutation status or is willing to provide a tumor tissue for BRAF genotyping.
- •Females may be enrolled in the study if they are:
- •Of non-childbearing potential which is defined as:
- •Is ≥45 years of age and has not had menses for greater than 2 years.
- •Is amenorrheic for <2 years without a hysterectomy and oophorectomy and has a follicle stimulating hormone (FSH) value in the postmenopausal range upon screening evaluation, and/or,
- •Is status post hysterectomy, oophorectomy or tubal ligation.
- •Female and male participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
排除标准
- •Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD-L1, anti-PD-L2 agents.
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug.
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or baseline) from AEs due to agents administered more than 4 weeks earlier.
- •Has had chemotherapy, targeted small molecule therapy, radiotherapy within 2 weeks prior to the first dose of study drug, or who has not recovered (i.e., ≤ Grade 1 or baseline) from AEs due to a previously administered agent.
- •Has a known history of another (including unknown primary) malignancy within 5 years prior to first dose of study drug. (Exceptions include adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, superficial bladder cancer, or cancer in situ which has undergone potentially curative therapy.)
- •Is expected to require any other form of systemic or localized antineoplastic therapy while in study.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- •Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study drug.
- •Has an active infection requiring intravenous systemic therapy.
- •Has received a live vaccine within 4 weeks prior to the first dose of study drug.
- •Has a known hypersensitivity to the components of the study drug or another mAb.
- •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- •Is known to be Human Immunodeficiency Virus (HIV) positive.
- •Has known active Hepatitis B or C.
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit (Visit 1) through 120 days after the last dose of study treatment.
结局指标
主要结局
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to approximately 17 months (through data cutoff date of 27-December-2017)
The number of all participants who discontinued study treatment due to an AE is presented.
Number of Participants Who Experienced At Least One Adverse Event (AE)
时间窗: Up to approximately 17 months (Through data cutoff date of 27-December-2017)
An AE was defined as any untoward medical occurrence in a participant administered a study treatment 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, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
时间窗: Up to approximately 17 months (through data cutoff date of 27-December-2017)
ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 assessed by blinded independent central review (BICR). The ORR per RECIST 1.1 for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants.
次要结局
- Overall Survival (OS)(Up to approximately 76 months)
- Duration of Response (DOR) by Immune-related Response Evaluation Criteria in Solid Tumors Version (irRECIST)(Up to approximately 76 months)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 2 (21-day Cycle)(Day 21: Prior to the Cycle 2 (21-day cycle) Dose)
- Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 1 (21-day Cycle)(Day 0: 30 minutes after the end of infusion during Cycle 1 (21-day cycle))
- Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 76 months)
- Objective Response Rate (ORR) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)(Up to approximately 76 months)
- Progression-free Survival (PFS) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)(Up to approximately 76 months)
- Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 76 months)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 6 (21-day Cycle)(Day 105: Prior to the Cycle 6 (21-day cycle) Dose)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 8 (21-day Cycle)(Day 147: Prior to the Cycle 8 (21-day cycle) Dose)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 16 (21-day Cycle)(Day 315: Prior to the Cycle 16 (21-day cycle) Dose)
- Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 8 (21-day Cycle)(Day 147: 30 minutes after the end of infusion during Cycle 8 (21-day cycle))
- Observed Serum Concentration of Pembrolizumab 14 Days After The End of Infusion During Cycle 1 (21-day Cycle)(Day 15: 14 days after the end of infusion during Cycle 1 (21-day cycle))
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 4 (21-day Cycle)(Day 63: Prior to the Cycle 4 (21-day cycle) Dose)
- Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 12 (21-day Cycle)(Day 231: Prior to the Cycle 12 (21-day cycle) Dose)
- Observed Serum Concentration of Pembrolizumab 1 Day After The End of Infusion During Cycle 1 (21-day Cycle)(Day 2: 1 day after the end of infusion during Cycle 1 (21-day cycle))
- Observed Serum Concentration of Pembrolizumab 5 Days After The End of Infusion During Cycle 1 (21-day Cycle)(Day 6: 5 days after the end of infusion during Cycle 1 (21-day cycle))