A Phase Ib Clinical Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With Cisplatin and Pemetrexed in Treatment-naive Participants With Advanced Malignant Pleural Mesothelioma (KEYNOTE-A17).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 4
- 主要终点
- Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 1, Per Common Terminology Criteria for Adverse Events (AEs), Version 5.0 (CTCAE)
研究概览
简要总结
This is a multicenter, open-label, non-randomized, study of pembrolizumab in combination with cisplatin and pemetrexed in treatment of naïve participants with a histologically confirmed diagnosis of advanced/unresectable malignant pleural mesothelioma (MPM) in Japanese participants. This study will evaluate the safety, tolerability, and preliminary efficacy of pembrolizumab in combination with cisplatin and pemetrexed. The primary objective is to evaluate the safety and tolerability of treatment with pembrolizumab in combination with cisplatin and pemetrexed.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has histologically confirmed diagnosis of advanced/unresectable malignant pleural mesothelioma (MPM)
- •Have at least one measurable disease, which is systemic therapy naïve, radiologically assessed by the local site investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) using imaging scanned within 28 days prior to the first dose in this study
- •Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- •Has a life expectancy of at least 3 months
- •Demonstrate adequate organ function
- •Male participants are eligible to participate if they agree to remain abstinent or agree to use contraception unless confirmed to be azoospermic
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, using contraceptives or is not a woman of child bearing potential (WOCBP)
排除标准
- •A WOCBP who has a positive pregnancy test within 72 hours prior to treatment allocation
- •Has received prior therapy with an anti-programmed cell-death 1 (anti PD-1), anti programmed cell-death ligand 1 (anti-PD-L1), or anti programmed cell-death ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- •Has previously received systemic anti-cancer therapy (including investigational agents) for MPM
- •Participants who received (neo) adjuvant previously may be eligible, only if the last dose of chemotherapy was completed at least 6 months before registration. Such participants must have recovered from all adverse events (AEs) due to previous (neo) adjuvant therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible
- •Received radiation therapy to the lung that is > 30 gray (Gy) within 6 months of the first dose of trial treatment
- •Completed palliative radiotherapy within 7 days of the first dose of trial treatment
- •Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
- •Had a major surgery within 3 months prior to the first administration in this study
- •Has received a live vaccine within 30 days prior to the first dose of study drug
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
- •Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has had a severe hypersensitivity reaction (≥Grade 3) to treatment a monoclonal antibody/components of the study intervention
- •Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Is being treated for pericardial effusion, or has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible
- •Has an active infection requiring systemic therapy
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
研究组 & 干预措施
Pembrolizumab + Cisplatin + Pemetrexed
Pembrolizumab 200 mg IV every 3 weeks (Q3W) in combination with Cisplatin 75 mg/m^2 IV, and Pemetrexed 500 mg/m^2 IV for 4-6 cycles followed by monotherapy of Pembrolizumab up to 35 cycles from the first dose of the study in treatment phase (approximately 2 years).
干预措施: Cisplatin (Drug)
Pembrolizumab + Cisplatin + Pemetrexed
Pembrolizumab 200 mg IV every 3 weeks (Q3W) in combination with Cisplatin 75 mg/m^2 IV, and Pemetrexed 500 mg/m^2 IV for 4-6 cycles followed by monotherapy of Pembrolizumab up to 35 cycles from the first dose of the study in treatment phase (approximately 2 years).
干预措施: Pembrolizumab (Drug)
Pembrolizumab + Cisplatin + Pemetrexed
Pembrolizumab 200 mg IV every 3 weeks (Q3W) in combination with Cisplatin 75 mg/m^2 IV, and Pemetrexed 500 mg/m^2 IV for 4-6 cycles followed by monotherapy of Pembrolizumab up to 35 cycles from the first dose of the study in treatment phase (approximately 2 years).
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 1, Per Common Terminology Criteria for Adverse Events (AEs), Version 5.0 (CTCAE)
时间窗: Up to 3 weeks (through Cycle 1 [21 days])
DLTs were assessed during Cycle 1 (21 days) and defined as any of the following, if considered by investigator to be related to any of the study interventions: Grade 4 hematologic toxicities, except neutropenia and febrile neutropenia; Grade 4 neutropenia lasting \>7 days despite appropriate supportive treatment; Grade 4 febrile neutropenia only if the event considered as clinically significant by investigator and sponsor; any Grade 4 non-hematologic toxicity (except laboratory test abnormal including transient electrolyte abnormalities); any Grade 3 non-hematologic toxicity lasting \>72 hours despite appropriate supportive treatment (not laboratory); and any Grade 4 laboratory test value abnormality; any Grade 3 laboratory test value abnormality lasting \>7 days; delay in start of second course of more than 2 weeks (more than 35 days after the first dose) due to toxicity related to study procedures; any Grade 5 toxicity.
Number of Participants With One or More Adverse Events (AEs)
时间窗: Up to approximately 34 months
An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE.
Number of Participants Discontinuing Study Treatment Due to an AE
时间窗: Up to approximately 2 years
An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE.
次要结局
- Objective Response Rate (ORR)(Up to approximately 31 months)
- Disease Control Rate (DCR)(Up to approximately 31 months)
- Duration of Response (DOR)(Up to approximately 31 months)