KEYMAKER-U01 Substudy 3: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents in Combination With Pembrolizumab in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) Previously Treated With Anti-PD-(L)1 Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 78
- 主要终点
- Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with boserolimab (MK-5890), MK-4830, MK-0482 in participants with advanced squamous or non-squamous NSCLC that have been previously treated with anti-PD-L1 therapy.
This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).
详细描述
The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798
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
- •Has a histologically- or cytologically-confirmed diagnosis of Stage IV squamous or non-squamous NSCLC.
- •Has non-squamous NSCLC and is not eligible for an approved targeted therapy.
- •Is able to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation
- •Have progressed on treatment with an anti-PD-(L)1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies
- •Have progressive disease (PD) during/after platinum doublet chemotherapy
- •Is able to complete all screening procedures within the 35-day screening window
- •Male participants must agree to use contraception and refrain from donating sperm during the treatment period and for at least 120 days after the last dose of study treatment
- •Female participants must not be pregnant or breastfeeding, and at least one of the following conditions apply:
- •Not a woman of childbearing potential (WOCBP) OR
- •A WOCBP who agrees to use contraception during the treatment period and for at least 120 days after the last dose of study treatment
- •Has adequate organ function within 10 days of initiation of study treatment
排除标准
- •Has a diagnosis of small cell lung cancer
- •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 before the first dose of study treatment
- •Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years
- •Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
- •Has an active infection requiring systemic therapy
- •Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment, or New York Heart Association Class III or IV congestive heart failure
- •Has a known history of Human Immunodeficiency Virus (HIV) infection
- •Has a known history of Hepatitis B or known active Hepatitis C virus infection
- •Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
- •Has had major surgery <3 weeks before the first dose of study treatment
- •Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment
- •Has received a live vaccine within 30 days before the first dose of study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed
- •Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
- •Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose of study treatment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks before the first dose of study treatment (including participants who had previous immunomodulatory therapy with residual irAEs)
- •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 treatment
- •Has participated in Substudies 1 or 2
- •Has had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
- •Is pregnant or 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 had an allogenic tissue/solid organ transplant
研究组 & 干预措施
Boserolimab + Pembrolizumab
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
干预措施: Pembrolizumab (Biological)
Boserolimab + Pembrolizumab
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
干预措施: Boserolimab (Biological)
Boserolimab + Pembrolizumab
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
干预措施: diphenhydramine (Drug)
Boserolimab + Pembrolizumab
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
干预措施: acetaminophen (Drug)
Pembrolizumab + MK-4830
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-4830 IV for a maximum of 35 cycles (approximately 2 years).
干预措施: MK-4830 (Biological)
Pembrolizumab + MK-4830
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-4830 IV for a maximum of 35 cycles (approximately 2 years).
干预措施: Pembrolizumab (Biological)
Pembrolizumab + MK-0482
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-0482 IV for a maximum of 35 cycles (approximately 2 years).
干预措施: MK-0482 (Biological)
Pembrolizumab + Boserolimab
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
干预措施: diphenhydramine (Drug)
Pembrolizumab + Boserolimab
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
干预措施: Boserolimab (Biological)
Pembrolizumab + Boserolimab
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
干预措施: acetaminophen (Drug)
Pembrolizumab + MK-0482
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-0482 IV for a maximum of 35 cycles (approximately 2 years).
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Boserolimab
On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
时间窗: Up to approximately 24 months
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.
次要结局
- Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 24 months)
- Number of Participants Who Experience One or More Adverse Events (AEs)(Up to approximately 27 months)
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)(Up to approximately 24 months)