NCT05064059已完成3 期
A Phase 3 Study of MK-4280A (Coformulated Favezelimab [MK-4280] Plus Pembrolizumab [MK-3475]) Versus Standard of Care in Previously Treated Metastatic PD-L1 Positive Colorectal Cancer (KEYFORM-007)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 441
- 试验地点
- 304
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of coformulated favezelimab/pembrolizumab (MK-4280A) in participants with metastatic colorectal cancer. The study will also compare MK-4280A with the standard of care treatment of regorafenib and TAS-102 (trifluridine and tipiracil).
The primary study hypothesis is that coformulated favezelimab/pembrolizumab (MK-4280A) is superior to standard of care with respect to overall survival.
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
盲法说明
None (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 confirmed colorectal adenocarcinoma that is metastatic and unresectable.
- •Has measurable disease per RECIST 1.1 as assessed by the local site investigator.
- •Has been previously treated for the disease and radiographically progressed on or after or could not tolerate standard treatment.
- •Submits an archival (≤ 5 years) or newly obtained tumor tissue sample or newly obtained tumor tissue sample that has not been previously irradiated.
- •Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1 within 10 days prior to first dose of study intervention.
- •Has a life expectancy of at least 3 months, based on the investigator assessment.
- •Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption.
- •Has adequate organ function.
排除标准
- •Has previously been found to have deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) tumor status.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease.
- •Has a history of acute or chronic pancreatitis.
- •Has neuromuscular disorders associated with an elevated creatine kinase (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
- •Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
- •Has urine protein greater than or equal to 1g/24h.
- •A woman of childbearing potential who has a positive urine/serum pregnancy test within 24/72 hours prior to the first dose of study intervention.
- •Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2), anti-lymphocyte activation gene 3 (LAG-3) antibody, with a tyrosine kinase inhibitor (TKI; eg, lenvatinib) other than rapidly accelerated fibrosarcoma (RAF) inhibitors (binimetinib is permitted if combined with a RAF inhibitor), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4, OX-40, cluster of differentiation [CD] 137).
- •Has previously received regorafenib or TAS-
- •Has received prior systemic anticancer therapy including investigational agents within 28 days before randomization.
- •Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •Has an active infection requiring systemic therapy (eg, tuberculosis, known viral or bacterial infections, etc.).
- •Has a known history of human immunodeficiency virus (HIV) infection.
- •Has known history of Hepatitis B or known active Hepatitis C virus infection.
- •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.
- •Has had an allogenic tissue/solid organ transplant.
研究组 & 干预措施
Favezelimab/Pembrolizumab
Experimental
Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) intravenously (IV) on Day 1, then every 3 weeks (Q3W), for up to 35 infusions.
干预措施: favezelimab/pembrolizumab (Biological)
Standard of Care (Regorafenib or TAS-102)
Active Comparator
At the Investigator's choice, participants will receive 160 mg regorafenib orally daily on Days 1-12 of each 28-day cycle or 35 mg/m^2 TAS-102 orally twice daily on Days 1-5 and Days 8-12 of each 28-day cycle.
干预措施: regorafenib (Drug)
Standard of Care (Regorafenib or TAS-102)
Active Comparator
At the Investigator's choice, participants will receive 160 mg regorafenib orally daily on Days 1-12 of each 28-day cycle or 35 mg/m^2 TAS-102 orally twice daily on Days 1-5 and Days 8-12 of each 28-day cycle.
干预措施: TAS-102 (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to approximately 33 months
OS was defined as the time from randomization to death due to any cause.
Overall Survival (OS)
时间窗: Up to approximately 33 months
OS was defined as the time from randomization to death due to any cause.
次要结局
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 28 months)
- Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 8 weeks)
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)(Up to approximately 21 months)
- Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 21 months)
- Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 21 months)
- Number of Participants Who Experienced at Least One Adverse Event (AE)(Up to approximately 31 months)
- Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score(Baseline and up to approximately 8 weeks)
- Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score(Baseline and up to approximately 8 weeks)
- Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score(Baseline and up to approximately 8 weeks)
- Time to Deterioration (TTD) in EORTC QLQ-C30 GHS (Item 29) and QoL (Item 30) Combined Score(Baseline and up to approximately 38 months)
- TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to approximately 38 months)
- TTD in in EORTC QLQ-C30 Appetite Loss (Item 13) Score(Baseline and up to approximately 38 months)
- TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score(Baseline and up to approximately 38 months)
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)(Up to approximately 21 months)
- Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 21 months)
- Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 21 months)
- Number of Participants Who Experienced at Least One Adverse Event (AE)(Up to approximately 31 months)
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 28 months)
- Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 8 weeks)
- Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score(Baseline and up to approximately 8 weeks)
- Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score(Baseline and up to approximately 8 weeks)
- Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score(Baseline and up to approximately 8 weeks)
- Time to Deterioration (TTD) in EORTC QLQ-C30 GHS (Item 29) and QoL (Item 30) Combined Score(Baseline and up to approximately 38 months)
- TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to approximately 38 months)
- TTD in in EORTC QLQ-C30 Appetite Loss (Item 13) Score(Baseline and up to approximately 38 months)
- TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score(Baseline and up to approximately 38 months)
研究者
研究点 (304)
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