2023-504834-23-00招募中4 期
A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Lenvatinib (E7080/MK-7902) plus Pembrolizumab (MK-3475) plus Chemotherapy Compared with Standard of Care Therapy as First-line Intervention in Participants with Advanced/Metastatic Gastroesophageal Adenocarcinoma (LEAP-015)
适应症
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 231
- 试验地点
- 37
- 主要终点
- Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
- Objective (Part 1): To evaluate the safety and tolerability of treatment with lenvatinib plus pembrolizumab plus chemotherapy.
- Objective (Part 2): To compare the overall survival between treatment groups.
- Objective (Part 2): To compare the PFS between treatment groups.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Has histologically and/or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma
- •Is not expected to require tumor resection during the treatment course
- •Has gastroesophageal adenocarcinoma that is not HER-2/neu positive
- •Has measurable disease as by RECIST 1.1 by scan with IV contrast as determined by the local site investigator
- •Male participants agree to refrain from donating sperm and agree to either remain abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for >7 days after last dose of lenvatinib or 90 days after last dose of chemotherapy-whichever comes last
- •Female participants not pregnant or breastfeeding are eligible to participate if not a women of childbearing potential (WOCBP), or if a WOCBP they either use a contraceptive method that is highly effective OR remain abstinent from heterosexual intercourse as their preferred and usual lifestyle, and do not donate eggs (ova,oocytes) to others or freeze/store for their own use, and abstain from breastfeeding during the intervention period through 120 days after last dose of pembrolizumab, 30 days after last dose of lenvatinib, or 180 days after last dose of chemotherapy-whichever occurs last
- •Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of study treatment
- •Has adequately controlled blood pressure with or without antihypertensive medications
- •Has adequate organ function
排除标准
- •Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ) esophageal adenocarcinoma
- •Has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- •Has received prior therapy with anti-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor or anti-VEGF mAb
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
- •Has radiographic evidence or encasement or invasion of a major blood vessel, or of intertumoral cavitation
- •Has inadequate cardiac function
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Has poorly controlled diarrhea
- •Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
- •Has peripheral neuropathy >Grade 2
- •Has had major surgery within 28 days prior to first dose of study interventions
- •Has a known history of human immunodeficiency virus (HIV) or HIV 1/2 antibodies
- •Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
- •Has weight loss of >20% within the last 3 months
- •Has had radiotherapy within 14 days of randomization
- •Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
- •Has known CNS metastases and/or carcinomatous meningitis
- •Has severe hypersensitivity (>Grade 3) to treatment with an monoclonal antibody (mAb) or known sensitivity or intolerance to any component of lenvatinib, pembrolizumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum containing products
- •Has had an allogeneic tissue/solid organ transplant
- •Has perforation risks or significant gastrointestinal (GI) bleeding
- •Has GI obstruction, poor oral intake (CAPOX participants), or difficulty in taking oral medication (CAPOX participants)
结局指标
主要结局
Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Part 1: Number of Participants with Adverse Events (AEs)
Part 1: Number of Participants with Adverse Events (AEs)
Part 1: Number of Participants who Discontinued Study Treatment Due to an AE
Part 1: Number of Participants who Discontinued Study Treatment Due to an AE
Part 2: Overall Survival (OS) in Participants with Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
Part 2: Overall Survival (OS) in Participants with Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
Part 2: OS in All Participants
Part 2: OS in All Participants
Part 2: 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) in Participants with PD-L1 CPS ≥1
Part 2: 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) in Participants with PD-L1 CPS ≥1
Part 2: PFS Per RECIST 1.1 as Assessed by BICR in All Participants
Part 2: PFS Per RECIST 1.1 as Assessed by BICR in All Participants
次要结局
- Part 2: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS ≥1
- Part 2: ORR Per RECIST 1.1 as Assessed by BICR in All Participants
- Part 2: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS ≥1
- Part 2: DOR Per RECIST 1.1 as Assessed by BICR in All Participants
- Part 2: Number of Participants with AEs
- Part 2: Number of Participants who Discontinued Study Treatment Due to an AE
研究者
Sonal Bordia
Scientific
Merck Sharp & Dohme LLC
研究点 (37)
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