NCT03776136已完成2 期
A Multicenter, Open-label, Phase 2 Trial to Assess the Efficacy and Safety of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Melanoma Previously Exposed to an Anti-PD-1/L1 Agent (LEAP-004)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 23
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This study will evaluate the safety and efficacy of combination therapy of lenvatinib (E7080/MK-7902) and pembrolizumab following approximately 2 years of pembrolizumab therapy and approximately 2 years or more lenvatinib therapy in adult participants with unresectable or advanced melanoma who have been exposed to anti-programmed cell death ligand 1 (PD-1/L1) agents approved for unresectable or metastatic melanoma. No statistical hypothesis will be tested in this study.
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
- •Has histologically or cytologically confirmed melanoma
- •Has unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8 that is not amenable to local therapy
- •Has the presence of ≥1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 as confirmed by BICR.
- •Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies
- •Has submitted pre-trial imaging
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- •Has provided a baseline tumor biopsy
- •Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications from the Intervention
- •Male participants must agree to use approved contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period
- •Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study intervention
- •Has adequate organ function
排除标准
- •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 requires active treatment
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has ocular melanoma
- •Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- •Has an active infection requiring systemic therapy
- •Has known history of Human Immunodeficiency Virus (HIV) or HIV 1/2 antibodies
- •Has known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (HCV RNA qualitative] is detected)
- •Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
- •Has a history of active tuberculosis (Bacillus tuberculosis)
- •Has presence of a gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
- •Has had major surgery within 4 weeks prior to first dose of study interventions (adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility)
- •Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula
- •Has radiographic evidence of major blood vessel invasion/infiltration
- •Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
- •Has clinically significant cardiovascular disease within 12 months from first dose of study drug, 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 received prior radiotherapy within 2 weeks of Cycle 1 Day 1 with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks prior to Cycle 1 Day 1
- •Has received a live vaccine within 30 days before the first dose of study treatment
- •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 treatment
- •Has a history or has current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the 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 allogeneic tissue/solid organ transplant
- •Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
研究组 & 干预措施
lenvatinib plus pembrolizumab
Experimental
Participants receive lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.
干预措施: pembrolizumab (Biological)
lenvatinib plus pembrolizumab
Experimental
Participants receive lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.
干预措施: lenvatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to approximately 55 months
ORR was defined as the percentage of participants in the analysis population who have a confirmed Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: ≥30% decrease in the sum of target lesion diameters without progression in other lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR). Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ).
次要结局
- Progression-free Survival (PFS)(Up to approximately 55 months)
- Overall Survival (OS)(Up to approximately 55 months)
- Duration of Response (DOR)(Up to approximately 55 months)
- Area Under the Concentration Time Curve of Lenvatinib From Time 0 to Infinity (AUC 0-inf)(Cycle 1 Day 1: 0.5 to 4 hours and 6 to 10 hours postdose; Cycle 1 Day 15: Predose and 2 to 12 hours postdose; Cycle 2 Day 1: Predose, 0.5 to 4 hours, and 6 to 10 hours post-dose (each cycle =21 days))
- Number of Participants Who Experience At Least One Adverse Event (AE)(Up to approximately 55 months)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 48 months)
研究者
研究点 (23)
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