Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma (MK-7902-014/E7080-G000-320/LEAP-014)

Ведущий спонсор: Merck Sharp & Dohme Corp.

Коллаборационист: Eisai Inc.

The purpose of this study is to assess the efficacy and safety of pembrolizumab plus lenvatinib plus chemotherapy compared with pembrolizumab plus chemotherapy as first-line intervention in participants with metastatic esophageal carcinoma The primary hypotheses are that pembrolizumab plus lenvatinib plus chemotherapy is superior to pembrolizumab plus chemotherapy with respect to overall survival (OS) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

There will be 2 parts to the study: the cisplatin and 5-fluorouracil (5-FU) (FP) Safety Run-in (Part 1) and the Main Study (Part 2). In Part 1 (FP Safety Run-in), participants will be treated with pembrolizumab plus lenvatinib plus FP. Dose-limiting toxicities, safety, and tolerability will be assessed. In Part 2 (Main Study), participants (not including those participating in Part 1) will be treated with pembrolizumab plus lenvatinib plus chemotherapy or pembrolizumab plus chemotherapy. Efficacy, safety, and tolerability will be assessed.

• Metastatic Esophageal Squamous Cell Carcinoma

Тип вмешательства: Drug

Название вмешательства: Pembrolizumab

Описание: 400 mg once every 6-week-cycle, via IV infusion.

Тип вмешательства: Drug

Название вмешательства: Lenvatinib

Описание: 8 mg QD (induction) or 20 mg QD (consolidation) via oral capsule.

Этикетка Arm Group: Pembrolizumab + Lenvatinib + Chemotherapy

Тип вмешательства: Drug

Название вмешательства: Cisplatin

Описание: 80 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy.

Другое имя: PLATINOL®

Тип вмешательства: Drug

Название вмешательства: 5-FU

Описание: 4000 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy or 400 mg/m^2 Q2W via bolus IV infusion followed by 2400 mg/m^2 Q2W via continuous IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.

Другое имя: ADRUCIL®

Тип вмешательства: Drug

Название вмешательства: Oxaliplatin

Описание: 85 mg/m^2 Q2W via IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.

Другое имя: ELOXATIN®

Тип вмешательства: Drug

Название вмешательства: Leucovorin

Описание: 400 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.

Тип вмешательства: Drug

Название вмешательства: Levoleucovorin

Описание: 200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.

Критерии:

Inclusion Criteria: - Has a histologically or cytologically confirmed diagnosis of metastatic squamous cell carcinoma of the esophagus - Male participants are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or 90 days after the last dose of chemotherapy, whichever comes last; 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only and is greater than 90 days post chemotherapy, no male contraception is needed - Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 120 days after the last dose of pembrolizumab, 30 days after the last dose of lenvatinib, or 180 days after the last dose of chemotherapy, whichever occurs last, and agrees not to donate eggs during this period - Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP≤150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week prior to randomization - Has adequate organ function Exclusion Criteria: - Has had previous therapy for locally advanced unresectable or metastatic esophageal cancer - Has locally advanced esophageal carcinoma - Has metastatic adenocarcinoma of the esophagus - Has direct invasion into adjacent organs such as the aorta or trachea - Has radiographic evidence of encasement of a major blood vessel, or of intratumoral cavitation - Has perforation risks or significant gastrointestinal (GI) bleeding - Has had clinically significant hemoptysis within 3 weeks prior to the first dose of study drug or tumor bleeding within 2 weeks prior to the first dose of study intervention - Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention - Has GI obstruction, poor oral intake, difficulty in taking oral medication, or existing esophageal stent - Has had major surgery, open biopsy, or significant traumatic injury within 3 weeks prior to first dose of study interventions - Has received prior radiotherapy within 2 weeks of start of study intervention - Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed - Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention, or has a history of organ transplant, including allogeneic stem cell transplant - Has a known additional malignancy that is progressing or has required active treatment within the past 3 years - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Has an active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed - Has a history of non-infectious pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease - Has poorly controlled diarrhea - Has clinically significant cardiovascular disease within 12 months from first dose of study intervention - Has peripheral neuropathy ≥Grade 2 - Has a known history of human immunodeficiency virus (HIV) infection - Has a known history of Hepatitis B or know active Hepatitis C virus infection - Has a weight loss of >20% within the last 3 months

Пол:

All

Минимальный возраст:

18 Years

Максимальный возраст:

N/A

Здоровые волонтеры:

No

Фамилия: Toll Free Number

Телефон: 1-888-577-8839

Chile

China

Costa Rica

Denmark

France

Guatemala

Italy

Japan

Korea, Republic of

Russian Federation

Spain

Taiwan

Turkey

Ukraine

United States

2022-01-01

Тип: Sponsor

• programmed cell death 1 (PD-1, PD1)
• programmed cell death ligand 1 (PD-L1, PDL1)

• Carcinoma
• Esophageal Squamous Cell Carcinoma
• Esophageal Neoplasms

Метка: Pembrolizumab + Lenvatinib + Chemotherapy

Тип: Experimental

Описание: Participants will receive pembrolizumab intravenously (IV) plus lenvatinib orally in combination with FP in Part 1, or in combination with investigator's choice of chemotherapy with FP IV or oxaliplatin, 5-FU and leucovorin (mFOLFOX6) IV in Part 2. Induction will consist of pembrolizumab 400 mg once every 6-week-cycle (Q6W) for up to 2 cycles (up to ~12 weeks) plus lenvatinib 8 mg once daily (QD) for up to ~12 weeks plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2 once every 3 weeks [Q3W] for up to 4 administrations [up to ~12 weeks]) or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for up to 6 administrations [up to ~12 weeks]). This is followed by consolidation with pembrolizumab 400 mg Q6W for up to 16 cycles (each cycle = 6 weeks; total pembrolizumab treatment duration is ~2 years) plus lenvatinib 20 mg QD until progressive disease or discontinuation.

Метка: Pembrolizumab + Chemotherapy

Тип: Active Comparator

Описание: Participants will receive pembrolizumab 400 mg IV Q6W for up to 18 cycles (each cycle = 6 weeks; total pembrolizumab treatment duration is ~2 years) in combination with investigator's choice of chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 12 administrations [up to ~24 weeks, based on local guidance]), during Part 2.

Распределение: Randomized

Модель вмешательства: Parallel Assignment

Первичное назначение: Treatment

Маскировка: None (Open Label)