2022-501342-29-00RecruitingPhase 3
A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared with Standard of Care as First-line Intervention in Participants with Metastatic Esophageal Carcinoma
Merck Sharp & Dohme LLC38 sites in 6 countries171 target enrollmentStarted: July 25, 2023Last updated:
Conditions
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 171
- Locations
- 38
- Primary Endpoint
- Part 1 (5-Fluorouracil [5-FU] plus cisplatin [FP] and paclitaxel plus cisplatin [TP] Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)
Study Overview
Brief Summary
- Part 1 (FP and TP Safety Run-in): To evaluate the safety and tolerability of treatment with lenvatinib + pembrolizumab in combination with FP or TP.
- Part 2 (Main Study): To compare OS between treatment arms.
Eligibility Criteria
- Ages
- 18 years to 65+ years (18-64 Years, 65+ Years)
- Accepts Healthy Volunteers
- Yes
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 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 or have had a history of radiation pneumonitis
- •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 locally advanced esophageal carcinoma
- •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
- •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
Outcomes
Primary Outcomes
Part 1 (5-Fluorouracil [5-FU] plus cisplatin [FP] and paclitaxel plus cisplatin [TP] Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)
Part 1 (5-Fluorouracil [5-FU] plus cisplatin [FP] and paclitaxel plus cisplatin [TP] Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)
Part 1 (FP and TP Safety Run-in): Number of Participants With Adverse Events (AEs)
Part 1 (FP and TP Safety Run-in): Number of Participants With Adverse Events (AEs)
Part 1 (FP and TP Safety Run-in): Number of Participants who Discontinued Study Treatment Due to an AE
Part 1 (FP and TP Safety Run-in): Number of Participants who Discontinued Study Treatment Due to an AE
Part 2 (Main Study): Overall Survival (OS) in all Participants
Part 2 (Main Study): Overall Survival (OS) in all Participants
Secondary Outcomes
- Part 2 (Main Study): 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 all Participants
- Part 2 (Main Study): Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR in all Participants
- Part 2 (Main Study): Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR in all Participants
- Part 2 (Main Study): OS in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10
- Part 2 (Main Study): PFS per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
- Part 2 (Main Study): ORR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
- Part 2 (Main Study): DOR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
- Part 2 (Main Study): Number of Participants With AEs
- Part 2 (Main Study): Number of Participants who Discontinued Study Treatment Due to an AE
- Part 2 (Main Study): Change From Baseline in Health-related Quality of life (HRQoL) Score Using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)
- Part 2 (Main Study): Change From Baseline in HRQoL Score Using EORTC Quality of Life Questionnaire-Oesophageal Module (QLQ-OES18)
- Part 2 (Main Study): Time to Deterioration (TTD) in HRQoL Score Using EORTC QLQ-C30
- Part 2 (Main Study): TTD in HRQoL Score Using EORTC QLQ-OES18
Investigators
Sucharita Bhaumik
Scientific
Merck Sharp & Dohme LLC
Study Sites (38)
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