Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-7902-015/E7080-G000-321/LEAP-015) (LEAP-015)
- Conditions
- Advanced/Metastatic Gastroesophageal Adenocarcinoma
- Registration Number
- 2023-504834-23-00
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
1. Objective (Part 1): To evaluate the safety and tolerability of treatment with lenvatinib plus pembrolizumab plus chemotherapy.
2. Objective (Part 2): To compare the overall survival between treatment groups.
3. Objective (Part 2): To compare the PFS between treatment groups.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Not specified
- Target Recruitment
- 231
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
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)
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method Part 2: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS ≥1 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: 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: 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: DOR Per RECIST 1.1 as Assessed by BICR in All Participants
Part 2: Number of Participants with AEs Part 2: Number of Participants with AEs
Part 2: Number of Participants who Discontinued Study Treatment Due to an AE Part 2: Number of Participants who Discontinued Study Treatment Due to an AE
Trial Locations
- Locations (37)
UZ Leuven
🇧🇪Leuven, Belgium
CHU UCL Namur
🇧🇪Yvoir, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Algemeen Ziekenhuis Delta
🇧🇪Roeselare, Belgium
St James's Hospital
🇮🇪Dublin 8, Ireland
Beaumont Hospital
🇮🇪Dublin 9, Ireland
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
🇮🇹Meldola, Italy
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
🇮🇹Naples, Italy
Fondazione IRCCS Istituto Nazionale Dei Tumori
🇮🇹Milan, Italy
Azienda Unita' Locale Socio Sanitaria N. 8 Berica
🇮🇹Vicenza, Italy
Scroll for more (27 remaining)UZ Leuven🇧🇪Leuven, BelgiumJeroen DekervelSite contact+3216344225jeroen.dekervel@uzleuven.be