NCT04662710

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)

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)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 895 (actual)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess the efficacy and safety of lenvatinib (E7080/MK-7902) plus pembrolizumab (MK-3475) plus chemotherapy compared with chemotherapy alone in participants with advanced/metastatic gastroesophageal cancer. The primary study hypotheses are that lenvatinib plus pembrolizumab plus chemotherapy is superior to chemotherapy alone for both overall survival (OS) and 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 programmed cell death-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 and in all participants.

Detailed description

There will be 2 parts to the study: a Safety Run-in (Part 1) and the Main Study (Part 2). In Part 1 (Safety Run-in), approximately 12 participants will be treated with lenvatinib in combination with pembrolizumab and chemotherapy with either capecitabine and oxaliplatin (CAPOX), or 5-fluorouracil (5-FU), Leucovorin, and oxaliplatin (mFOLFOX6). Participants will be closely followed for dose-limiting toxicities for 21 days after the first dose of study intervention. In Part 2, up to 878 eligible participants (not including those participating in Part 1) will be randomly assigned in a 1:1 ratio to either lenvatinib plus pembrolizumab plus chemotherapy (CAPOX or mFOLFOX6) or Chemotherapy alone (CAPOX or mFOLFOX6). Participants can receive up to 18 infusions (up to 2 years) of pembrolizumab in the first course. Participants may be eligible to receive a second course of pembrolizumab (approximately 1 year) at the investigator's discretion. As of Amendment 8 (Effective 06/10/2025), Second Course will no longer be offered. Any participant currently receiving Second Course retreatment will be able to continue treatment as planned. Imaging will be performed per local standard of care.

Conditions

• Advanced/Metastatic Gastroesophageal Adenocarcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Pembrolizumab	400 mg Q6W by IV infusion
BIOLOGICAL	Lenvatinib	Administered PO QD, 8 mg induction/20 mg consolidation.
DRUG	Oxaliplatin	130 mg/m\^2 administered by IV infusion on Day 1 of Weeks 1 and 4 of each Q6W cycle as part of CAPOX chemotherapy, or 85 mg/m\^2 administered by IV infusion on Day 1 and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.
DRUG	Capecitabine	1000 mg/m\^2 administered PO twice daily (BID) on Days 1-14, 22-35 of each Q6W cycle as part of CAPOX chemotherapy.
DRUG	Leucovorin (or Levoleucovorin)	Administered by IV infusion at 400 mg/m\^2 (leucovorin) or 200 mg/m\^2 (levoleucovorin) on Day 1, and Week 1, 3 and 5 of each Q6W cycle as part of mFOLFOX6 chemotherapy.
DRUG	5-FU	400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous IV infusion administered on Day 1, and Week 1, 3, 5, of each Q2W cycle as part of mFOLFOX6 chemotherapy.

Timeline

• Start date: 2020-12-30
• Primary completion: 2024-10-29
• Completion: 2026-03-31
• First posted: 2020-12-10
• Last updated: 2025-11-28
• Results posted: 2025-11-28

Locations

177 sites across 24 countries: United States, Argentina, Australia, Belgium, Canada, Chile, China, Colombia, Costa Rica, France, Germany, Guatemala, Hong Kong, Ireland, Israel, Italy, Japan, Poland, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study