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)

Official Title

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)

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 Tumours 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.

Trial Description

Primary Outcome:

• Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
• Part 1: Number of Participants with Adverse Events (AEs)
• 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: OS in All Participants
• Part 2: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumours 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

Secondary Outcome:

• 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: 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: Number of Participants with AEs
• Part 2: Number of Participants who Discontinued Study Treatment Due to an AE

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 778 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.

View this trial on ClinicalTrials.gov