NCT04210115|Active Not RecruitingPhase 3DMCFDA Drug

Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975)

A Randomized, Double-blind, Placebo-controlled Phase 3 Trial of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Receiving Concurrent Definitive Chemoradiotherapy (KEYNOTE 975)

Merck Sharp & Dohme LLC ClinicalTrials.gov

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7 other identifiers

3475-975MK-3475-975KEYNOTE-975PHRR200210-0024902052612022-501531-162019-002006-51

Study Type

interventional

Target

703

Locations

27 countries

Sites

170

Timeline

RegisteredDec 2019

StartedFeb 2020

CompletionFeb 2027

Brief Summary

The purpose of this study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with dCRT + placebo with respect to Event-free Survival (EFS) and Overall Survival (OS) in:

participants whose tumors express Programmed Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10
participants whose tumors express PD-L1 CPS ≥1
all participants The primary study hypotheses are that dCRT+ pembrolizumab is better than dCRT + placebo with respect to:
EFS in participants whose tumors express PD-L1 CPS ≥10
EFS in participants whose tumors express PD-L1 CPS ≥1
EFS in all participants
OS in participants whose tumors express PD-L1 CPS ≥10
OS in participants whose tumors express PD-L1 CPS ≥1
OS in all participants

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

703

participants targeted

Target at P75+ for phase_3

Timeline

9mo left

Started Feb 2020

Longer than P75 for phase_3

Geographic Reach

27 countries

170 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.9 years study duration

Study Progress89%

Feb 2020Feb 2027

First Submitted

Initial submission to the registry

December 20, 2019

Completed

4 days until next milestone

First Posted

Study publicly available on registry

December 24, 2019

Completed

2 months until next milestone

Study Start

First participant enrolled

February 28, 2020

Completed

6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2027

Last Updated

November 15, 2024

Status Verified

November 1, 2024

Enrollment Period

6.9 years

First QC Date

December 20, 2019

Last Update Submit

November 13, 2024

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)Gastroesophageal Junction Carcinoma (GEJC)Esophageal Adenocarcinoma (EAC)

Keywords

Programmed Cell Death-1 (PD1, PD-1)Programmed Death-Ligand 1 (PDL1, PD-L1)Programmed Death-Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (2)

Event-free Survival (EFS)
EFS is defined as the time from randomization to an event defined as local, regional, or distant radiological recurrence as assessed by the investigator; clinical recurrence as assessed by the investigator with histopathologic confirmation (in the absence of radiological disease recurrence by investigator assessment); or death from any cause, whichever occurs first.
Up to ~60 months
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause.
Up to ~72 months

Secondary Outcomes (2)

Number of participants with an adverse event (AE)
Up to ~15 months
Number of participants discontinuing study treatment due to an adverse event (AE)
Up to ~12 months

Study Arms (2)

Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy

EXPERIMENTAL

Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)\] 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray \[Gy\] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year.

Biological: pembrolizumabDrug: cisplatinDrug: 5-FURadiation: radiotherapyDrug: leucovorinDrug: levoleucovorinDrug: oxaliplatin

Placebo+FP or FOLFOX Therapy+Radiotherapy

PLACEBO COMPARATOR

Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: * FP therapy: cisplatin 75 mg/m\^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m\^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m\^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR * FOLFOX therapy: oxaliplatin 85 mg/m\^2 AND either leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m\^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m\^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year.

Drug: placeboDrug: cisplatinDrug: 5-FURadiation: radiotherapyDrug: leucovorinDrug: levoleucovorinDrug: oxaliplatin

Interventions

pembrolizumabBIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy

placeboDRUG

IV infusion

Also known as: Normal saline solution

Placebo+FP or FOLFOX Therapy+Radiotherapy

cisplatinDRUG

IV infusion

Also known as: PLATINOL®