First-line Esophageal Carcinoma Study With Chemo vs. Chemo Plus Pembrolizumab (MK-3475-590/KEYNOTE-590)

• Register: ClinicalTrials.gov
• Last refreshed on: 7 August 2023
• Main ID: NCT03189719
• Date of registration: 14/06/2017
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme LLC
• Public title: First-line Esophageal Carcinoma Study With Chemo vs. Chemo Plus Pembrolizumab (MK-3475-590/KEYNOTE-590)
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial of Pembrolizumab (MK-3475) in Combination With Cisplatin and 5-Fluorouracil Versus Placebo in Combination With Cisplatin and 5-Fluorouracil as First-Line Treatment in Subjects With Advanced/Metastatic Esophageal Carcinoma (KEYNOTE-590)
• Date of first enrolment: July 25, 2017
• Target sample size: 749
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03189719
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Denmark, France, Germany, Guatemala, Hong Kong, Japan, Korea, Republic of, Malaysia, Peru, Romania, Russian Federation, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme LLC

Key inclusion & exclusion criteria

Inclusion Criteria:

- Has histologically- or cytologically-confirmed diagnosis of locally advanced
unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus
or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction
(EGJ)

- Has measurable disease per RECIST 1.1 as determined by the local site
investigator/radiology assessment

- Eastern Cooperative Group (ECOG) performance status of 0 to 1

- Can provide either a newly obtained or archival tissue sample for PD-L1 by
immunohistochemistry analysis

- Female participants of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to randomization and be willing to use an
adequate method of contraception (e.g. abstinence, intrauterine device, diaphragm with
spermicide, etc.) for the course of the study through 120 days after the last dose of
study treatment and up to 180 days after last dose of cisplatin

- Male participants of childbearing potential must agree to use an adequate method of
contraception (e.g. abstinence, vasectomy, male condom, etc.) starting with the first
dose of study treatment through 120 days after the last dose of study treatment and up
to 180 days after last dose of cisplatin, and refrain from donating sperm during this
period

- Has adequate organ function

Exclusion Criteria:

- Has locally advanced esophageal carcinoma that is resectable or potentially curable
with radiation therapy (as determined by local investigator)

- Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cell
cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the
EGJ

- Has had major surgery, open biopsy, or significant traumatic injury within 28 days
prior to randomization, or anticipation of the need for major surgery during the
course of study treatment

- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with
curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, in situ cervical cancer, in situ breast cancer that has undergone potentially
curative therapy, and in situ or intramucosal pharyngeal cancer

- Has known active central nervous system metastases and/or carcinomatous meningitis.

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study treatment, or
has a history of organ transplant, including allogeneic stem cell transplant

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis, or has an active infection requiring systemic therapy

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study medication and up to 180 days after last dose of
cisplatin

- Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1),
anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory
T-cell receptor or has previously participated in a pembrolizumab (MK-3475) clinical
trial

- Has severe hypersensitivity (= Grade 3) to any study treatment (pembrolizumab,
cisplatin, or 5-FU) and/or any of its excipients

- Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis) or human
immunodeficiency virus (HIV) infection

- Has known history of or is positive for hepatitis B or hepatitis C

- Has received a live vaccine within 30 days prior to the first dose of study treatment

- Has had radiotherapy within 14 days of randomization. Participants who received
radiotherapy >14 days prior to randomization must have completely recovered from any
radiotherapy-related AEs/toxicities



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Esophageal Neoplasms

Intervention(s)

Drug: 5-FU

Drug: Placebo

Drug: Cisplatin

Biological: Pembrolizumab

Primary Outcome(s)

PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed By Investigator in Participants With ESCC [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

OS in All Participants [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

OS in Participants With ESCC [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

PFS Per RECIST 1.1 As Assessed By Investigator in All Participants [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

Overall Survival (OS) in Participants With Esophageal Squamous Cell Carcinoma (ESCC) Whose Tumors Are Programmed Cell Death-Ligand 1 (PD-L1) Biomarker-Positive (Combined Positive Score [CPS] =10) [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

Secondary Outcome(s)

Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Baseline, Week 18]

Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Baseline, Week 18]

ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC [Time Frame: Baseline, Week 18]

Change From Baseline To Week 18 in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Combined Score in All Participants [Time Frame: Baseline, Week 18]

Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

DOR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC [Time Frame: Baseline, Week 18]

Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Baseline, Week 18]

Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants [Time Frame: Baseline, Week 18]

Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10) [Time Frame: Baseline, Week 18]

DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC [Time Frame: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)]

Number of Participants With an Adverse Event (AE) [Time Frame: Up to approximately 28 months]

Number of Participants Discontinuing Study Treatment Due to an AE [Time Frame: Up to approximately 27 months]

Secondary ID(s)

MK-3475-590

3475-590

KEYNOTE-590

173739

2017-000958-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 06/07/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03189719