Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)

• Register: ClinicalTrials.gov
• Last refreshed on: 18 March 2024
• Main ID: NCT03221426
• Date of registration: 17/07/2017
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme LLC
• Public title: Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)
• Scientific title: A Phase III, Randomized, Double-Blind, Clinical Trial of Pembrolizumab (MK-3475) Plus Chemotherapy (XP or FP) Versus Placebo Plus Chemotherapy (XP or FP) as Neoadjuvant/Adjuvant Treatment for Subjects With Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma (KEYNOTE-585)
• Date of first enrolment: October 9, 2017
• Target sample size: 1007
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03221426
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Estonia, France, Germany, Guatemala, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, New Zealand, Philippines, Poland, Russian Federation, Singapore, Spain, Taiwan, Ukraine, United Kingdom, United States

Contacts

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

Key inclusion & exclusion criteria

Inclusion Criteria:

- Has previously untreated localized gastric or GEJ adenocarcinoma as defined by T3 or
greater primary lesion or the presence of any positive nodes - N+ (clinical nodes)
without evidence of metastatic disease.

- Plans to proceed to surgery following pre-operative chemotherapy based on standard
staging studies per local practice.

- Is willing to provide tissue from a tumor lesion at baseline and at time of surgery.

- Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1
within 3 days prior to the first dose of study treatment.

- Has adequate organ function.

- Male participants of childbearing potential must agree to use an adequate method of
contraception for the course of the study through 180 days after the last dose of
chemotherapy.

- Female participants of childbearing potential must be willing to use an adequate
method of contraception for the course of the study through 180 days after the last
dose of chemotherapy or through 120 days after the last dose of pembrolizumab,
whichever is greater.

- Has life expectancy of greater than 6 months.

Exclusion Criteria:

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.

- Has an active infection requiring systemic therapy.

- Is currently participating in or has participated in a trial of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study treatment.

- Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1),
anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic
T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily
member 4 [OX-40], necrosis factor receptor superfamily member 9 [CD137]) or has
previously participated in a Merck pembrolizumab (MK-3475) clinical trial.

- Has received prior systemic anti-cancer therapy including investigational agents for
the current malignancy.

- 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 14 days prior the first dose of study treatment.

- Has a known additional malignancy that is progressing or has required active treatment
within the past 5 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ that have undergone
potentially curative therapy are not excluded.

- Has a known severe hypersensitivity (= Grade 3) to pembrolizumab, its active substance
and/or any of its excipients, or to any of the study chemotherapy agents and/or to any
of their excipients.

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

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has a known history of Hepatitis B or known active Hepatitis C virus infection.

- Has a known history of active tuberculosis (TB).

- Female participants who are pregnant or breastfeeding or expecting to conceive
children within the projected duration of the study, starting with the screening visit
through180 days after the last dose of chemotherapy or through 120 days after the last
dose of pembrolizumab, whichever is greater.

- Male participants who are expecting to father children within the projected duration
of the study, starting with the screening visit through 180 days after the last dose
of chemotherapy.

- Has had an allogenic tissue/solid organ transplant.

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



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

Health Condition(s) or Problem(s) studied

Gastric Cancer

Gastroesophageal Junction Cancer

Intervention(s)

Drug: Oxaliplatin

Drug: Capecitabine

Drug: Cisplatin

Drug: Docetaxel

Biological: Pembrolizumab

Drug: 5-fluorouracil

Drug: Placebo

Drug: Leucovorin

Primary Outcome(s)

Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms [Time Frame: Up to approximately 2 years]

Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms [Time Frame: Up to approximately 2 years]

Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts [Time Frame: Up to approximately 2 years]

Pathological Complete Response (pathCR) Rate - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms [Time Frame: Up to approximately 15 weeks]

Percentage of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts [Time Frame: Up to approximately 27 months]

Secondary Outcome(s)

Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms [Time Frame: Up to approximately 2 years]

Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms and Pembrolizumab+FLOT and Placebo+FLOT Cohorts [Time Frame: Up to approximately 2 years]

Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms Separately and in Combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts [Time Frame: Up to approximately 2 years]

Percentage of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms Separately and in Combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts [Time Frame: Up to approximately 27 months]

Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms and Pembrolizumab+FLOT and Placebo+FLOT Cohorts [Time Frame: Up to approximately 2 years]

Secondary ID(s)

MK-3475-585

3475-585

PHRR200226-002534

KEYNOTE-585

173786

2016-004408-76

Source(s) of Monetary Support

Please refer to primary and secondary sponsors