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)-China Extension

Gastric Cancer Clinical Trial

Official 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04882241
• Other study ID #: 3475-585 China Extension
• Secondary ID: MK-3475-58517378
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 29, 2020
• Est. completion date: June 27, 2025

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated Chinese adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma. No formal hypothesis testing will be done.

Description:

The China extension study will include participants previously enrolled in China in the global study for MK-3475-585 (NCT03221426) plus those enrolled during the China extension enrollment period. A total of approximately 120 Chinese participants will be enrolled.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 115
• Est. completion date: June 27, 2025
• Est. primary completion date: February 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has previously untreated localized gastric or gastroesophageal junction (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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer
• Gastroesophageal Junction Cancer

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Placebo
IV infusion
• Cisplatin
IV infusion
• Capecitabine
Oral tablets
• 5-fluorouracil
IV infusion
• Docetaxel
IV infusion
• Oxaliplatin
IV infusion
• Leucovorin
IV infusion

Locations

Country	Name	City	State
China	Beijing Cancer Hospital ( Site 0221)	Beijing	Beijing
China	Beijing Friendship Hospital ( Site 0637)	Beijing	Beijing
China	Afflilated Hospital of Bengbu Medical College-Surgical Oncology (Site 0638)	Bengbu	Anhui
China	The First Hospital of Jilin University-Gastrointestinal Surgery ( Site 0234)	Changchun	Jilin
China	Sichuan Cancer hospital	Chengdu	Sichuan
China	Fujian Provincial Cancer Hospital ( Site 0230)	Fuzhou	Fujian
China	Fujian Medical University Union Hospital-1 Bingfanglou-Gastric Surgery Department (Site 0632)	Fuzhou Fujian	Fujian
China	The First Affiliated Hospital of Guangzhou Medical University ( Site 0224)	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University (Site 0635)	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital ( Site 0233)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 0231)	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital-Oncology (Site 0656)	Hangzhou	Zhejiang
China	Shandong Provincial Hospital-Gastrointestinal Surgery ( Site 0640)	Jinan	Shandong
China	The Affiliated Hospital of Qingdao University ( Site 0636)	Qingdao	Shandong
China	Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 0642)	Shanghai	Shanghai
China	Fourth Hospital of Hebei Medical University ( Site 0633)	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Wenzhou Medical University (Site 0652)	Wenzhou	Zhejiang
China	Tangdu Hospital of Fourth Military Medical University of Chinese People's Liberation Army ( Site 0647)	Xi'an	Shaanxi
China	The Affiliated Hospital of Xuzhou Medical College-Oncology ( Site 0645)	Xuzhou	Jiangsu
China	Henan Cancer Hospital (Site 0227)	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms	EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.	Up to approximately 63 months
Primary	Pathological Complete Response (pathCR) Rate - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms	PathCR rate is defined as the percentage of participants having a pathCR. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes.	Up to approximately 15 weeks
Primary	Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms	OS is defined as the time from randomization to death due to any cause.	Up to approximately 63 months
Primary	Percentage of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience at least one AE will be presented.	Up to approximately 20 months
Primary	Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 17 months
Secondary	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	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience at least one AE will be presented.	Up to approximately 20 months
Secondary	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	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 17 months
Secondary	Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms	DFS is defined as the time from post-surgery baseline scan until the first occurrence of local/distant recurrence or death from any cause and is based on RECIST 1.1 as assessed by the investigator.	Up to approximately 63 months
Secondary	Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms and Pembrolizumab+FLOT and Placebo+FLOT Cohorts	OS is defined as the time from randomization to death due to any cause.	Up to approximately 63 months
Secondary	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	EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by CT scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.	Up to approximately 63 months

External Links

•   Merck Clinical Trials Information