Clinical trial NCT04882241: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Gastroesophageal Junction Cancer
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-05-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
timeFrame: Up to approximately 42 months
measure: Pathological Complete Response (pathCR) Rate - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
timeFrame: Up to approximately 9 weeks following completion of neoadjuvant treatment (up to Study Week 18)
measure: Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
timeFrame: Up to approximately 42 months
measure: Number of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts
timeFrame: Up to approximately 42 months
measure: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts
timeFrame: Up to approximately 17 months
Secondary outcomes:
measure: Number of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
timeFrame: Up to approximately 42 months
measure: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
timeFrame: Up to approximately 23 months
measure: Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
timeFrame: Up to approximately 42 months
measure: Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
timeFrame: Up to approximately 42 months
measure: Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
timeFrame: Up to approximately 42 months
Other outcomes:
Locations:
city: Bengbu
country: China
facility: Afflilated Hospital of Bengbu Medical College-Surgical Oncology (Site 0638)
state: Anhui
city: Beijing
country: China
facility: Beijing Friendship Hospital ( Site 0637)
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital ( Site 0221)
state: Beijing
city: Fuzhou Fujian
country: China
facility: Fujian Medical University Union Hospital-1 Bingfanglou-Gastric Surgery Department (Site 0632)
state: Fujian
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital ( Site 0230)
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University (Site 0635)
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University ( Site 0224)
state: Guangdong
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University ( Site 0633)
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital (Site 0227)
state: Henan
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical College-Oncology ( Site 0645)
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University-Gastrointestinal Surgery ( Site 0234)
state: Jilin
city: Xi'an
country: China
facility: Tangdu Hospital of Fourth Military Medical University of Chinese People's Liberation Army ( Site 0647)
state: Shaanxi
city: Jinan
country: China
facility: Shandong Provincial Hospital-Gastrointestinal Surgery ( Site 0640)
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University ( Site 0636)
state: Shandong
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 0642)
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Cancer hospital
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital-Oncology (Site 0656)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 0231)
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital ( Site 0233)
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University (Site 0652)
state: Zhejiang
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: