Clinical trial NCT04859582: Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)-China Extension
Official title: A Phase 3, Randomized, Double-blind Clinical Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-line Treatment in Participants With HER2 Negative, Previously Untreated, Unresectable or Metastatic Gastric Orgastroesophageal Junction Adenocarcinoma (KEYNOTE-859)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Stomach Neoplasms
Keywords: programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
programmed cell death ligand 2 (PD-L2, PDL2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-04-26
Enrollment: 0
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 combination with chemotherapy (Cisplatin combined with 5-Fluorouracil \[FP regimen\] or oxaliplatin combined with capecitabine \[CAPOX regimen\]) versus placebo in combination with chemotherapy (FP or CAPOX regimens) in the treatment of human epidermal growth factor receptor 2 (HER2) negative advanced gastric or GEJ adenocarcinoma in adult Chinese participants.

The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS).

Detailed description: The China extension study will include participants previously enrolled in China in the global study for MK-3475-859 (NCT03675737) plus those enrolled during the China extension enrollment period. A total of approximately 231 Chinese participants will be enrolled.

Eligibility criteria: Inclusion Criteria

* Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with known programmed cell death ligand 1 (PD-L1) expression status
* Has human epidermal growth factor receptor 2 (HER2) negative cancer
* Male participants must agree to use contraception during the intervention period and for at least 95 days after the last dose of chemotherapy, refrain from donating sperm and be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or must agree to use contraception per study protocol unless confirmed to be azoospermic during this period
* Female participants who are not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) OR is a WOCBP who agrees to use contraception or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for at least 180 days after the last dose of chemotherapy or for at least 120 days after the last dose of pembrolizumab, whichever is last, and agrees not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period
* Has measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator assessment
* Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
* Has provided tumor tissue sample deemed adequate for PD-L1 biomarker analysis
* Has provided tumor tissue sample for microsatellite instability (MSI) biomarker analysis
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the start of study intervention
* Has adequate organ function as demonstrated by laboratory testing within 10 days prior to the start of study treatment

Exclusion Criteria

* Has squamous cell or undifferentiated gastric cancer
* Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, anticipation of the need for major surgery during the course of study intervention, or has not recovered adequately from the toxicity and/or complications from previous surgery
* Has preexisting peripheral neuropathy \>Grade 1
* Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation
* Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant and/or adjuvant therapy as long as it was completed ≥6 months prior to randomization
* Has received prior therapy with an anti-PD-1, anti-PD-L1 or anti- PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX- 40, CD137)
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization or has not recovered from all AEs due to any previous therapies to ≤Grade 1 or baseline
* Has received prior radiotherapy within 2 weeks prior to study start or has not recovered from all previous radiation-related toxicities, required corticosteroids, and have not had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to noncentral nervous system (CNS) disease
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
* Has a known additional malignancy that is progressing or has required active treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
* Has known active CNS metastases and/or carcinomatous meningitis
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as Hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] detected qualitatively) infection
* Has a known history of active tuberculosis
* Has hypokalemia (serum potassium less than the lower limit of normal)
* Has hypomagnesemia (serum magnesium less than the lower limit of normal)
* Has hypocalcemia (serum calcium less than the lower limit of normal)
* Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is last
* Has had an allogenic tissue/solid organ transplant
* Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents (including, but not limited to, infusional 5-fluorouracil or oral capecitabine) and/or to any of their excipients
* For participants taking cisplatin: has Grade ≥2 audiometric hearing loss

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 65 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 65 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 65 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 65 months
measure: Percentage of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to approximately 65 months
measure: Percentage of Participants Discontinuing Study Drug Due to AEs
timeFrame: Up to approximately 36 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences ( Site 2421)
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital ( Site 2425)
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital ( Site 2410)
state: Fujian
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital ( Site 2414)
state: Fujian
city: Fuzhou
country: China
facility: 900 Hospital of the Joint ( Site 2418)
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University ( Site 2430)
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital Xiamen University ( Site 2447)
state: Fujian
city: Guangzhou
country: China
facility: Guangdong General Hospital ( Site 2431)
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital ( Site 2442)
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital ( Site 2401)
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital ( Site 2415)
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital ( Site 2434)
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central-South University ( Site 2419)
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 2439)
state: Hunan
city: Changzhou
country: China
facility: Changzhou Cancer Hospital-Changzhou Fourth Peoples Hospital ( Site 2441)
state: Jiangsu
city: Nanjing
country: China
facility: The 81st Hospital of PLA ( Site 2413)
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital ( Site 2432)
state: Jiangsu
city: Yancheng
country: China
facility: Yancheng First People s Hospital ( Site 2426)
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University ( Site 2440)
state: Jiangxi
city: Chang chun
country: China
facility: The First Hospital of Jilin University ( Site 2416)
state: Jilin
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University ( Site 2405)
state: Shandong
city: Shanghai
country: China
facility: Shanghai East Hospital ( Site 2403)
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital affiliated to Fudan University ( Site 2407)
state: Shanghai
city: XiAn
country: China
facility: 1st Affil hosp of Med College of Xi'an Jiaotong University ( Site 2428)
state: Shanxi
city: Urumqi
country: China
facility: Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2420)
state: Xinjiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital ( Site 2446)
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Show Hospital ( Site 2427)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 2417)
state: Zhejiang
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: