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KEYNOTE-859: 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 or gastroesophageal junction (GEJ) adenocarcinoma

Description

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 participants.

Status

Accepting new patients

Primary Study Objective(s)

The primary objectives overall survival (OS) and progression-free survival (PFS).

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma with known programmed cell death ligand 1 (PD-L1) expression status
  • Have a HER2 negative cancer
  • If male, agrees to use contraception during the treatment period and through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater, and must refrain from donating sperm during this period
  • If female, is not pregnant, not breastfeeding, and to whom at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP); or agrees to use contraception during the treatment period and through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater
  • Have measurable disease per RECIST 1.1 as assessed by investigator assessment
  • Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
  • Have provided tumor tissue sample deemed adequate for PD-L1 biomarker analysis
  • Have provided tumor tissue sample for microsatellite instability (MSI) biomarker analysis
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within three days prior to the start of study intervention
  • Have adequate organ function as demonstrated by laboratory testing within 10 days prior to the start of study treatment

Excluding patients who:

  • Have squamous cell or undifferentiated gastric cancer
  • Have 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
  • Have pre-existing peripheral neuropathy more than grade 1
  • Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation
  • Have had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant or adjuvant therapy as long as it was completed six months or less prior to randomization
  • Have 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 co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
  • Have received prior systemic anticancer therapy including investigational agents within four weeks prior to randomization or has not recovered from all AEs due to any previous therapies to grade 1 or less or baseline
  • Have received prior radiotherapy within two weeks prior to study start or has not recovered from all previous radiation-related toxicities, required corticosteroids, and have not had radiation pneumonitis. A one-week washout is permitted for palliative radiation (two weeks or less of radiotherapy) to non-central nervous system (CNS) disease
  • Have received a live 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 four weeks prior to the first dose of study treatment
  • Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within seven days prior to the first dose of study treatment
  • Have a known additional malignancy that is progressing or has required active treatment within the past five 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
  • Have known active CNS metastases and/or carcinomatous meningitis
  • Have severe hypersensitivity (grade 3 or more) to pembrolizumab and/or any of its excipients
  • Have an active autoimmune disease that has required systemic treatment in past two years
  • Have a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Have an active infection requiring systemic therapy
  • Have a known history of human immunodeficiency virus (HIV) infection
  • Have 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
  • Have a known history of active tuberculosis
  • Have hypokalemia (serum potassium less than the lower limit of normal)
  • Have hypomagnesemia (serum magnesium less than the lower limit of normal)
  • Have hypocalcemia (serum calcium less than the lower limit of normal)
  • Have a history or current evidence of any condition, (for example: 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
  • Have 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 greater
  • Have had an allogenic tissue/solid organ transplant
  • Have a known severe hypersensitivity (grade 3 or more) 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
  • If taking Cisplatin, has grade 2 or less audiometric hearing loss (25 decibels in two consecutive wave ranges)
     

Accepting new patients

 

Learn more at

clinicaltrials.gov

 

Principal Investigator(s)

Arturo Loaiza-Bonilla