Resumen

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. The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS). Once a participant has achieved the study objective or the study has ended, the participant will be discontinued from this study and enrolled in an extension study (Keynote 587; NCT03486873) to continue protocol-defined assessments and treatment.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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 treatment period and through 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 through 180 days after the last dose of chemotherapy or through 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

Criterios de exclusión

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 24 hours for urine or within 72 hours for serum 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-programmed cell death (PD)-1, anti-PD-L1 or anti-programmed cell death ligand 2 (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)
Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization or has not recovered from all adverse events (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 non-central 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

Intervenciones

biological

Pembrolizumab

Administered as an IV infusion on Day 1 Q3W

drug

Cisplatin

Administered as an IV infusion on Day 1 Q3W

drug

5-fluorouracil

Administered as a continuous IV infusion on Days 1-5 Q3W

drug

oxaliplatin

Administered as an IV infusion on Day 1 Q3W

drug

capecitabine

Administered orally BID on Days 1 to 14 Q3W

drug

Placebo for Pembrolizumab

Administered as an IV infusion on Day 1 Q3W

Ubicaciones

Instituto Medico Alexander Fleming ( Site 0307)

Buenos Aires, Buenos Aires F.D., Argentina

Instituto de Investigaciones Metabolicas ( Site 0312)

Buenos Aires, Argentina

Fundacion Favaloro - Hospital Universitario ( Site 0302)

Buenos Aires, Argentina

Centro Oncologico Riojano Integral ( Site 0313)

La Rioja, Argentina

Instituto San Marcos ( Site 0311)

San Juan, Argentina

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

Cisplatin

5-fluorouracil

oxaliplatin

capecitabine

Placebo for Pembrolizumab

Ubicaciones

Instituto Medico Alexander Fleming ( Site 0307)

Instituto de Investigaciones Metabolicas ( Site 0312)

Fundacion Favaloro - Hospital Universitario ( Site 0302)

Centro Oncologico Riojano Integral ( Site 0313)

Instituto San Marcos ( Site 0311)

Patrocinadores