Pembrolizumab/placebo plus chemotherapy as first-line therapy in participants with HER2 negative advanced gastric or GEJ adenocarcinoma
- Conditions
- Gastric and gastric esophageal junction (GEJ) adenocarcinoma
- Registration Number
- 2023-508890-10-00
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
1. To compare the overall survival (OS) of the participants following administration of pembrolizumab versus placebo when each is combined with chemotherapy
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ended
- Sex
- Not specified
- Target Recruitment
- 268
Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with known PD-L1 expression status
Has adequate organ function as demonstrated by laboratory testing within 10 days prior to the start of study treatment
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 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 squamous cell or undifferentiated gastric cancer
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 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 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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method OS in All Participants OS in All Participants
OS In Participants With PD-L1 CPS ≥1 OS In Participants With PD-L1 CPS ≥1
OS In Participants With PD-L1 CPS ≥10 OS In Participants With PD-L1 CPS ≥10
- Secondary Outcome Measures
Name Time Method DOR Per RECIST 1.1 Assessed by BICR In Participants With PD-L1 CPS ≥10 DOR Per RECIST 1.1 Assessed by BICR In Participants With PD-L1 CPS ≥10
Number of Participants Who Experienced an Adverse Event (AE) Number of Participants Who Experienced an Adverse Event (AE)
ORR Per RECIST 1.1 Assessed by BICR in All Participants ORR Per RECIST 1.1 Assessed by BICR in All Participants
PFS Per RECIST 1.1 Assessed by BICR in All Participants PFS Per RECIST 1.1 Assessed by BICR in All Participants
PFS Per RECIST 1.1 Assessed by BICR In Participants With PD-L1 CPS ≥1 PFS Per RECIST 1.1 Assessed by BICR In Participants With PD-L1 CPS ≥1
PFS Per RECIST 1.1 Assessed by BICR In Participants With PD-L1 CPS ≥10 PFS Per RECIST 1.1 Assessed by BICR In Participants With PD-L1 CPS ≥10
ORR Per RECIST 1.1 Assessed by BICR in Participants With PD-L1 CPS ≥1 ORR Per RECIST 1.1 Assessed by BICR in Participants With PD-L1 CPS ≥1
ORR Per RECIST 1.1 Assessed by BICR in Participants With PD-L1 CPS ≥10 ORR Per RECIST 1.1 Assessed by BICR in Participants With PD-L1 CPS ≥10
DOR Per RECIST 1.1 Assessed by BICR in All Participants DOR Per RECIST 1.1 Assessed by BICR in All Participants
DOR Per RECIST 1.1 Assessed by BICR In Participants With PD-L1 CPS ≥1 DOR Per RECIST 1.1 Assessed by BICR In Participants With PD-L1 CPS ≥1
Number of Participants Who Discontinued Study Treatment Due To an AE Number of Participants Who Discontinued Study Treatment Due To an AE
Trial Locations
- Locations (24)
Istituto Oncologico Veneto
🇮🇹Padova, Italy
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Odense University Hospital
🇩🇰Odense C, Denmark
Rigshospitalet
🇩🇰Copenhagen Oe, Denmark
Hospital Germans Trias I Pujol
🇪🇸Badalona, Spain
Hospital Universitario Marques De Valdecilla
🇪🇸Santander, Spain
Fakultni Nemocnice Plzen
🇨🇿Plzen 23, Czechia
Dolnoslaskie Centrum Onkologii Pulmonologii I Hematologii
🇵🇱Wroclaw, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
🇵🇱Cracow, Poland
Lux Med Onkologia Sp. z o.o.
🇵🇱Warsaw, Poland
Scroll for more (14 remaining)Istituto Oncologico Veneto🇮🇹Padova, ItalySara LonardiSite contact00390498215910sara.lonardi@iov.veneto.it