A Phase III, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) (SCH-900475) plus Chemotherapy (XP or FP) versus Placebo plus Chemotherapy (XP or FP) as Neoadjuvant/Adjuvant Treatment for Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE-585)
- Conditions
- Gastric or Gastroesophageal Junction AdenocarcinomaMedDRA version: 21.0Level: LLTClassification code 10056267Term: Gastroesophageal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004408-76-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 860
1.Have previously untreated localized gastric or 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. Siewert type 2 or 3 tumors are eligible. Enrollment of participants with
Siewert type 1 tumors will be limited to those for whom the planned treatment is perioperative chemotherapy and resection.
Tumor staging prior to enrollment must consist of at least 1 imaging modality: computed tomography (CT) or magnetic resonance imaging (MRI).
2.Be at least 18 years of age on the day of signing informed consent
3.Have an ECOG performance status of 0 to 1, to be performed within 3 days prior to the first dose of study treatment
4.Have a life expectancy of greater than 6 months
5.Male participants of childbearing potential must agree to use an adequate method of contraception as outlined in Appendix 3, for the course of the study through 180 days after the last dose of chemotherapy.
6.Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first
dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
7.Female participants of childbearing potential must be willing to use an adequate method of contraception as outlined in Appendix 3, 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.
8.The participant provides written informed consent for the study. The participant may also provide consent for Future Biomedical Research.
However, the participant may participate in the main study without participating in Future Biomedical Research.
9.Plan to proceed to surgery following pre operative chemotherapy based on standard staging studies per local practice.
10.Be willing to provide tissue from a tumor lesion at baseline and at time of surgery
11.Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 430
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 430
1.Has a history of (non infectious) pneumonitis that required steroids or has current pneumonitis
2.Has an active infection requiring systemic therapy
3.Has a diagnosis of immunodeficiency
4.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
5.Has a known severe hypersensitivity (= Grade 3) to pembrolizumab, its active substance and/or any of its excipients. (Refer to
the respective IB for a list of excipients.)
6.Has a known severe hypersensitivity (= Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.
7.Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying
agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemictreatment and is allowed.
8.Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local
health authority.
9.Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus
(defined as
HCV RNA [qualitative] is detected) infection.
10.Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
11.Female participants: Is pregnant or breastfeeding or expecting to conceive 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.
Male participants: Is 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.
12.Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase [DPD]), 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.
13.Has had an allogenic tissue/solid organ transplant.
14.Has known psychiatric or substance abuse disorder that would interfere with the partecipant's ability to cooperate with the requirements of the study.
15.A woman of child-bearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to receiving first
dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
16.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
co-inhibitory T-cell receptor (ie, CTLA-4, OX-40, CD137) or has previously participated in a Merck pembrolizumab (MK 3475) clinical study.
17.Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy.
18.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 to the first dose of
study treatment.
19.Has received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are
not limited to, the following: meas
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method