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Clinical Trials List

Protocol NumberMK3475-062
NCT Number(ClinicalTrials.gov Identfier)NCT02494583

2015-09-01 - 2019-12-31

Phase III

Terminated4

ICD-10C16

Malignant neoplasm of stomach

ICD-9151.9

Malignant neoplasm of stomach, unspecified

A Randomized, Active-Controlled, Partially Blinded, Biomarker Select, Phase III Clinical Trial of Pembrolizumab as Monotherapy and in Combination with Cisplatin+5-Fluorouracil versus Placebo+Cisplatin+5-Fluorouracil as First-Line Treatment in Subjects with Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

  • Trial Applicant

    Merck Sharp & Dohme (I.A.) LLC

  • Sponsor

    Merck Sharp & Dohme Corp.

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator Yee Chao Division of Hematology & Oncology
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

Audit

None

Principal Investigator Chia-Jui Yen Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

Audit

None

Principal Investigator Jen-Shi Chen Division of Hematology & Oncology
Linkou Chang Gung Medical Foundation

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

8 Terminated

Audit

None

Principal Investigator Kun-Huei Yeh Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Terminated

Audit

None

Condition/Disease

Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Objectives

This is a study of pembrolizumab (MK-3475) as first-line treatment for participants with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Participants whose tumors express programmed death-ligand 1 (PD-L1) will be randomly assigned to one of the three treatment arms of the study: pembrolizumab as monotherapy [pembro mono], pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or capecitabine [pembro combo], or placebo plus SOC chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or capecitabine [SOC]. The primary study hypotheses are that pembrolizumab in combination with SOC chemotherapy is superior to SOC chemotherapy alone in terms of Progression-free Survival (PFS) and Overall Survival (OS) in participants with PD-L1 Combined Positive Score (CPS) ≥1, pembrolizumab in combination with SOC chemotherapy is superior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥10, pembrolizumab monotherapy is non-inferior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1, and pembrolizumab monotherapy is superior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1 and in participants with PD-L1 CPS ≥10.

Test Drug

Pembrolizumab (MK-3475)

Active Ingredient

Humanized anti-PD-1 mAb

Dosage Form

Injection

Dosage

100mg/4mL

Endpoints

Primary Outcome Measures :
1. Pembro Combo vs SOC: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With PD-L1 CPS ≥1 (All Participants) [ Time Frame: Up to approximately 36 months (through Interim Analysis cut-off date of 26-Sep-2018) ]
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Per protocol, PFS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record.

2. Pembro Combo vs SOC: Overall Survival (OS) in Participants With PD-L1 CPS ≥1 (All Participants) [ Time Frame: Up to approximately 42 months (through Final Analysis cut-off date of 26-Mar-2019) ]
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, OS was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record.

3. Pembro Combo vs SOC: OS in Participants With PD-L1 CPS ≥10 [ Time Frame: Up to approximately 42 months (through Final Analysis cut-off date of 26-Mar-2019) ]
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥10. Per protocol, OS was compared separately between CPS ≥10 participants of the pembro mono arm and SOC arm and is presented later in the record.

4. Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥1 (All Participants) [ Time Frame: Up to approximately 42 months (through Final Analysis cut-off date of 26-Mar-2019) ]
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, OS was compared separately between CPS ≥1 participants of the pembro combo arm and SOC arm and is presented earlier in the record.

5. Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥10 [ Time Frame: Up to approximately 42 months (through Final Analysis cut-off date of 26-Mar-2019) ]
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥10. Per protocol, OS was compared separately between CPS ≥10 participants of the pembro combo arm and SOC arm and is presented earlier in the record.

Inclution Criteria

Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. Be willing and able to provide written informed consent/assent
for the trial. The subject may also provide consent/assent for
Future Biomedical Research. However, the subject may
participate in the main trial without participating in Future
Biomedical Research.
2. Be ≥ 18 years of age on day of signing informed consent (or
acceptable age according to local regulations, whichever is
older).
3. Have a performance status of 0 or 1 on the Eastern Cooperative
Oncology Group (ECOG) Performance Scale.
4. Have histologically or cytologically confirmed diagnosis of
locally advanced or metastatic gastric or GEJ adenocarcinoma.
5. Be HER2/neu negative and PD-L1 positive.
6. Have measurable disease as defined by RECIST 1.1 as
determined by investigator assessment. Tumor lesions situated
in a previously irradiated area are considered measurable if
progression has been demonstrated in such lesions.
a. Note: The exact same image acquisition and
processing parameters should be used throughout the
study.
7. Have provided tumor tissue sample deemed adequate for PD-L1
biomarker analysis. Refer to protocol Section 7.1.1.2.1 for
details
a. Notification of eligibility must be received prior to
randomization.
b. Additional samples may be required if adequate tissue is
not provided.
8. Female subjects of childbearing potential should be willing to
use 2 methods of birth control or be surgically sterile, or abstain
from heterosexual activity for the course of the trial through 180
days after the last dose of study medication (Reference protocol
Section 5.7.2). Subjects of childbearing potential are those
who have not been surgically sterilized or have not been free
from menses for > 1 year.
a. Abstinence is acceptable if this is the established and
preferred contraception for the subject.
9. Male subjects should agree to use an adequate method of
contraception starting with the first dose of study therapy
through 180 days after the last dose of study therapy.
10. Demonstrate adequate organ function as defined in Table 1.
All screening labs should be performed within 10 days of
treatment initiation.
11. Female subjects of childbearing potential should 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.

Exclusion Criteria

Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the
subject:
1. Has squamous cell or undifferentiated gastric cancer.
2. Has had previous therapy for locally advanced or metastatic
gastric/GEJ cancer. Subjects may have received prior
neoadjuvant or adjuvant therapy as long as it was completed at
least 6 months prior to randomization.
3. Has had major surgery, open biopsy or significant traumatic
injury within 28 days prior to randomization, or anticipation of
the need for major surgery during the course of study treatment.
4. Has had radiotherapy within 14 days of randomization. Subjects
who received radiotherapy >14 days prior to randomization
must have completely recovered from any radiotherapy related
AEs/toxicities.
5. Has a known additional malignancy that is progressing or
requires active treatment. Exceptions include basal cell
carcinoma of the skin, squamous cell carcinoma of the skin that
has undergone potentially curative therapy or in situ cervical
cancer.
6. Has known active central nervous system (CNS) metastases
and/or carcinomatous meningitis. Subjects with previously
treated brain metastases may participate provided they are
stable (without evidence of progression by imaging at least four
weeks prior to the first dose of trial treatment and neurologic
symptoms have returned to baseline), have no evidence of new
or enlarging brain metastases, and are not using steroids for at
least 7 days prior to trial treatment. This exception does not
include carcinomatous meningitis which is excluded regardless
of clinical stability.
7. Has an active autoimmune disease that has required systemic
treatment in past 2 years (i.e. with use of disease modifying
agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic
treatment.
8. Has a diagnosis of immunodeficiency or is receiving systemic
steroid therapy or any other form of immunosuppressive
therapy within 7 days prior to the first dose of trial treatment.
The use of physiologic doses of corticosteroids may be
approved after consultation with the Sponsor.
9. Has history or evidence of interstitial lung disease or active,
non-infectious pneumonitis.
10. Has an active infection requiring systemic therapy
11. Has a history or current evidence of any condition (e.g. known
deficiency of the enzyme dihydropyrimidine dehydrogenase
[DPD]), therapy, or laboratory abnormality that might confound
the results of the trial, interfere with the subject’s participation
for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating
investigator.
12. Has known psychiatric or substance abuse disorders that would
interfere with cooperation with the requirements of the trial.
13. Is pregnant or breastfeeding, or expecting to conceive or father
children within the projected duration of the trial, starting with
the screening visit through 180 days after the last dose of trial
treatment.
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or
anti-PD-L2 agent.
15. Has a known history of Human Immunodeficiency Virus (HIV)
(HIV 1/2 antibodies).
16. Has known active Hepatitis B (e.g., HBsAg reactive) or
Hepatitis C (e.g., HCV RNA [qualitative] is detected).
17. Is currently participating in and receiving study therapy or has
participated in a study of an investigational agent and received
study therapy or used an investigational device within 4 weeks
prior to the first dose of trial treatment.
18. Has received a live vaccine within 30 days of planned start of
study therapy.
Note: Seasonal influenza vaccines for injection are
generally inactivated flu vaccines and are allowed; however
intranasal influenza vaccines (e.g., Flu-Mist®
) are live
attenuated vaccines, and are not allowed.
19 Is or has an immediate family member (e.g., spouse,
parent/legal guardian, sibling or child) who is investigational
site or sponsor staff directly involved with this trial, unless
prospective IRB approval (by chair or designee) is given
allowing exception to this criterion for a specific subject.

The Estimated Number of Participants

  • Taiwan

    17 participants

  • Global

    750 participants

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