Clinical Trials List
Protocol NumberMK3475-585
NCT Number(ClinicalTrials.gov Identfier)NCT03221426
2018-04-19 - 2023-12-31
Phase III
Terminated7
ICD-10C16
Malignant neoplasm of stomach
ICD-9151.0
Malignant neoplasm of cardia of stomach
A Phase III, Randomized, Double-Blind, Clinical Trial of Pembrolizumab (MK-3475) Plus Chemotherapy (XP or FP) Versus Placebo Plus Chemotherapy (XP or FP) as Neoadjuvant/Adjuvant Treatment for Subjects With Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma (KEYNOTE-585)
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jen-Shi Chen 無
- Yung-Chia Kao 無
- Tai-Sen Yeh 無
- Wen-Chi Chou 無
- 徐潤德 無
- 洪建福 無
- 劉耿豪 無
- 曾振輝 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Yan-Shen Shan Division of General Surgery
- 趙盈瑞 Division of General Surgery
- Chien-Jui Huang 無
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Tsu-Yi Chao Division of Hematology & Oncology
- YEN-HAO SU Division of General Surgery
- Yao-Yu Hsieh Division of Hematology & Oncology
- Wei-Hong Cheng Division of Hematology & Oncology
- 蘇勇誠 Division of Hematology & Oncology
- Huey-En Tzeng Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Ann-Lii Cheng Division of General Surgery
- 楊博仁 Division of General Surgery
- 張端瑩 Division of General Surgery
- 梁逸歆 Division of General Surgery
- 陳炯年 Division of General Surgery
- Chih-Hung Hsu Division of General Surgery
- TA-CHEN HUANG Division of General Surgery
- MING-TSAN LIN Division of General Surgery
- I-RUE LAI Division of General Surgery
- Chiun Hsu Division of General Surgery
- 呂理駿 Division of General Surgery
- Hsiang-Fong Kao Division of Hematology & Oncology
- 李柏居 Division of General Surgery
- 林宗哲 Division of General Surgery
- 陳國興 Division of General Surgery
- 林育麟 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma
Objectives
1. Primary Objective(s) & Hypothesis(es)
(1) Objective: To evaluate overall survival.
Hypothesis: Pembrolizumab plus chemotherapy is superior to placebo
plus chemotherapy in terms of overall survival (OS).
(2) Objective: To evaluate event-free survival (EFS)
Hypothesis: Pembrolizumab plus chemotherapy is superior to placebo
plus chemotherapy in terms of EFS based on RECIST 1.1 as assessed by a blinded independent central review (BICR). Refer to Section 8.4, for the
Analysis Endpoints.
(3) Objective: To evaluate the rate of pathological complete response based
on central review. Pathological complete response (pathCR) is defined
as no invasive disease within an entirely submitted and evaluated gross
lesion, and histologically negative nodes.
Hypothesis: Pembrolizumab plus chemotherapy is superior to placebo
plus chemotherapy in terms of rate of pathCR at the time of surgery.
The pathCR rate is considered as an early endpoint. The study is
considered to have met its primary objective if pembrolizumab plus
chemotherapy is superior to placebo plus chemotherapy in OS or EFS.
2. Secondary Objective(s) & Hypothesis(es)
(1) Objective: To evaluate the safety and tolerability of pembrolizumab in
combination with chemotherapy.
(2) Objective: To evaluate the disease-free survival (DFS) as assessed by
BICR for subjects who are disease free after surgery.
Test Drug
KEYTRUDA
Active Ingredient
Humanized anti-PD-1 mAb
Dosage Form
Injection
Dosage
100 mg/ 4 mL/ vial
Endpoints
Primary
1. Overall Survival (OS) is defined as the time from randomization to death due to any cause. Subjects without documented death at the time of
analysis will be censored at the date of last known contact.
2. Event-free survival (EFS) will be assessed by blinded independent central
review.
EFS is defined as the time from randomization to the first of the following
events:
Radiographic disease progression per RECIST 1.1
Local or distant recurrence as assessed by CT scan or biopsy if
indicated (for subjects who are disease free after surgery);
Death due to any cause.
The second primary malignancy is not considered as an EFS event.
See Section 8.6.1 for the definition of censoring
3. Pathological Complete Response (pathCR) Rate: pathCR rate is defined as
the proportion of subjects having pathCR. Pathologic complete response
(pathCR) is defined as no invasive disease within an entirely submitted
and evaluated gross lesion, and histologically negative nodes.
Secondary
Disease-free Survival (DFS) is defined as the time from post-surgery baseline
scan until the first occurrence of:
local or distant recurrence;
death from any cause.
1. Overall Survival (OS) is defined as the time from randomization to death due to any cause. Subjects without documented death at the time of
analysis will be censored at the date of last known contact.
2. Event-free survival (EFS) will be assessed by blinded independent central
review.
EFS is defined as the time from randomization to the first of the following
events:
Radiographic disease progression per RECIST 1.1
Local or distant recurrence as assessed by CT scan or biopsy if
indicated (for subjects who are disease free after surgery);
Death due to any cause.
The second primary malignancy is not considered as an EFS event.
See Section 8.6.1 for the definition of censoring
3. Pathological Complete Response (pathCR) Rate: pathCR rate is defined as
the proportion of subjects having pathCR. Pathologic complete response
(pathCR) is defined as no invasive disease within an entirely submitted
and evaluated gross lesion, and histologically negative nodes.
Secondary
Disease-free Survival (DFS) is defined as the time from post-surgery baseline
scan until the first occurrence of:
local or distant recurrence;
death from any cause.
Inclution Criteria
1. Have previously untreated localized gastric or GEJ (Stage III or IVa)
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 subjects 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. Plan to proceed to surgery following pre-operative chemotherapy based
on standard staging studies per local practice.
3. Be at least 18 years of age on the day of signing informed consent.
(Subject in Taiwan aged at least 20 years)
4. Be willing to provide tissue from a tumor lesion at baseline and at time
of surgery.
5. Have an ECOG performance status of 0 to 1, to be performed within 3
days prior to the first dose of trial treatment.
6. 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.
7. Have adequate organ function as defined in the following table (Table 1).
Specimens must be collected within 10 days prior to the start of trial
treatment
8. Female subjects of childbearing potential must have a negative urine or
serum pregnancy test within72 hours prior to receiving the first dose of
trial medication. If the urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required.
9. All subjects of childbearing potential must be willing to use an adequate
method of contraception, as outlined in Section 5.7.2 - Contraception,
for the course of the trial through 120 days after the last dose of trial
drug.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
10. Life expectancy of greater than 6 months.
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 subjects 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. Plan to proceed to surgery following pre-operative chemotherapy based
on standard staging studies per local practice.
3. Be at least 18 years of age on the day of signing informed consent.
(Subject in Taiwan aged at least 20 years)
4. Be willing to provide tissue from a tumor lesion at baseline and at time
of surgery.
5. Have an ECOG performance status of 0 to 1, to be performed within 3
days prior to the first dose of trial treatment.
6. 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.
7. Have adequate organ function as defined in the following table (Table 1).
Specimens must be collected within 10 days prior to the start of trial
treatment
8. Female subjects of childbearing potential must have a negative urine or
serum pregnancy test within72 hours prior to receiving the first dose of
trial medication. If the urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required.
9. All subjects of childbearing potential must be willing to use an adequate
method of contraception, as outlined in Section 5.7.2 - Contraception,
for the course of the trial through 120 days after the last dose of trial
drug.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
10. Life expectancy of greater than 6 months.
Exclusion Criteria
1. Has a history of (non-infectious) pneumonitis that required steroids or
has current pneumonitis.
2. Has an active infection requiring systemic therapy.
3. Is currently participating in or has participated in a trial of an
investigational agent or has used an investigational device within 4
weeks prior to the first dose of trial treatment.
Note: Subjects who have entered the follow-up phase of an investigational
trial may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent.
4. 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 (i.e., CTLA-4, OX-40, CD137) or has previously
participated in a Merck pembrolizumab (MK-3475) clinical trial.
5. Has received prior systemic anti-cancer therapy including investigational
agents for the current malignancy.
Note: Subjects must have recovered from all AEs due to previous therapies
to ≤Grade 1 or baseline. Subjects with ≤Grade 2 neuropathy may be
eligible
Note: If subject received major surgery, they must have recovered
adequately from the toxicity and or complications from the intervention
prior to starting trial treatment.
6. Has received prior radiotherapy within 2 weeks of start of trial treatment
for any other condition. Subjects must have recovered from all
radiation-related toxicities, not require corticosteroids, and not have had
radiation pneumonitis.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy (in dosing exceeding 10 mg daily of prednisone
equivalent) or any other form of immunosuppressive therapy within 7
days prior the first dose of trial drug.
8. Has a known additional malignancy that is progressing or has required
active treatment within the past 5 years.
Note: Subjects with basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical
cancer in situ) that have undergone potentially curative therapy are not
excluded.
9. Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its
active substance and/or any of its excipients. (Refer to the respective
Investigator’s Brochure for a list of excipients.)
10. Has a known severe hypersensitivity (≥ Grade 3) to any of the study
chemotherapy agents and/or to any of their excipients.
11. 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) is not considered a form of systemic treatment
and is allowed.
12. Has a known history of human immunodeficiency virus (HIV) infection.
No HIV testing is required unless mandated by local health authority.
13. 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.
Note: No testing for Hepatitis B and Hepatitis C is required unless
mandated by local health authority.
14. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
15. Is pregnant or breastfeeding or expecting to conceive or father children
within the projected duration of the trial, starting with the screening visit
through 120 days after the last dose of trial treatment.
16. Has received a live vaccine within 30 days prior to the first dose of trial
drug. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, varicella/zoster (chicken pox),
yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid
vaccine. Seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; however, intranasal influenza vaccines
(e.g., FluMist®
) are live attenuated vaccines and are not allowed.
17. Has a history or current evidence of any condition, 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.
18. Has known psychiatric or substance abuse disorders that would interfere
with cooperating with the requirements of the trial.
has current pneumonitis.
2. Has an active infection requiring systemic therapy.
3. Is currently participating in or has participated in a trial of an
investigational agent or has used an investigational device within 4
weeks prior to the first dose of trial treatment.
Note: Subjects who have entered the follow-up phase of an investigational
trial may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent.
4. 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 (i.e., CTLA-4, OX-40, CD137) or has previously
participated in a Merck pembrolizumab (MK-3475) clinical trial.
5. Has received prior systemic anti-cancer therapy including investigational
agents for the current malignancy.
Note: Subjects must have recovered from all AEs due to previous therapies
to ≤Grade 1 or baseline. Subjects with ≤Grade 2 neuropathy may be
eligible
Note: If subject received major surgery, they must have recovered
adequately from the toxicity and or complications from the intervention
prior to starting trial treatment.
6. Has received prior radiotherapy within 2 weeks of start of trial treatment
for any other condition. Subjects must have recovered from all
radiation-related toxicities, not require corticosteroids, and not have had
radiation pneumonitis.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy (in dosing exceeding 10 mg daily of prednisone
equivalent) or any other form of immunosuppressive therapy within 7
days prior the first dose of trial drug.
8. Has a known additional malignancy that is progressing or has required
active treatment within the past 5 years.
Note: Subjects with basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical
cancer in situ) that have undergone potentially curative therapy are not
excluded.
9. Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its
active substance and/or any of its excipients. (Refer to the respective
Investigator’s Brochure for a list of excipients.)
10. Has a known severe hypersensitivity (≥ Grade 3) to any of the study
chemotherapy agents and/or to any of their excipients.
11. 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) is not considered a form of systemic treatment
and is allowed.
12. Has a known history of human immunodeficiency virus (HIV) infection.
No HIV testing is required unless mandated by local health authority.
13. 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.
Note: No testing for Hepatitis B and Hepatitis C is required unless
mandated by local health authority.
14. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
15. Is pregnant or breastfeeding or expecting to conceive or father children
within the projected duration of the trial, starting with the screening visit
through 120 days after the last dose of trial treatment.
16. Has received a live vaccine within 30 days prior to the first dose of trial
drug. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, varicella/zoster (chicken pox),
yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid
vaccine. Seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; however, intranasal influenza vaccines
(e.g., FluMist®
) are live attenuated vaccines and are not allowed.
17. Has a history or current evidence of any condition, 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.
18. Has known psychiatric or substance abuse disorders that would interfere
with cooperating with the requirements of the trial.
The Estimated Number of Participants
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Taiwan
38 participants
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Global
800 participants
