Clinical Trials List
Protocol NumberMK3475-063
Not yet recruiting
2016-12-15 - 2020-06-08
Phase III
Terminated3
Study ended1
ICD-10C16.0
Malignant neoplasm of cardia
A Phase III, Randomized, Open-label Clinical Trial of Pembrolizumab (MK-3475) versus Paclitaxel in Asian Subjects with Advanced Gastric or Gastroesophageal Junction Adenocarcinoma who Progressed after First-Line Therapy with Platinum and Fluoropyrimidine
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
-
Sponsor
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/04/01
Investigators and Locations
Co-Principal Investigator
- 劉建廷 Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
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
Audit
None
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
- Wei-Ching Lin Division of Radiology
The Actual Total Number of Participants Enrolled
3 Study ended
Condition/Disease
Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Objectives
In PD-L1 positive subjects with advanced gastric or GEJ adenocarcinoma who have
progressed on one previous line of therapy.
1.Primary Objective(s) & Hypothesis(es)
(1) Objective: To compare OS.
Hypothesis: Pembrolizumab prolongs OS compared to paclitaxel.
(2) Objective: To compare PFS per RECIST 1.1 by blinded central radiologists’ review.
Hypotheses: Pembrolizumab prolongs PFS per RECIST 1.1 by blinded central
radiologists’ review compared to paclitaxel.
The study is considered to have met its primary objective if pembrolizumab is superior to
paclitaxel either in OS (interim or final analysis) or in the final PFS analysis.
2 Secondary Objective(s) & Hypothesis(es)
(1) To evaluate the Objective Response Rate (ORR) per RECIST 1.1 assessed by blinded
central radiologists’ review.
Hypotheses: Pembrolizumab improves ORR per RECIST 1.1 assessed by blinded central
radiologists’ review compared to paclitaxel.
(2) Objective: Evaluate the safety and tolerability profile of pembrolizumab compared to
paclitaxel.
Test Drug
Keytruda
Active Ingredient
Dosage Form
Dosage
100mg/4mL
Endpoints
The primary efficacy endpoints are overall survival (OS) and progression-free survival
(PFS).
To evaluate the Objective Response Rate (ORR) per RECIST 1.1 assessed by blinded
central radiologists’ review.
(PFS).
To evaluate the Objective Response Rate (ORR) per RECIST 1.1 assessed by blinded
central radiologists’ review.
Inclution 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 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 histologically or cytologically-confirmed diagnosis of gastric or GEJ adenocarcinoma.
4. Have metastatic disease or locally advanced, unresectable disease.
5. Have measurable disease as defined by RECIST 1.1 as determined by investigator.
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.
6. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group
(ECOG) Performance Scale within 3 days prior to the first dose of study therapy.
7. Has experienced documented objective radiographic or clinical disease progression
during or after first-line therapy containing any platinum/fluoropyrimidine doublet.
a. To be considered as second-line, the subject needs to have the documentation of
disease progression on first-line treatment. The disease progression can be confirmed
by CT scan or by clinical evidence (such as cytology report from newly developed
ascites and plural effusion).
b. Any new or worsening malignant effusion (documented by ultrasound) may be
confirmed by pathologic criteria (histology and/or cytology) if appropriate.
c. A subject experiencing clinical disease progression during or within 6 months
following the last dose of adjuvant or neo-adjuvant therapy will be eligible for enrollment provided they received a platinum/fluoropyrimidine doublet as required.
d. To be eligible, the subject is required to have received at least one dose of platinum
and fluoropyrimidine therapy. The dose reduction and discontinuation of one of these
drugs, switching to/adding new drugs on the first-line treatment is allowed; however,
the documentation of disease progression on/after the first-line treatment is required.
Therefore, subjects with discontinuation due to adverse events on first-line treatment
prior to disease progression are not eligible until disease progression is confirmed by
documentation.
8. Be willing to provide tissue for PD-L1 biomarker analysis and, based on the adequacy of
the tissue sample quality for assessment of PD-L1 status, receives notification of
adequate sample from the core lab. Repeat samples may be required if adequate tissue is
not provided. Newly-obtained biopsy specimens are preferred to archived samples and
formalin-fixed, paraffin-embedded (FFPE) block specimens are preferred to slides.
a. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to
initiation of treatment on Day 1. Subjects for whom newly-obtained endoscopic samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
9. Have tumor express PD-L1 positive (based on analysis of sample provided to core lab).
10. Subjects must have HER-2/neu status of tumors determined. If HER2/neu negative,
subject will be eligible, if positive, subject must have documentation of disease progression on treatment containing trastuzumab.
Note: if in the opinion of the investigator that subject have been considered ineligible or
inaccessible to trastuzumab treatment, he/she may be enrolled after consultation with
the Sponsor.
11. 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 study through 120 days after the last dose of study treatment for the pembrolizumab
arm and through 180 days after the last dose of study treatment for the paclitaxel arm
(Reference 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.
Male subjects should agree to use an adequate method of contraception starting with the
first dose of study therapy through 120 days after the last dose of study treatment forthe pembrolizumab arm and through 180 days after the last dose of study treatment for
the paclitaxel arm.
12. Demonstrate adequate organ function as defined in . All screening labs should be
performed within 10 days of trail treatment initiation
13. 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 therapy. If the
urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be
required.
1. Be willing and able to provide written informed consent/assent for the trial. The subject
may also provide consent 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 histologically or cytologically-confirmed diagnosis of gastric or GEJ adenocarcinoma.
4. Have metastatic disease or locally advanced, unresectable disease.
5. Have measurable disease as defined by RECIST 1.1 as determined by investigator.
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.
6. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group
(ECOG) Performance Scale within 3 days prior to the first dose of study therapy.
7. Has experienced documented objective radiographic or clinical disease progression
during or after first-line therapy containing any platinum/fluoropyrimidine doublet.
a. To be considered as second-line, the subject needs to have the documentation of
disease progression on first-line treatment. The disease progression can be confirmed
by CT scan or by clinical evidence (such as cytology report from newly developed
ascites and plural effusion).
b. Any new or worsening malignant effusion (documented by ultrasound) may be
confirmed by pathologic criteria (histology and/or cytology) if appropriate.
c. A subject experiencing clinical disease progression during or within 6 months
following the last dose of adjuvant or neo-adjuvant therapy will be eligible for enrollment provided they received a platinum/fluoropyrimidine doublet as required.
d. To be eligible, the subject is required to have received at least one dose of platinum
and fluoropyrimidine therapy. The dose reduction and discontinuation of one of these
drugs, switching to/adding new drugs on the first-line treatment is allowed; however,
the documentation of disease progression on/after the first-line treatment is required.
Therefore, subjects with discontinuation due to adverse events on first-line treatment
prior to disease progression are not eligible until disease progression is confirmed by
documentation.
8. Be willing to provide tissue for PD-L1 biomarker analysis and, based on the adequacy of
the tissue sample quality for assessment of PD-L1 status, receives notification of
adequate sample from the core lab. Repeat samples may be required if adequate tissue is
not provided. Newly-obtained biopsy specimens are preferred to archived samples and
formalin-fixed, paraffin-embedded (FFPE) block specimens are preferred to slides.
a. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to
initiation of treatment on Day 1. Subjects for whom newly-obtained endoscopic samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
9. Have tumor express PD-L1 positive (based on analysis of sample provided to core lab).
10. Subjects must have HER-2/neu status of tumors determined. If HER2/neu negative,
subject will be eligible, if positive, subject must have documentation of disease progression on treatment containing trastuzumab.
Note: if in the opinion of the investigator that subject have been considered ineligible or
inaccessible to trastuzumab treatment, he/she may be enrolled after consultation with
the Sponsor.
11. 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 study through 120 days after the last dose of study treatment for the pembrolizumab
arm and through 180 days after the last dose of study treatment for the paclitaxel arm
(Reference 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.
Male subjects should agree to use an adequate method of contraception starting with the
first dose of study therapy through 120 days after the last dose of study treatment forthe pembrolizumab arm and through 180 days after the last dose of study treatment for
the paclitaxel arm.
12. Demonstrate adequate organ function as defined in . All screening labs should be
performed within 10 days of trail treatment initiation
13. 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 therapy. If the
urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be
required.
Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. Is currently participating and receiving study therapy or has participated in a study of
an investigational agent and received study therapy or used an investigation device
within 4 weeks of the first dose of treatment.
2. Has squamous cell or undifferentiated gastric cancer.
3. Has 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.
4. 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.
5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due
to agents administered more than 4 weeks earlier.
6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
baseline) from adverse events due to a previously administered agent. Note: Subjects
with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and
may qualify for the study.
a. If subject received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.
7. 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, or in situ cervical cancer that has undergone potentially curative therapy.
8. 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 for at least four weeks
prior to the first dose of trial treatment and any 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.
9. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
10. Has an active infection requiring systemic therapy.
11. 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.
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 120 days after
the last dose of study treatment for the pembrolizumab arm and through 180 days after
the last dose of study treatment for the paclitaxel arm.
14. Has received prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2
agent, or if the subject has previously participated in Merck pembrolizumab (MK-3475)
clinical trials.
15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
16. Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positive
HBsAg result and HBV viral load exceed 2000 IU/ml (104 copies/ml). Active Hepatitis
C is defined by a known positive Hep C Ab result and known quantitative HCV RNA
results greater than the lower limits of detection of the assay.
Note: testing for HCV RNA (quantitative), HBsAg will be performed at screening; if
results obtained within 3 months before screening are available, they can be used.
17. Has received a live vaccine within 30 days of planned start of study therapy.
a. Note: Seasonal influenza vaccines for injection are generally inactivated flu
vaccines and are allowed; however intranasal influenza vaccines (e.g., FluMist ®)
are live attenuated vaccines, and are not allowed.
18. Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy.
1. Is currently participating and receiving study therapy or has participated in a study of
an investigational agent and received study therapy or used an investigation device
within 4 weeks of the first dose of treatment.
2. Has squamous cell or undifferentiated gastric cancer.
3. Has 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.
4. 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.
5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due
to agents administered more than 4 weeks earlier.
6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
baseline) from adverse events due to a previously administered agent. Note: Subjects
with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and
may qualify for the study.
a. If subject received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.
7. 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, or in situ cervical cancer that has undergone potentially curative therapy.
8. 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 for at least four weeks
prior to the first dose of trial treatment and any 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.
9. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
10. Has an active infection requiring systemic therapy.
11. 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.
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 120 days after
the last dose of study treatment for the pembrolizumab arm and through 180 days after
the last dose of study treatment for the paclitaxel arm.
14. Has received prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2
agent, or if the subject has previously participated in Merck pembrolizumab (MK-3475)
clinical trials.
15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
16. Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positive
HBsAg result and HBV viral load exceed 2000 IU/ml (104 copies/ml). Active Hepatitis
C is defined by a known positive Hep C Ab result and known quantitative HCV RNA
results greater than the lower limits of detection of the assay.
Note: testing for HCV RNA (quantitative), HBsAg will be performed at screening; if
results obtained within 3 months before screening are available, they can be used.
17. Has received a live vaccine within 30 days of planned start of study therapy.
a. Note: Seasonal influenza vaccines for injection are generally inactivated flu
vaccines and are allowed; however intranasal influenza vaccines (e.g., FluMist ®)
are live attenuated vaccines, and are not allowed.
18. Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy.
The Estimated Number of Participants
-
Taiwan
22 participants
-
Global
360 participants
