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This study is an open-label, single arm, phase II trial the efficacy and safety of pembrolizumab + CapeOx (HER2 negative ARM) or pembrolizumab + Trastuzumab + Capecitabine/Cisplatin (HER2 positive ARM) as first line therapy in advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Cohort A is allocated for the patients with Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma who confirmed with HER2 negative, and approximately 78 subjects will be enrollment to evaluate the efficacy and safety of pembrolizumab + Capecitabine/oxaliplatin.
Cohort B is allocated for the patients with Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma who confirmed with HER2 positive, and approximately 15 subjects will be enrollment to evaluate the efficacy and safety of pembrolizumab + Trastuzumab + Capecitabine/Cisplatin
(1 Cycle: Day 1 through Day 21)
Planned Biopsy Analysis immediate pre-treatment biopsy before chemotherapy; Newly-obtained specimens are defined as FFPE-preserved blocks or fresh tissue collected up to 12 weeks prior to C1D1.
2.on treatment primary tumor biopsy (C2D1 - 3 days window; before administration of C2D1) to explore whether tumor has change in characters (i.e., immune desert to immune infiltration) 3.on treatment primary tumor biopsy (C7D1 - 3 days window; before administration of C7D1) to explore whether tumor has change in characters (i.e., immune desert to immune infiltration) 4.At progression biopsy will be optional whenever the tumor biopsy is feasible.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CapeOx+Pembrolizumab(HER2 negative) | Experimental | <Cohort A>: HER2 negative patients CapeOx+Pembrolizumab therapy (N=78)
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| Cape/Cis+Trastuzumab+Pembrolizumab (HER2 positive ) | Experimental | Cape/Cis+Trastuzumab+Pembrolizumab therapy (N=15)
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Drug | Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Keytruda ™ (pembrolizumab) has recently been approved in the United Stated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. |
| Measure | Description | Time Frame |
|---|---|---|
| ORR (objective response rate) per RECIST 1.1 | Git is recommended that the subject bediscontinued from the study treatment unless, in the Investigator's opinion, the subject is deriving benefit from treatment. | 24months |
| Measure | Description | Time Frame |
|---|---|---|
| Genomic analysis | Whole Exome Sequencing at baseline, RNA-seq pre and post | 24months |
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Inclusion Criteria:
111.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 medication . Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
12.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 therapy.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Samsung Medical Center | Seoul | 99999 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41027671 | Derived | Lim SH, Kuwata T, An M, Hong JY, Kim ST, Matsubara Y, Shitara K, Lee J. Dynamic modulation of claudin18.2 expression and remodeling of the tumor microenvironment in gastric cancer during chemo-immunotherapy. J Immunother Cancer. 2025 Sep 29;13(9):e012683. doi: 10.1136/jitc-2025-012683. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | May 21, 2024 | |
| Reset | Sep 19, 2024 | |
| Release | May 11, 2026 | |
| Reset | Jun 4, 2026 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| May 21, 2024 | Sep 19, 2024 | |||
| May 11, 2026 |
| ID | Term |
|---|---|
| D013274 | Stomach Neoplasms |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
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Assigned to 1 group according to the result of HER2. <Cohort A>: HER2 negative patients CapeOx+Pembrolizumab therapy (N=78)
Cycle 1 CapeOX
Cycle 2 up to Cycle 8 CapeOX + pembrolizumab therapy
Cycle 9 up to Cycle 35 Capecitabine + pembrolizumab therapy
CapeOx + Pembrolizumab administered until disease progression, unacceptable toxicity or patient's refusal.
<Cohort B>: HER2 positive patients Cape/Cis+Trastuzumab+Pembrolizumab therapy (N=15)
Cycle 1 Capecitabine + cisplatin (Cape/Cis)
Cycle 2 up to Cycle 8 Cape/Cis + Trastuzumab + pembrolizumab therapy
Cycle 9 up to Cycle 35 Capecitabine + Trastuzumab + pembrolizumab therapy
Cape/Cis + Trastuzumab + Pembrolizumab administered until disease progression, unacceptable toxicity or patient's refusal.
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| Jun 4, 2026 |
| D004066 |
| Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |