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This is a prospective, single-arm, exploratory clinical study designed to evaluate the efficacy and safety of retlirafusp alfa plus CAPOX as conversion therapy in patients with potentially resectable gastric or gastroesophageal junction adenocarcinoma. Eligible participants will receive preoperative retlirafusp alfa in combination with capecitabine and oxaliplatin. Patients who achieve complete response or partial response and are considered suitable for R0 resection after multidisciplinary team assessment will undergo radical surgery. The primary outcome is R0 resection rate.
Eligible patients with potentially resectable gastric or gastroesophageal junction adenocarcinoma will receive retlirafusp alfa plus CAPOX every 3 weeks for 4 to 6 cycles before surgery. Tumor response will be assessed according to RECIST version 1.1. Patients with complete response or partial response who are considered suitable for R0 resection by a multidisciplinary team will undergo radical surgery 4 to 6 weeks after the last dose of preoperative treatment. Postoperative retlirafusp alfa maintenance therapy is recommended for up to 2 years. Patients who do not meet surgical criteria will receive subsequent treatment at the investigator's discretion. Efficacy outcomes include R0 resection rate, conversion surgery rate, event-free survival, objective response rate, and overall survival. Safety will be assessed according to CTCAE version 5.0 and perioperative complications will be graded using the Clavien-Dindo classification.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Retlirafusp Alfa Plus CAPOX | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Retlirafusp Alfa | Drug | Retlirafusp alfa 1800 mg will be administered by intravenous infusion on Day 1 of each 21-day cycle. When administered with chemotherapy, retlirafusp alfa will be given first, followed by chemotherapy after an interval of at least 30 minutes. |
| Measure | Description | Time Frame |
|---|---|---|
| R0 Resection Rate | The proportion of enrolled participants who undergo radical surgery with microscopically margin-negative resection. R0 resection will be assessed based on postoperative pathological evaluation. | From treatment initiation to pathological assessment after radical surgery, up to approximately 28 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Conversion Surgery Rate | The proportion of enrolled participants who undergo radical surgery after preoperative conversion therapy and multidisciplinary team assessment. | From treatment initiation to radical surgery, up to approximately 24 weeks |
| Event-Free Survival |
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Inclusion Criteria:
Exclusion Criteria:
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De-identified individual participant data will not be shared because this is a single-center investigator-initiated exploratory study, and the informed consent and data governance arrangements do not currently include a plan for sharing participant-level data with external researchers.
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| Oxaliplatin | Drug | Oxaliplatin 130 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle. |
|
| Capecitabine | Drug | Capecitabine 1000 mg/m^2 will be administered orally twice daily on Days 1-14 of each 21-day cycle. Interventi |
|
| Radical Surgery | Procedure | Participants who achieve complete response or partial response and are considered suitable for R0 resection after multidisciplinary team assessment will undergo radical surgery 4 to 6 weeks after the last dose of preoperative treatment. |
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Event-free survival is defined as the time from initiation of treatment to the first occurrence of radiographic disease progression according to RECIST version 1.1, tumor recurrence confirmed by imaging or biopsy, or death from any cause, whichever occurs first. |
| From treatment initiation to disease progression, recurrence, or death from any cause, assessed up to approximately 32 months |
| Objective Response Rate | Objective response rate is defined as the proportion of participants who achieve complete response or partial response according to RECIST version 1.1. | From baseline to preoperative tumor assessment after completion of preoperative conversion therapy, up to approximately 20 weeks |
| Overall Survival | Overall survival is defined as the time from treatment initiation to death from any cause. | From treatment initiation to death from any cause, assessed up to approximately 32 months |
| Incidence of Treatment-Related Adverse Events | Treatment-related adverse events, grade 3 or higher treatment-related adverse events, and immune-related adverse events will be assessed according to CTCAE version 5.0. | From treatment initiation to 30 days after the last dose of study treatment |
| Incidence of Perioperative Complications | Perioperative complications will be assessed using the Clavien-Dindo classification. | From radical surgery to 30 days after radical surgery |
| ID | Term |
|---|---|
| D013274 | Stomach Neoplasms |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
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| ID | Term |
|---|---|
| D000077150 | Oxaliplatin |
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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