Conversion Therapy With Retlirafusp Alfa Plus Chemotherapy in Gastric or Gastroesophageal Junction Adenocarcinoma

A Single-Arm, Exploratory Study of Retlirafusp Alfa Plus Chemotherapy as Conversion Therapy for Gastric or Gastroesophageal Junction Adenocarcinoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Retlirafusp Alfa; Drug: Oxaliplatin; Drug: Capecitabine; Procedure: Radical Surgery

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed gastric or gastroesophageal junction adenocarcinoma by gastroscopic biopsy.
2. Potentially resectable gastric or gastroesophageal junction adenocarcinoma as judged by the investigator, including but not limited to: T4b disease or fixed/fused lymph nodes; single liver metastasis, limited para-aortic lymph node metastasis (No.16a2/b1), or CY1P0 disease; more than one liver metastasis or a liver metastasis larger than 5 cm adjacent to the hepatic vein or portal vein, extensive para-aortic lymph node metastasis (No.16a1/b2), or selected distant metastases such as Virchow lymph node or lung metastasis.
3. HER2-low, HER2-intermediate, or HER2-negative disease, and PD-L1 CPS ≥1.
4. Age 18 to 75 years.
5. Eastern Cooperative Oncology Group performance status of 0 or 1.
6. No prior systemic therapy for advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
7. Adequate organ function, defined as: white blood cell count ≥3.0 × 10^9/L; absolute neutrophil count ≥1.5 × 10^9/L; platelet count ≥100 × 10^9/L; total bilirubin ≤ upper limit of normal; AST and ALT ≤3 × upper limit of normal; serum creatinine ≤1.5 × upper limit of normal or creatinine clearance ≥50 mL/min; activated partial thromboplastin time and international normalized ratio ≤1.5 × upper limit of normal; cardiac enzymes within normal range; and normal thyroid function. Participants with abnormal baseline TSH may be eligible if total T3 or free T3 and free T4 are within the normal range.
8. Female participants of childbearing potential must have a negative serum pregnancy test within 72 hours before the first dose and agree to use effective contraception during the study and for at least 3 months after the last dose. Male participants with partners of childbearing potential must be surgically sterilized or agree to use effective contraception during the study and for at least 3 months after the last dose.
9. Good compliance and willingness to complete study follow-up.

Exclusion Criteria:

1. History of malignancy within 5 years or current presence of another malignancy.
2. Prior systemic therapy for advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
3. Macroscopically visible peritoneal metastasis or other unresectable distant metastasis.
4. Active bleeding from the tumor as shown by endoscopy.
5. Use of traditional Chinese medicine with antitumor indication or systemic immunomodulatory drugs, including thymosin, interferon, or interleukin, within 2 weeks before the first dose, except for local use to control pleural effusion.
6. Requirement for systemic corticosteroids equivalent to prednisone >10 mg/day or other immunosuppressive therapy within 14 days before the first dose or during the study, except for topical or inhaled corticosteroids or adrenal replacement therapy at a dose equivalent to prednisone ≤10 mg/day in the absence of active autoimmune disease.
7. Any active infection requiring systemic anti-infective therapy within 14 days before the first dose, except prophylactic antibiotics.
8. Thrombotic events within 6 months before screening, including cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or pulmonary embolism, except catheter-related venous thrombosis that has resolved as judged by the investigator.
9. Myocardial infarction or poorly controlled arrhythmia within 6 months before the first dose, including QTc interval ≥450 ms in males or ≥470 ms in females using Fridericia's formula.
10. New York Heart Association class III or IV heart failure or left ventricular ejection fraction <50% by echocardiography.
11. Known hypersensitivity to SHR-1701 or active ingredients or excipients of the chemotherapy drugs used in this study.
12. Known history of human immunodeficiency virus infection.
13. Untreated active hepatitis B, defined as HBsAg positivity with HBV DNA above the upper limit of normal at the study site.
14. Receipt of a live vaccine within 30 days before the first dose.
15. Active pulmonary tuberculosis.
16. Clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction.
17. Liver disease such as cirrhosis, decompensated liver disease, or acute or chronic active hepatitis.
18. Poorly controlled diabetes mellitus, defined as fasting blood glucose >10 mmol/L.
19. Any medical history, disease, treatment, laboratory abnormality, or other condition that may interfere with study results, prevent full participation in the study, or pose additional risk as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Retlirafusp Alfa Plus CAPOX

Drug: Retlirafusp Alfa; 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.; Drug: Oxaliplatin; Oxaliplatin 130 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.; Drug: Capecitabine; Capecitabine 1000 mg/m^2 will be administered orally twice daily on Days 1-14 of each 21-day cycle. Interventi; Procedure: Radical Surgery; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Tang-Du Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 30, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): August 30, 2032

Study Registration Dates

• First Submitted: July 9, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Gastric Cancer; SHR-1701; CAPOX; Conversion Therapy; Gastroesophageal Junction Adenocarcinoma; R0 Resection; Retlirafusp Alfa
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin
• Other Study ID Numbers: K202606-54

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No