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

Official title

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• R0 Resection Rate [Time frame: From treatment initiation to pathological assessment after radical surgery, up to approximately 28 weeks]

Secondary outcome measures (6)

• Conversion Surgery Rate [Time frame: From treatment initiation to radical surgery, up to approximately 24 weeks]
• Event-Free Survival [Time frame: From treatment initiation to disease progression, recurrence, or death from any cause, assessed up to approximately 32 months]
• Objective Response Rate [Time frame: From baseline to preoperative tumor assessment after completion of preoperative conversion therapy, up to approximately 20 weeks]
• Overall Survival [Time frame: From treatment initiation to death from any cause, assessed up to approximately 32 months]
• Incidence of Treatment-Related Adverse Events [Time frame: From treatment initiation to 30 days after the last dose of study treatment]
• Incidence of Perioperative Complications [Time frame: From radical surgery to 30 days after radical surgery]

Eligibility criteria

Inclusion criteria

• Histologically confirmed gastric or gastroesophageal junction adenocarcinoma by gastroscopic biopsy.
• 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.
• HER2-low, HER2-intermediate, or HER2-negative disease, and PD-L1 CPS ≥1.
• Age 18 to 75 years.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• No prior systemic therapy for advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
• 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.
• 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.
• Good compliance and willingness to complete study follow-up.

Exclusion criteria

• History of malignancy within 5 years or current presence of another malignancy.
• Prior systemic therapy for advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
• Macroscopically visible peritoneal metastasis or other unresectable distant metastasis.
• Active bleeding from the tumor as shown by endoscopy.
• 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.
• 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.
• Any active infection requiring systemic anti-infective therapy within 14 days before the first dose, except prophylactic antibiotics.
• 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.
• 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.
• New York Heart Association class III or IV heart failure or left ventricular ejection fraction <50% by echocardiography.
• Known hypersensitivity to SHR-1701 or active ingredients or excipients of the chemotherapy drugs used in this study.
• Known history of human immunodeficiency virus infection.
• Untreated active hepatitis B, defined as HBsAg positivity with HBV DNA above the upper limit of normal at the study site.
• Receipt of a live vaccine within 30 days before the first dose.
• Active pulmonary tuberculosis.
• Clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction.
• Liver disease such as cirrhosis, decompensated liver disease, or acute or chronic active hepatitis.
• Poorly controlled diabetes mellitus, defined as fasting blood glucose >10 mmol/L.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07709767 · K202606-54

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗