A Clinical Study of Iparomlimab and Tuvonralimab Combined With SOX Following Heterogeneous Radiotherapy as First-line Treatment for Unresectable Locally Advanced or Metastatic HER2-negative Gastric or Gastroesophageal Junction Adenocarcinoma

NCT07502027 | Not Yet Recruiting Phase 4

• 1 other identifier: TJ-IRB202602008
• Study Type: interventional
• Target: 55
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a domestic, multicenter, single-arm clinical trial designed to evaluate the efficacy and safety of heterogeneous radiotherapy (high and low dose) sequenced with iparomlimab and tuvonralimab plus SOX as a first-line treatment for unresectable locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma.

Conditions

Gastric Cancer (Diagnosis); Gastric Cancer (GC); Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The proportion of subjects with a radiologically confirmed complete response (CR) or partial response (PR) to tumor, as assessed by the investigator based on the RECIST v1.1 criteria.

  1 year

Secondary Outcomes (2)

• Disease Control Rate (DCR)

  1 year

• Overall Survival (OS)

  From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Study Arms (1)

Immunotherapy Combined with SOX Chemotherapy Following Radiation Therapy

EXPERIMENTAL

Radiation Therapy Dosage and Subsequent Treatment Regimen The radiation therapy (RT) dosage is specified as follows: For the primary tumor or main recurrent lesion: Radiation therapy at 3 Gy per fraction (F), totaling 10 fractions, administered 5 days per week. For major metastatic lesions: Radiation therapy at 2 Gy per fraction (F), totaling 1 fraction. One week after the completion of radiation therapy, iparomlimab and tuvonralimab plus SOX chemotherapy will be initiated. The planned regimen is as follows: Iparomlimab and tuvonralimab: 5 mg/kg (dose for the combined immunotherapy). SOX chemotherapy: Oxaliplatin 130 mg/m² via intravenous infusion (iv) on Day 1 (d1) + Tegafur/Gimeracil/Oteracil Potassium 40-60 mg orally (po) twice daily (bid) from Day 1 to Day 14 (d1-14). Treatment cycle: 21 days per cycle.

Drug: Iparomlimab and Tuvonralimab (QL1706)

Interventions

Iparomlimab and Tuvonralimab (QL1706) DRUG

anti-PD-1/anti-CTLA-4 dual immunotherapy

Also known as: QL1706

Immunotherapy Combined with SOX Chemotherapy Following Radiation Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years, male or female.
• Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
• Patients with no prior systemic therapy for locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. For patients who received neoadjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent, the interval from the last treatment to disease progression must be at least 6 months.
• HER-2 negative (IHC 1+ or IHC 2+/FISH-negative).
• Presence of radiation-eligible tumor lesions.
• No anticipated need for tumor resection during the study treatment period.
• ECOG performance status 0-1.
• At least one measurable lesion per RECIST v1.1. Lesions that have received prior radiotherapy cannot be selected as target lesions unless they are the only measurable lesions and show unequivocal progression on imaging, in which case they may be considered as target lesions.
• Expected overall survival ≥ 3 months.
• Adequate function of major organs.

You may not qualify if:

• Presence of other histologic components confirmed by histopathology or cytology, such as squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine carcinoma, etc.
• Prior treatment with any tumor immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies), immune checkpoint agonists (e.g., antibodies targeting ICOS, CD40, CD137, GITR, OX40), or immune cell therapy (e.g., CAR-T cells).
• Palliative local therapy to non-target lesions within 2 weeks before the first dose; or systemic non-specific immunomodulatory therapy (e.g., interleukin, interferon, thymosin) within 2 weeks before the first dose.
• Clinically significant pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1 time per month).
• Known active or untreated brain metastasis, meningeal metastasis, spinal cord compression, or leptomeningeal disease. Patients with measurable lesions outside the central nervous system may be eligible if: they are asymptomatic after treatment, radiologically stable for at least 4 weeks before study treatment (no new or enlarging brain metastases), and have discontinued systemic corticosteroids and anticonvulsants for at least 2 weeks.
• Gastrointestinal perforation, gastrointestinal fistula, or intra-abdominal abscess within 6 months before the first dose.
• Clinically significant bleeding or definite bleeding diathesis within 6 months before the first dose, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, or vasculitis, excluding asymptomatic positive fecal occult blood.
• Arterial or venous thromboembolism within 6 months before the first dose, including cerebrovascular accident (transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, pulmonary embolism, etc. Superficial venous thrombosis is permitted.
• Clinically active hemoptysis or active diverticulitis.
• Major surgery other than for gastric cancer diagnosis within 28 days before the first dose, or anticipated major surgery during the study period.
• Severe infection (CTCAE grade \> 2) within 4 weeks before the first dose, such as severe pneumonia, bacteremia, infectious complications requiring hospitalization; active lung inflammation on baseline chest imaging; or signs/symptoms of infection or oral/intravenous antibiotic therapy within 14 days before the first dose, excluding prophylactic antibiotics.
• Any active or history of autoimmune disease, including but not limited to: interstitial lung disease, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism. Hypothyroidism may be allowed if controlled by hormone replacement. Patients with fully resolved psoriasis or childhood asthma/allergies requiring no intervention in adulthood may be included; those requiring medical intervention with bronchodilators are excluded.
• History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, organ transplantation, or allogeneic bone marrow transplantation.
• Uncontrolled cardiac conditions, including but not limited to:
• NYHA class ≥ II heart failure;

Sponsors & Collaborators

• Huazhong University of Science and Technology: lead

MeSH Terms

Conditions

Stomach Neoplasms; Disease

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 30, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share