A Prospective, Single-Center, Exploratory Phase II Clinical Study of Iparomlimab and Tuvonralimab (QL1706) Combined With Chemotherapy in the Treatment of Previously Untreated Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
The goal of this Phase II clinical trial is to evaluate the efficacy and safety of Iparomlimab and Tuvonralimab (QL1706) combined with SOX chemotherapy (S-1 plus Oxaliplatin) in patients with previously untreated advanced or metastatic gastric cancer or gastroesophageal junction cancer. The main questions it aims to answer are: 1、What is the objective response rate (ORR) of the combination of QL1706 and SOX chemotherapy? 2、What are the safety and tolerability of this combination therapy? Participants will: 1. Receive Iparomlimab and Tuvonralimab (QL1706) via intravenous infusion every 3 weeks. 2. Receive SOX chemotherapy (Oxaliplatin via intravenous infusion on Day 1 and S-1 orally twice daily for 14 days) every 3 weeks for up to 6 cycles. 3. Continue maintenance therapy with QL1706 combined with S-1 after 6 cycles until disease progression or unacceptable toxicity. 4. Undergo tumor imaging assessments (CT or MRI) every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter to monitor the disease.
• Voluntarily participate in the clinical study; fully understand and are informed about the study and sign the Informed Consent Form (ICF); willing to follow and able to complete all trial procedures.
• Age 18-80 years, gender is not limited.
• Patients with locally advanced unresectable, recurrent unresectable, or metastatic gastric cancer (GC) or gastroesophageal junction cancer (GEJC) confirmed by imaging and other examinations, and histopathologically confirmed as adenocarcinoma.
• Provide a report confirming HER2 overexpression or amplification negativity; defined as IHC 0/1+, or IHC 2+ with FISH/ISH negative.
• No prior systemic therapy for advanced or metastatic GC/GEJC (including anti-HER-2 therapy). Patients who have received adjuvant or neoadjuvant therapy (including chemotherapy, radiotherapy, or chemoradiotherapy) for GC/GEJC are eligible if the time to first recurrence or disease progression is greater than 6 months from the end of the last treatment. Prior use of anti-tumor Traditional Chinese Medicine preparations is allowed but must be discontinued at least 2 weeks before enrollment.
• ECOG performance status score of 0 or 1.
• Must have at least one measurable lesion according to RECIST v1.1 definitions.
• All acute toxicities caused by prior anti-tumor therapy or surgery must have resolved to Grade 0-1 (according to NCI CTCAE v5.0) or to the level specified in the inclusion/exclusion criteria. Alopecia, fatigue, and hearing loss, or other toxicities considered by the investigator not to pose a safety risk to the subject, are excluded.
• Adequate organ function (laboratory tests within 7 days prior to treatment):
‣ Hematology (No blood transfusion, G-CSF use, or drug correction within 14 days prior to screening):
⁃ White blood cell count (WBC) ≥ 3,000/mm³ (3.0 × 10⁹/L);
⁃ Absolute neutrophil count (ANC) ≥ 1,500/mm³ (1.5 × 10⁹/L);
⁃ Platelet count (PLT) ≥ 100,000/mm³ (100 × 10⁹/L);
⁃ Hemoglobin (Hb) ≥ 9.0 g/dL (90 g/L).
• Biochemistry (No albumin transfusion within 14 days prior to screening):
‣ Albumin ≥ 3.0 g/dL (30 g/L);
⁃ Creatinine ≤ 1.5 × Upper Limit of Normal (ULN) or Creatinine Clearance ≥ 50 ml/min (calculated using the Cockcroft-Gault formula);
⁃ Total Bilirubin (BIL) ≤ 1.5 × ULN;
⁃ Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels ≤ 2.5 × ULN; for patients with liver metastases, ≤ 5 × ULN.
• Coagulation: International Normalized Ratio (INR) ≤ 1.5, Prothrombin Time (PT), and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
• Urine: Urine protein \< 2+; if urine protein is ≥ 2+, 24-hour urine protein quantification must be ≤ 1g.
• Life expectancy ≥ 3 months.
• Women of childbearing potential must undergo a serum or urine pregnancy test within 7 days before starting treatment, with a negative result, and must not be lactating. All enrolled patients must use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.