First-line Treatment of Gastric or Gastroesophageal Junction Adenocarcinoma With Dual Immunotherapy Combined With Chemotherapy

A Prospective, Single-arm, Multicenter, Phase II Clinical Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Modified FLOT Regimen (TFOX) as First-line Treatment for HER2-negative Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

A prospective, single-arm, multicenter, Phase II clinical study of Apatolimab Tovolimab (QL1706) in combination with modified FLOT regimen (TFOX) as first-line treatment for HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma

Inclusion Criteria:

• 1. The participant voluntarily agrees to participate in this study, signs the informed consent form, and strictly adheres to the requirements of the study protocol.
• 2. Age ≥18 years and ≤75 years at enrollment, regardless of gender.
• 3. Histologically confirmed unresectable locally advanced or metastatic G/GEJ adenocarcinoma, with inclusion criteria specifying HER2- status (HER2+ status defined as IHC3+ or IHC2+ and FISH+).
• 4. No prior systemic treatment for unresectable locally advanced or metastatic G/GEJ adenocarcinoma; previous neoadjuvant and/or adjuvant therapy is acceptable, but all systemic treatments must have been completed at least 12 months prior to the diagnosis of unresectable or metastatic disease.
• 5. At least one measurable tumor lesion according to RECIST 1.1 criteria.
• 6. ECOG PS of 0 or 1.
• 7. Life expectancy ≥3 months.
• 8. Fully recovered from any toxicities related to prior treatments prior to enrollment in the study.
• 9. BMI >18.
• 10. Adequate function of major organs
• 11. Fertile subjects must use appropriate contraception during the study and for 120 days after the end of the study. They must have a negative serum pregnancy test within 7 days prior to enrollment and must not be breastfeeding.

Exclusion Criteria:

• 1. Any unstable systemic disease: including active infection, uncontrolled hypertension, unstable angina, angina that started within the last 3 months, congestive heart failure (New York Heart Association [NYHA] ≥Class II), myocardial infarction within 6 months prior to enrollment, severe arrhythmias requiring medication, or hepatic, renal, or metabolic diseases.
• 2. Symptomatic brain and/or leptomeningeal metastases.
• 3. Known deficiency of dihydropyrimidine dehydrogenase (DPD).
• 4. QT/QTc interval >450 ms for males, >470 ms for females.
• 5. History of other malignancies within 5 years prior to enrollment, with the exception of adequately treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin.
• 6. History of organ transplantation or autologous/allogeneic stem cell transplantation.
• 7. Currently receiving systemic immunotherapy or hormone therapy other than physiologic replacement therapy.
• 8. Other concurrent anti-tumor treatments.
• 9. Known hypersensitivity or allergic reaction to any component of the study treatment.
• 10. Previous exposure to docetaxel or oxaliplatin (except for adjuvant chemotherapy).
• 11. Previous exposure to immune checkpoint inhibitors (e.g., anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies), immune checkpoint agonists (e.g., antibodies targeting ICOS, CD40, CD137, GITR, OX40), or any immunotherapy targeting tumor immune mechanisms.
• 12. Participants with severe bone marrow failure.
• 13. Any disease, metabolic disorder, or physical examination or laboratory findings that suggest contraindications to the study drug or high-risk factors for treatment complications.
• 14. Known or self-reported human immunodeficiency virus (HIV) infection.
• 15. Participants who are HBV or HCV positive.
• 16. Pregnant or breastfeeding.
• 17. Received a live vaccine within 4 weeks prior to the first dose, or plans to receive a live vaccine during the study.
• 18. Participated in any investigational drug treatment or used any investigational device within 4 weeks prior to the first dose.
• 19. Any condition that the investigator believes may pose a risk to the participant receiving the study drug, or may interfere with the evaluation of the study drug, the safety of the participant, or the interpretation of the study results.