Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma
Conditions
Interventions
Experimental group:Iparomlimab and Tuvonralimab in Combination with Nab-Paclitaxel and Apatinib
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: 1.Male or female, aged >= 18 years. 2.Histologically or cytologically confirmed unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. 3.The subject must have experienced disease progression after receiving prior first-line therapy comprising a PD-1/PD-L1 inhibitor in combination with chemotherapy. 4.pMMR status confirmed by immunohistochemistry (IHC) on tumor tissue, OR MSS/MSI-L status confirmed by polymerase chain reaction (PCR) or next-generation sequencing (NGS). 5.HER2-negative. 6.At least one measurable lesion as defined by RECIST 1.1. 7.ECOG Performance Status score of 0-2. 8.Life expectancy of greater than 3 months. 9.Adequate organ function, meeting the following laboratory criteria within 7 days prior to the first dose:1)10.Hemoglobin (Hb) >= 7.5 g/dL; Absolute Neutrophil Count (ANC) >= 1.5 × 10?/L; Platelets (PLT) >= 75 × 10?/L; White Blood Cell Count (WBC) >= 3.0 × 10?/L. 2)Creatinine Clearance (CLcr) >= 45 mL/min, calculated using the Cockcroft-Gault equation. 3)Total Bilirubin (TBIL) = 50%. 4) International Normalized Ratio (INR) <= 1.5 × ULN and Activated Partial Thromboplastin Time (APTT) <= 1.5 × ULN. 10.Recovery from any Adverse Events (AEs) related to prior anti-cancer therapy to Grade <= 1 (according to CTCAE v5.0) before the first dose, excluding alopecia (any grade), peripheral sensory neuropathy <= Grade 2, hypomagnesemia <= Grade 2, lymphopenia <= Grade 2, and other abnormalities which, in the assessment of the Investigator and/or Sponsor, do not pose an unacceptable risk to the subject and for which the benefit of treatment outweighs the risk. 11.Subjects agree to use highly effective contraception from the time of signing the informed consent form until 180 days after the last dose of study treatment. Women of childbearing potential cannot be pregnant or breastfeeding. 12.Subjects must voluntarily participate in the study, provide signed informed consent, be compliant with the study protocol, and cooperate with follow-up procedures.
Exclusion criteria
Exclusion criteria: 1.Prior treatment with anti-CTLA-4 antibodies, immune checkpoint agonist antibodies (e.g., anti-ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), or cellular immunotherapy. 2.Prior first-line treatment with small molecule TKIs, such as regorafenib. 3.Prior first-line treatment with paclitaxel. 4.Known history of hypersensitivity to macromolecular protein preparations. Contraindications or hypersensitivity to any component of Iparomlimab/Tuvonralimab, nab-paclitaxel, and Apatinib. 5.Therapeutic use of full-dose oral or injectable anticoagulants or thrombolytic agents within 10 days prior to the initiation of study treatment (prophylactic use of low-dose aspirin, low molecular weight heparin, and rivaroxaban is permitted). 6.Requirement for systemic corticosteroid therapy (>10 mg prednisone daily or equivalent) or other immunosuppressive medications (e.g., cyclophosphamide, azathioprine, methotrexate, thalidomide, TNF-a inhibitors, etc.) within 2 weeks prior to the first dose. Topical corticosteroids, intranasal sprays, and inhaled corticosteroids are permitted. Use of systemic corticosteroids for prophylaxis against contrast agent allergy is permitted. 7.Active or potentially recurrent autoimmune disease, with the following exceptions: vitiligo, alopecia, psoriasis, or eczema not requiring systemic therapy; hypothyroidism due to autoimmune thyroiditis requiring only stable dose hormone replacement therapy; Type I diabetes mellitus requiring only stable dose insulin replacement therapy. 8.History of gastrointestinal perforation and/or fistula, or history of intestinal obstruction within 6 months prior to the first dose (subjects with initial signs/symptoms of incomplete/complete obstruction who received treatment and whose symptoms resolved may be enrolled per investigator assessment); extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic long-term diarrhea. 9.Symptomatic, untreated, or unstable brain metastases or leptomeningeal disease. 10.History of interstitial lung disease and/or pneumonitis, or pulmonary hypertension. 11.Poorly controlled hypertension (systolic BP >150 mmHg and/or diastolic BP >100 mmHg) despite standard treatment, poorly controlled or symptomatic diabetes mellitus, and uncontrolled or symptomatic cardiac arrhythmia. 12.Thromboembolic events within 6 months prior to initiation of study treatment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), or pulmonary embolism. 13.Myocardial infarction within the past 12 months, severe/unstable angina, or symptomatic congestive heart failure (NYHA Class III or IV). 14.Drainage of ascites, pleural effusion, or pericardial effusion within 4 weeks prior to enrollment. 15.Severe, non-healed, or dehisced wounds, and active ulcers or untreated fractures. 16.Concurrent active malignancy, except for malignancies that have been disease-free for over 5 years or appropriately treated and considered cured carcinoma in situ. 17.Known active HIV, HBV, or HCV infection. 18.Major surgery (excluding needle biopsy) within 4 weeks prior to the first dose without full recovery. 19.Any other condition deemed by the investigator as inappropriate for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease Control Rate, DCR;Progression-Free Survival, PFS;Overall Survival, OS;Quality of Life;Adverse Event, AE; | — |
Countries
China
Contacts
Public ContactJingde Chen
Shanghai East Hospital
Outcome results
None listed