Iparomlimab and Tuvonralimab Injection Combined With Apatinib and Irinotecan Hydrochloride for the Treatment of Advanced Alpha-fetoprotein-producing Gastric Cancer (AFPGC) That Progresses From First-line PD-1 Combined Chemotherapy, A Prospective, Single-arm, Phase II Clinical Study
This study is a single-arm study aimed at evaluating the efficacy and safety of Iparomlimab and Tuvonralimab Injection combined with apatinib and irinotecan hydrochloride in the treatment of advanced alpha-fetoprotein gastric cancer (AFPGC) that progresses from first-line PD-1 combined with chemotherapy. The study enrolled patients with advanced gastric cancer and gastroesophageal junction cancer whose serum alpha-fetoprotein was greater than 20.0 ng/mL at the initial diagnosis and progressed after first-line PD-1 combined chemotherapy in a single center of the Fourth Hospital of Hebei Medical University. All patients underwent gastroscopy and were pathologically confirmed as Her-2 negative gastric adenocarcinoma, and had received PD-1 inhibitor treatment as the first-line treatment. Staged examinations include enhanced CT of the abdominal and pelvic cavities, plain CT scan of the chest, and color Doppler ultrasound of superficial lymph nodes. The enrolled patients received apalolitovolrelimab 5.0mg/kg, Q3W, d1; Apatinib mesylate, 0.25g, once daily; Irinotecan hydrochloride, 200mg/m², Q3W, d1. Combination therapy until the patient's disease progresses, or intolerable toxic and side effects occur, or until death or withdrawal of informed consent, or up to two years. The primary endpoint of the study was to assess the objective response rate (ORR) of combination therapy. Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and the incidence of adverse events, etc
• Voluntarily join this study and sign the informed consent form;
• Age≥18 years, both male and female are acceptable.
• Unresectable，Locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction that has been diagnosed by histopathological or cytological examination, with serum alpha-fetoprotein \> 20.0 ng/mL at the time of diagnosis. There is at least one measurable lesion (according to the RECIST v1.1, the long diameter of the measurable lesion on spiral CT scan is ≥10 mm or the short diameter of the enlarged lymph node is ≥15 mm; lesions that have received local treatment in the past can be used as target lesions after comfirmed progression according to the RECIST v1.1).
• Failure of previous first-line PD-1 combined chemotherapy treatment (disease progression during or after treatment); Those who relapse within 6 months (less than 183 days) after the end of adjuvant/neoadjuvant chemotherapy (oxaliplatin combined with fluorouracil) can be included in the study, and PD-1 inhibitors need to be combined in the first-line treatment.
• ECOG 0-1;
• Expected survival time ≥12 weeks;
• The functions of vital organs within 7 days before enrollment meet the following requirements (no blood components or cell growth factors are allowed to be used within 14 days before enrollment) :
• \<1\> Absolute neutrophil count ≥1.5×109/L; \<2\> platelet count ≥80×109/L; \<3\>Hemoglobin ≥9g/dL; \<4\>Total bilirubin \< 1.5 times ULN; \<5\>ALT and AST \< 2.5 times ULN (\< 5 times ULN in patients with liver metastasis); \<6\> serum creatinine ≤1 times ULN; \<7\>The endogenous creatinine clearance rate ≥ 50ml/min.
• Women of childbearing age should take effective contraceptive measures.
• Good compliance and cooperation with follow-up visits.