Iparomlimab and Tuvonralimab Combined With Apatinib and Irinotecan Hydrochloride for the Treatment of Advanced Alpha-fetoprotein-producing Gastric Cancer (AFPGC)

Prior treatment

• Patients with active brain metastases. Patients with asymptomatic brain metastases who have not received prior treatment and whose total number of brain metastases is ≤3 and the longest diameter is \< 1cm can be enrolled. Patients who have previously received treatment for brain metastases can be enrolled if they are clinically stable, have no evidence of new or expanded brain metastases, and have not used steroids for ≥14 days before the study intervention.
• Previously received immune checkpoint inhibitors other than anti-PD-1 /PD-L1 antibodies or other drugs/antibodies acting on T-cell co-stimulation or checkpoint pathways;
• Significant clinically significant bleeding symptoms or a clear bleeding tendency occurred within 3 months before enrollment; Gastrointestinal perforation and/or gastrointestinal fistula occurred within 6 months before enrollment; Arterial/venous thrombotic events that occurred within 6 months before enrollment, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.
• Significant malnutrition (weight loss of 5% within one month of signing the informed consent form or 15% within three months, or a reduction of half or more in food intake within one week), except for more than four weeks after the correction of malnutrition before the administration of the first dose of the study drug;
• History of other primary malignant tumors, excluding:
  • \<1\>Malignant tumors that achieved complete remission for at least 2 years before enrollment and did not require additional treatment during the study period; \<2\>Non-melanoma skin cancer or malignant freckle-like nevus that has been fully treated and has no evidence of disease recurrence; \<3\>Carcinoma in situ that has received adequate treatment and has no evidence of disease recurrence.
• According to the researcher's judgment, those with concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study;

Other illness

• Gastric cancer known to be squamous cell carcinoma, undifferentiated carcinoma or other tissue types, or adenocarcinoma mixed with other tissue types of gastric cancer;
• The patient currently has any diseases or conditions that affect the absorption of the drug;
• Combined with severe cardiovascular diseases, such as uncontrollable heart failure, coronary heart disease, arrhythmia, uncontrollable hypertension, etc.
• Known to be allergic to the drug used in this test;
• Known history of primary immunodeficiency or active pulmonary tuberculosis;
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
• There is a known history of human immunodeficiency virus (HIV) infection (i.e., HIV antibody positive);

Lab values

• Clinically uncontrolled active infections, such as acute pneumonia, active hepatitis B or hepatitis C (previous history of hepatitis B virus infection regardless of drug control, hepatitis B virus DNA≥1×104 copies /mL or 2000 IU/ml);

Other

• Inability to comply with the research plan or procedures;
• It is known to be in a HER2-positive state;
• Female patients who are pregnant or breastfeeding;
• The researchers considered patients unsuitable for inclusion in this study.

• 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.