Iparomlimab + Tuvonralimab with apatinib and irinotecan for AFP-producing advanced stomach or gastroesophageal junction cancer

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 will test whether combining two immune drugs (iparomlimab and tuvonralimab) with apatinib and irinotecan helps people with advanced AFP-producing stomach or gastroesophageal junction cancer after progression on first-line PD-1 plus chemotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hebei Medical University Fourth Hospital (other)
• Drugs / interventions: chemotherapy, Iparomlimab, Tuvonralimab, apalolitovolrelimab, apatinib
• Locations: 1 site (Shijiazhuang, Hebei)
• Trial ID: NCT07289997 on ClinicalTrials.gov

What this trial studies

This is a single-arm Phase 2 trial at Hebei Medical University Fourth Hospital testing a four-drug combination: QL1706 (iparomlimab and tuvonralimab), the VEGFR2 inhibitor apatinib, and the chemotherapy irinotecan, in patients with advanced alpha-fetoprotein-producing gastric or gastroesophageal junction adenocarcinoma. Eligible patients must be adults with HER2-negative disease, serum AFP > 20 ng/mL at diagnosis, measurable disease by RECIST v1.1, and progression after first-line PD-1 combined with chemotherapy. Participants receive the combined regimen and are monitored with imaging (CT of chest/abdomen/pelvis), clinical labs, and safety assessments to measure tumor response and adverse events. The main goals are to characterize response rates and safety in this aggressive AFPGC subgroup.

Who should consider this trial

Good fit: Adults (>=18) with unresectable locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma, serum AFP > 20 ng/mL at diagnosis, at least one measurable lesion per RECIST v1.1, and documented progression after first-line PD-1 plus chemotherapy are ideal candidates.

Not a fit: Patients who are HER2-positive, who have not progressed after PD-1 plus chemotherapy, who have very poor performance status, or who cannot attend the single study site are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If effective, this combination could increase tumor response and extend disease control and survival for patients with advanced AFP-producing gastric cancer who have few options after first-line therapy.

How similar studies have performed: Combining PD-1 and CTLA-4 blockade with anti-angiogenic agents and chemotherapy has shown activity in broader gastric cancer studies, but specific evidence for AFP-producing gastric cancer is limited, making this approach promising but relatively novel for AFPGC.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily join this study and sign the informed consent form;
2. Age≥18 years, both male and female are acceptable.
3. 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).
4. 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.
5. ECOG 0-1;
6. Expected survival time ≥12 weeks;
7. 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.
8. Women of childbearing age should take effective contraceptive measures.
9. Good compliance and cooperation with follow-up visits.

Exclusion Criteria:

1. Inability to comply with the research plan or procedures;
2. It is known to be in a HER2-positive state;
3. Gastric cancer known to be squamous cell carcinoma, undifferentiated carcinoma or other tissue types, or adenocarcinoma mixed with other tissue types of gastric cancer;
4. The patient currently has any diseases or conditions that affect the absorption of the drug;
5. Combined with severe cardiovascular diseases, such as uncontrollable heart failure, coronary heart disease, arrhythmia, uncontrollable hypertension, etc.
6. 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.
7. Known to be allergic to the drug used in this test;
8. 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;
9. 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.
10. 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);
11. Known history of primary immunodeficiency or active pulmonary tuberculosis;
12. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
13. There is a known history of human immunodeficiency virus (HIV) infection (i.e., HIV antibody positive);
14. 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;
15. 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.
16. Female patients who are pregnant or breastfeeding;
17. 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;
18. The researchers considered patients unsuitable for inclusion in this study.

Where this trial is running

Shijiazhuang, Hebei

• Hebei Medical University Fourth Hospital — Shijiazhuang, Hebei, China (RECRUITING)

Study contacts

• Study coordinator: Fengbin Zhang

Conditions: AFP Gastric or Gastroesophageal Junction Adenocarcinoma, PD-1/CTLA-4, AFPGC, Immunotherapy, immunotherapy