Assessing Iparomlimab and Tuvonralimab in Recurrent or Metastatic MSI-H/dMMR Gastric Cancer

NCT ID: NCT07127822

Last Updated: 2025-08-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2028-12-31

Brief Summary

A randomized controlled phase II study exploring first-line treatment options for recurrent/metastatic MSI-H gastric cancer

Detailed Description

This is a randomized controlled, non-inferiority design phase II study in the first-line treatment of recurrent/metastatic MSI-H gastric cancer, using iparomlimab and tuvonralimab and standard first-line chemotherapy combined with PD-1/PD-L1 antibody in two cohorts, respectively,

Conditions

Gastric / Gastroesophageal Junction Adenocarcinoma; MSI-H Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental arm

iparomlimab and tuvonralimab

Group Type: EXPERIMENTAL

Iparomlimab and Tuvonralimab

Intervention Type: DRUG

Iparomlimab and tuvonralimab for experimental arm

Control arm

standard first-line chemotherapy（FOLFOX/XELOX/SOX） combined with PD-1/PD-L1 antibody

Group Type: ACTIVE_COMPARATOR

First line chemotherapy plus PD-1/PD-L1 antibody

Intervention Type: DRUG

standard first-line chemotherapy（FOLFOX/XELOX/SOX）combined with PD-1/PD-L1 antibody for control arm

Interventions

Iparomlimab and Tuvonralimab

Iparomlimab and tuvonralimab for experimental arm

Intervention Type: DRUG

First line chemotherapy plus PD-1/PD-L1 antibody

standard first-line chemotherapy（FOLFOX/XELOX/SOX）combined with PD-1/PD-L1 antibody for control arm

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

1. Hematology: neutrophils (NE) ≥1.5×109 per liter, , platelets (PLT) ≥100×109per liter and hemoglobin (Hb) ≥8.0 g/dL.

2. Blood chemistry: creatinine clearance ≥50 mL/min, Creatinine (Cr) ≤ 1.5 × ULN, alanine aminotransferase (ALT) ≤2.5×ULN（Gilbert syndrome or liver metastasis subjects ≤ 5 × ULN）, aspartate aminotransferase (AST) ≤2.5×ULN（Gilbert syndrome or liver metastasis subjects ≤ 5 × ULN）, total bilirubin (TB) ≤1.5×ULN（Gilbert syndrome or liver metastasis subjects ≤ 3 × ULN）,

3. International normalized ratio (INR) ≤ 1.5, and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 12. Urinary protein ≤ 2+or < 1000mg/24h; 13. Women of childbearing potential must have negative serum pregnancy test result at screening and before preconditioning and agree to use an effective and reliable contraceptive method for at least 1 year after the last study treatment. Te acceptable methods include bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusion; any approved oral, injection or implantation of hormone; or barrier contraceptive method: condoms containing spermicidal .

1. Pregnant or lactating women.

2. Previous use of PD-1/PD-L1 monoclonal antibodies, CTLA-4 monoclonal antibodies, or monoclonal and bispecific drugs containing the aforementioned targets;

3. Existence of any active autoimmune disease or history of autoimmune disease (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis; asthma in which subjects require bronchodilators for medical intervention cannot be included); However, the following diseases are allowed to be included: vitiligo, psoriasis, alopecia without systemic treatment, well controlled type I diabetes, hypothyroidism with normal thyroid function after replacement treatment;

4. Patients who require immunosuppressive therapy, systemic or absorbable local hormone therapy to achieve immunosuppressive goals (calculated as prednisone, dose>10mg/day or other therapeutic hormones) and continue to use it within 2 weeks of the first administration;

5. Patients with uncontrolled pleural effusion, pericardial effusion, or ascites that require repeated drainage;

6. Patients with uncontrollable symptoms of brain metastasis, spinal cord compression, malignant meningitis, or brain or pia mater diseases detected by CT or MRI examination during screening within 4 weeks before the first administration

7. Patients who have received non systematic anti-tumor therapy within 3 weeks prior to the start of treatment, including but not limited to surgery, radiation therapy, interventional therapy, and anti-tumor traditional Chinese medicine treatment (based on the indications in the Chinese medicine instructions, and may also be enrolled after a 2-week washout period). Patients whose adverse events caused by previous treatment (excluding hair loss) have not recovered to ≤ CTCAE grade 2 are not within the above range;

8. Patients with any severe and/or uncontrolled illnesses, including:

1) Patients with poor blood pressure control (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg) 2) Patients who experience unstable angina, myocardial infarction, ≥ grade 2 congestive heart failure, or arrhythmia requiring treatment within 6 months of initial administration (including QTc ≥ 480ms); 3) Active or uncontrolled severe infection (≥ CTCAE grade 2 infection); 4) A history of clinically significant liver disease, including viral hepatitis, known as a carrier of hepatitis B virus (HBV), must exclude active HBV infection, i.e. HBV DNA positive (>2000 IU/mL); Known hepatitis C virus infection (HCV) and HCV RNA positivity (>1 × 103 copies/mL), or other decompensated liver diseases or chronic hepatitis requiring antiviral therapy; 5) HIV test positive 6) Poor control of diabetes (fasting blood glucose ≥ CTCAE level 2); 9. Patients who have experienced severe infections (CTCAE>grade 2) within the first 4 weeks of randomization, such as severe pneumonia, bacteremia, sepsis, tuberculosis, etc; Indications of pulmonary infection or active pulmonary inflammation within the first 2 weeks of randomization; 10. Patients with a history of allergies to recombinant humanized antibodies who are allergic to any excipient components of the drug; 11. History of autologous or allogeneic stem cell transplantation; 12. Patients with a history of serious neurological or psychiatric disorders, including but not limited to: dementia, depression, epileptic seizures, bipolar disorder, etc; 13. Patients diagnosed as active malignant tumor within the first 3 years of randomization, except for the following cases: radical skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ and/or radical resection of carcinoma in situ, which the researchers think can be included; 14. Patients who plan to receive live vaccines within 28 days prior to randomization; 15. Researchers evaluate situations where participation in this clinical trial is inappropriate due to complications or other reasons.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role: collaborator

Qilu Pharmaceutical Group Co., Ltd

UNKNOWN

Sponsor Role: collaborator

Peking University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of GI Oncology, Peking University Cancer Hospital

Beijing, , China

Countries

China

Central Contacts

Lin Shen

Role: CONTACT

linshenpku@163.com

（86）10-88196561

Facility Contacts

Lin Shen

Role: primary

linshenpku@163.com

(86)10-88196561

Other Identifiers

PUCH MSI-H GC 1st

Identifier Type: -

Identifier Source: org_study_id