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

NCT07127822 | Not Yet Recruiting Phase 2

• 1 other identifier: PUCH MSI-H GC 1st
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Gastric / Gastroesophageal Junction Adenocarcinoma; MSI-H Cancer

Outcome Measures

Primary Outcomes (1)

• Antitumor efficacy-Objective response rate (ORR)

  The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%).

  2 years

Secondary Outcomes (5)

• Antitumor efficacy-Progression-free survival (PFS)

  2 years

• Antitumor efficacy-Overall survival (OS)

  2 yeas

• Treatment related AEs

  2 years

• Antitumor efficacy-Duration of response (DOR)

  2 years

• Antitumor efficacy-Time to response (TTR)

  2 years

Study Arms (2)

Experimental arm

EXPERIMENTAL

iparomlimab and tuvonralimab

Drug: Iparomlimab and Tuvonralimab

Control arm

ACTIVE COMPARATOR

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

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

Interventions

Iparomlimab and Tuvonralimab DRUG

Iparomlimab and tuvonralimab for experimental arm

Experimental arm

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

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

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Hematology: neutrophils (NE) ≥1.5×109 per liter, , platelets (PLT) ≥100×109per liter and hemoglobin (Hb) ≥8.0 g/dL.
• 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）,
• 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 .
• Pregnant or lactating women.
• Previous use of PD-1/PD-L1 monoclonal antibodies, CTLA-4 monoclonal antibodies, or monoclonal and bispecific drugs containing the aforementioned targets;
• 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;
• 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;
• Patients with uncontrolled pleural effusion, pericardial effusion, or ascites that require repeated drainage;
• 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
• 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;
• Patients with any severe and/or uncontrolled illnesses, including:
• \) 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.

Sponsors & Collaborators

• Peking University: lead
• Peking University Cancer Hospital & Institute: collaborator
• Qilu Pharmaceutical Group Co., Ltd: collaborator

Study Sites (1)

Department of GI Oncology, Peking University Cancer Hospital

Beijing, China

Location

Central Study Contacts

Lin Shen

CONTACT

（86）10-88196561; linshenpku@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2025
• First Posted: August 17, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)