NCT07127822RecruitingPhase 2
A Randomized, Controlled, Multi-centers, Non Inferiority Phase II Clinical Study Comparing Iparomlimab and Tuvonralimab With Standard Chemotherapy Combined With PD-1/PD-L1 Monoclonal Antibody as First-line Treatment for MSI-H/dMMR Recurrent/Metastatic Gastric Cancer
Peking University10 sites in 1 country106 target enrollmentStarted: December 15, 2025Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 106
- Locations
- 10
- Primary Endpoint
- Antitumor efficacy-Objective response rate (ORR)
Study Overview
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,
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1. Voluntarily willing to participate in the study and sign the written informed consent form
- •Age ≥18 years male or female .
- •Expected survival time ≥ 3 months
- •Patients with unresectable locally advanced, recurrent, or metastatic gastric/gastroesophageal junction adenocarcinoma diagnosed by histological or cytological examination:
- •Confirmed by PCR or next-generation sequencing(NGS) as microsatellite instability-high(MSI-H) . Patients with mismatch repair defecient identified by immunohistochemistry need to undergo PCR/NGS verification as MSI-H before treatment
- •Patients should not receive systematic anti-tumor treatment before, and for those who have received induction chemotherapy, concurrent radiochemotherapy, or neoadjuvant/adjuvant chemotherapy for curative purposes, the recurrence time must be at least 6 months from the end of the last treatment;
- •Agree to provide archived tumor tissue specimens or fresh tissue samples of primary or metastatic lesions within 3 years; If the patinet is unable to provide tumor tissue samples, they can be enrolled after evaluation by the researcher, provided that they meet other inclusion and
Exclusion Criteria
- •Patients must have at least one measurable lesion defined by RECIST 1.
- •European Cooperative Oncology Group (ECOG) ≤1
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥ 50%;
- •Patients must meet the following criteria at screening and before preconditioning (baseline). If any laboratory test result is abnormal referring to the following criteria,
- •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;
- •Urinary protein ≤ 2+or < 1000mg/24h;
- •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 .
- •Exclusion Criteria:
- •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:
- •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);
- •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;
- •Patients with a history of allergies to recombinant humanized antibodies who are allergic to any excipient components of the drug;
- •History of autologous or allogeneic stem cell transplantation;
- •Patients with a history of serious neurological or psychiatric disorders, including but not limited to: dementia, depression, epileptic seizures, bipolar disorder, etc;
- •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;
- •Patients who plan to receive live vaccines within 28 days prior to randomization;
- •Researchers evaluate situations where participation in this clinical trial is inappropriate due to complications or other reasons.
Arms & Interventions
Experimental arm
Experimental
iparomlimab and tuvonralimab
Intervention: Iparomlimab and Tuvonralimab (Drug)
Control arm
Active Comparator
standard first-line chemotherapy（FOLFOX/XELOX/SOX） combined with PD-1/PD-L1 antibody
Intervention: First line chemotherapy plus PD-1/PD-L1 antibody (Drug)
Outcomes
Primary Outcomes
Antitumor efficacy-Objective response rate (ORR)
Time Frame: 2 years
The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%).
Secondary Outcomes
- Antitumor efficacy-Overall survival (OS)(2 yeas)
- Antitumor efficacy-Progression-free survival (PFS)(2 years)
- Treatment related AEs(2 years)
- Antitumor efficacy-Duration of response (DOR)(2 years)
- Antitumor efficacy-Time to response (TTR)(2 years)
Investigators
Study Sites (10)
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