Gastric / Gastroesophageal Junction Adenocarcinoma, MSI-H Cancer
Conditions
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,
Interventions
Iparomlimab and tuvonralimab for experimental arm
DRUGFirst 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
Sponsors
Peking University Cancer Hospital & Institute
Qilu Pharmaceutical Group Co., Ltd
Peking University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Voluntarily willing to participate in the study and sign the written informed consent form 2. Age ≥18 years male or female . 3. Expected survival time ≥ 3 months 4. Patients with unresectable locally advanced, recurrent, or metastatic gastric/gastroesophageal junction adenocarcinoma diagnosed by histological or cytological examination: 5. 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 6. 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; 7. 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
; 8. Patients must have at least one measurable lesion defined by RECIST 1.1. 9. European Cooperative Oncology Group (ECOG) ≤1 10. No severe cardiac dysfunction, left ventricular ejection fraction ≥ 50%; 11. Patients must meet the following criteria at screening and before preconditioning (baseline). If any laboratory test result is abnormal referring to the following 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 .
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antitumor efficacy-Objective response rate (ORR) | 2 years | The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antitumor efficacy-Progression-free survival (PFS) | 2 years | The period from the day of randomization to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first. |
| Antitumor efficacy-Overall survival (OS) | 2 yeas | The period from the day of randomization to any cause of death |
| Treatment related AEs | 2 years | — |
| Antitumor efficacy-Duration of response (DOR) | 2 years | The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause |
| Antitumor efficacy-Time to response (TTR) | 2 years | Time from randomization to first recording of PR or CR |
Countries
China
Contacts
Primary ContactLin Shen
Outcome results
None listed