Metastatic colorectal cancer with MSI-H/dMMR or POLE/POLD1 mutations
Conditions
Interventions
MSI-H/dMMR metastatic colorectal cancer patient group:Iparomlimab and Tuvonralimab Injection
POLE/POLD1 mutated metastatic colorectal cancer patient group:Iparomlimab and Tuvonralimab Injection
Sponsors
Chongqing University Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years old at the time of enrollment; 2. ECOG 0-1 points; 3. Cohort I:dMMR metastatic colorectal cancer as determined by mismatch repair (MMR) protein immunohistochemistry (IHC). MSI-H metastatic colorectal cancer determined by multiplex fluorescence polymerase chain reaction (PCR) capillary electrophoresis or next-generation sequencing (NGS). Cohort II:Metastatic colorectal cancer with DNA polymerase e (POLE) and DNA polymerase d1 (POLD1) mutations identified by NGS; 4. At least one measurable lesion as assessed by imaging according to the Efficacy Evaluation Criteria for Solid Tumors (RECIST v1.1); 5. The life expectancy was >=3 months; 6. The function of vital organs meets all of the following requirements (no transfusion of any blood components, no use of any cell growth factor and/or platelet-raising drugs within 2 weeks prior to initiation of study treatment): a) Hematology: i. Absolute neutrophil value (ANC) >= 1.5 ×10^9/L, ii. Hemoglobin (HB) >= 90 g/L. iii. Platelet count (PLT) >= 100× 10^9/L. b)Liver function: i. AST, ALT and ALP = 30g/L. c) Renal function: creatinine clearance (CrCl) calculated value >= 60 mL/min (CrCl calculated according to the Cockcroft-Gault formula) or serum creatinine <=1.5×ULN. d) Coagulation function: International normalized ratio (INR), activated partial thromboplastin time (APTT) and prothrombin time (PT) <= 1.5 × ULN; 7. Female subjects of childbearing age (theoretically 15~49 years old, including unmarried, married or widowed) female subjects must have a negative serum pregnancy test within 3 days before the first dose.Female subjects of childbearing potential must be using an acceptable method of contraception since screening and must agree to continue using a method of contraception for at least 6 months after the last dose of study drug.Non-neutered male subjects must be using an acceptable method of contraception from the start of screening until at least 6 months after the last dose.The specific time of discontinuation of contraception should be determined by the investigator; 8. Subjects voluntarily join this study, and are able to cooperate with treatment, regular assessment, follow-up and other requirements related to this study, and sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1. Presence of other components in tissue or cellular pathology except colorectal cancer; 2. Metastatic colorectal cancer that has received prior systemic therapy. If the patient has received adjuvant chemotherapy, the interval between the last adjuvant chemotherapy and the enrollment study should be >= 6 months; 3. Patient's AE had not recovered to NCI-CTCAE 10 mg daily prednisone or equivalent) or other immunosuppressive drugs (such as cyclophosphamide, azathioprine, methotrexate, thalidomide, TNF-a inhibitors, etc.) within 2 weeks prior to the first dose. Topical corticosteroids, nasal sprays, and inhaled steroids are allowed. The use of systemic corticosteroids for the prevention of contrast allergy is permitted; 14. Previous or current interstitial pneumonitis/lung disease requiring systemic hormonal therapy; 15. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation; 16. History of drug abuse, alcoholism, or drug abuse; 17. Pregnant or lactating females; 18. Subject has other underlying diseases, infections, treatments, laboratory test abnormalities that are not well controlled, which may confound the results of the study, affect the subject's full participation in the study, or may not be in the best interest of the subject.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety;Progression-free survival;2-year PFS rate;Overall Survival; | — |
Countries
China
Contacts
Public ContactYongsheng Li
Chongqing University Cancer Hospital
Outcome results
None listed