PIN in Combination With Sintilimab in Previously Treated pMMR/MSS CRC With Hepatic Metastases

Korábbi kezelés

• Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
• Active central nervous system disease involvement (but allow patients with prior brain metastases treated at least 4 weeks prior to enrollment that are clinically stable and do not require intervention), or prior history of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 drug-related Central Nervous System (CNS) toxicity.
• Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered.
• Received cytotoxic chemicals, monoclonal antibodies, immunotherapy or other intervene within 4 weeks or 5 half-lives before enrollment.
• Received radiotherapy within 3 months before enrollment.
• Previous or concurrent cancer within 3 years prior to treatment start except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
• Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation.
• Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.

Más betegség

• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
• Any serious underlying medical (eg, pulmonary, renal, hepatic,gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements.
• Patients with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy.
• Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS).
• History of allergy or intolerance to study drug components.

Egyéb

• Participants with DNA mismatch repair-deficient or microsatellite instability-high (dMMR /MSI-H) CRC.
• Advanced CRC without hepatic metastases.
• The presence of uncontrollable serous membrane fluid, such as massive pleural effusion or ascites.
• Being participating any other trials or withdraw within 4 weeks.
• Researchers believe that other reasons are not suitable for clinical trials.

• Age 18-75 (inclusive).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and Estimated life expectancy of more than 3 months.
• Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic CRC with hepatic metastases have failed at least two lines of prior treatment.
• Tumor tissues were identified as pMMR by immunohistochemistry (IHC) method or MSS by polymerase chain reaction (PCR).
• At least one measurable lesion at baseline according to investigators Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1).
• Patients with injectable lesions (those suitable for direct injection or injection with the assistance of medical imaging) in the liver metastatic lesions, defined as follows: at least one injectable lesion in the skin, mucous membrane, subcutaneous tissue, lymph node or visceral organ with a longest diameter ≥10 mm.
• Subjects are willing to accept tumor rebiopsy in the process of this study.
• Adequate organ function as defined by the following criteria:
  • Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L, Platelet count ≥50 x 10\^9/ L, hemoglobin (Hgb) ≥ 80g/L ;
  • Serum creatinine≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥60 mL/min;
  • Serum aspartate amino transferase (AST) and alanine aminotransferase (ALT), ≤5 x ULN ; Total serum bilirubin ≤3 x ULN);
  • Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings;
  • International Normalized Ratio (INR) ≤ 1.5 times the upper limit of normal (ULN), and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN;
  • Baseline oxygen saturation >91% on room air.
• Previous treatments must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to <= grade 1 toxicity (except for hematological toxicities and clinically non-significant toxicities such as alopecia).
• Pregnancy tests for women of childbearing age shall be negative; Both men and women agreed to use effective contraception during treatment and during the subsequent 1 year.
• Voluntarily participate in this clinical trial and sign an informed consent form.