rc48 plus tislelizumab, low-dose capecitabine and celecoxib for her2-positive metastatic colorectal cancer

Conditions: Colorectal Cancer

Summary: as an established therapeutic target, her2 is widely used in a variety of tumors, including breast cancer and gastric cancer, among which a variety of drugs, including trastuzumab, lapatinib and t-dm1, have been approved for the treatment of breast cancer and gastric cancer with her2 amplification or overexpression. in colorectal cancer, her2 as a target has also been focused in recent years.


Eligibility criteria:
inclusion criteria: 1. a voluntarily signed and dated informed consent must be obtained from the subject in accordance with regulations and institutional guidelines before performing any protocol-related procedures other than routine care; 2. aged 18-75; 3. patients with pathologically or cytologically confirmed adenocarcinoma of the colon or rectum with evidence of locally advanced lesions or metastases that could not be resected; 4. ecog performance status score is 0-1; 5. detection of her2-positive tumor tissue at any time before screening; her2 positive was defined as the presence of her2 3+ positive staining in more than 50% of tumor cells on ihc. or patients with a her2 score of 2+ should also be tested by fish: her2/cep17 ratio ≥2.0. 6. appropriate organ function based on the following laboratory test values obtained during the screening period: neutrophil count ≥1.5×109/l, platelet count ≥75×109/l, serum total bilirubin ≤ 1.5× upper normal limits, unl), aspartate aminotransferase ≤ 2.5×unl, alanine aminotransferase ≤ 2.5×unl, serum creatinine ≤ 1.5×unl; 7. previous chemotherapy including oxaliplatin, irinotecan, and fluorouracil failed, including the following: subjects using oxaliplatin as adjuvant therapy should have treatment progression within 6 months of completion of adjuvant therapy; patients who refused standard chemotherapy because of unacceptable toxicity to treatment will be admitted to the study; 8. previous or no previous anti-her2-targeted therapy, disease progression or intolerable toxicity during or within 3 months after treatment; 9. measurable lesions, according to the response evaluation criteria for solid tumors (recist) version 1.1; exclusion criteria: 1. complicated with intestinal obstruction, active bleeding or perforation and requiring emergency surgery; 2. major surgery or severe trauma, such as laparotomy, thoracotomy, laparoscopic organ resection, etc. within the previous 4 weeks (the surgical incision should be completely healed before enrollment); 3. had active coronary artery disease, severe/unstable angina pectoris or newly diagnosed angina pectoris or myocardial infarction in the 12 months prior to study enrollment; 4. thrombotic or embolic events occurred within the previous 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, deep vein thrombosis; 5. the new york heart association (nyha) class ii or higher congestive heart failure; 6. human immunodeficiency virus (hiv) infection or known acquired immunodeficiency syndrome (aids), untreated active hepatitis (hepatitis b, defined as hbv-dna ≥ 500 iu/ml; hepatitis c, defined as hcv-rna above the detection limit of the assay) or co-infection with hepatitis b and c; 7. the presence of any active, known or suspected autoimmune disease. to allow enrollment of subjects in stable condition who do not require systemic immunosuppressive therapy, such as type i diabetes, hypothyroidism that requires only hormone replacement therapy, and skin conditions that do not require systemic treatment (e.g., vitiligo, psoriasis, and alopecia); 8. the presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes mellitus, hypertension, pulmonary fibrosis, and acute pneumonia); 9. common terminology criteria for adverse events that have not resolved due to any previous treatment ctcae) (version 5.0) grade 2 or higher toxicity (except peripheral neurotoxicity, anemia, alopecia, skin pigmentation); 10. previous recipients of pd-1/pd-l1 inhibitors or anti-cytotoxic t-lymphocyte-associated protein 4 (ctla-4) antibodies; 11. a history of known or suspected allergies to any of the relevant drugs used in the study; 12. pregnant or lactating women.

Keywords: salvage therapy her-2 positive her-2 adc pd-1 inhibitor