RC48 Plus Tislelizumab, Low-dose Capecitabine and Celecoxib for HER2-positive Metastatic Colorectal Cancer

Trial Title: RC48 Plus Tislelizumab, Low-dose Capecitabine and Celecoxib for HER2-positive Metastatic Colorectal Cancer

NCT ID: NCT05578287

Condition: Colorectal Cancer

Conditions: Official terms:
Colorectal Neoplasms
Celecoxib
Tislelizumab
Disitamab vedotin

Conditions: Keywords:
Salvage therapy
HER-2 positive
HER-2 ADC
PD-1 inhibitor

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Anti-HER2 ADC
Description: Disitamab Vedotin (2mg/kg, q2w), Tislelizumab (2mg/kg, q2w) combined with low-dose capecitabine 0.5g bid chemotherapy and the COX2 inhibitor celecoxib 200mg bid
Arm group label: Anti-HER2

Other name: Disitamab Vedotin

Other name: Tislelizumab

Other name: Capecitabin

Other name: Celecoxib

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.

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: The Sixth Affiliated Hospital of Sun Yat-sen University

Address:
City: Guangzhou
Zip: 510655
Country: China

Status: Recruiting

Contact:
Last name: Yanghong Deng, PhD

Phone: 008613925106525
Email: dengyanh@mail.sysu.edu.cn

Contact backup:
Last name: Jianwei Zhang, MD

Phone: 13480216906
Email: zhangjw25@mail.sysu.edu.cn

Investigator:
Last name: Yanhong Deng, PhD
Email: Principal Investigator

Start date: July 18, 2023

Completion date: December 25, 2025

Lead sponsor:
Agency: Sun Yat-sen University
Agency class: Other

Source: Sun Yat-sen University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05578287