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

NCT05578287 | Unknown Phase 2

• 1 other identifier: GIHSYSU-26
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer

Keywords

Salvage therapy; HER-2 positive; HER-2 ADC; PD-1 inhibitor

Outcome Measures

Primary Outcomes (2)

• Safety

  Safety was assessed by evaluation of AEs and serious AEs according to CTCAE 5.0

  1 year

• Feasibility

  Feasibility was determined based on any treatment -related AEs leading to delays over 15 days or discontinous of treatment.

  1 year

Secondary Outcomes (4)

• Objective response rate

  1 year

• disease control rate,DCR

  1 year

• Progression-free survival (PFS)

  1 year

• Overall Survival (OS)

  2 year

Study Arms (1)

Anti-HER2

EXPERIMENTAL

Disitamab Vedotin (2mg/kg, once every 2 weeks), Tislelizumab (2mg/kg, once every 2 weeks) combined with low-dose capecitabine 0.5g bid chemotherapy and the COX2 inhibitor celecoxib 200mg bid as salvage therapy

Drug: Anti-HER2 ADC

Interventions

Anti-HER2 ADC DRUG

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

Also known as: Disitamab Vedotin, Tislelizumab, Capecitabin, Celecoxib

Anti-HER2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Aged 18-75;
• 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;
• ECOG performance status score is 0-1;
• 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.
• 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;
• 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;
• Previous or no previous anti-HER2-targeted therapy, disease progression or intolerable toxicity during or within 3 months after treatment;
• Measurable lesions, according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1;

You may not qualify if:

• Complicated with intestinal obstruction, active bleeding or perforation and requiring emergency surgery;
• 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);
• 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;
• Thrombotic or embolic events occurred within the previous 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, deep vein thrombosis;
• The New York Heart Association (NYHA) class II or higher congestive Heart failure;
• 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;
• 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);
• The presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes mellitus, hypertension, pulmonary fibrosis, and acute pneumonia);
• 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);
• Previous recipients of PD-1/PD-L1 inhibitors or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies;
• A history of known or suspected allergies to any of the relevant drugs used in the study;
• Pregnant or lactating women.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

disitamab vedotin; tislelizumab; Capecitabine; Celecoxib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles

Central Study Contacts

Yanhong Deng, Ph.D

CONTACT

862013925106525; dengyanh@mail.sysu.edu.cn

Jianwei Zhang, Ph.D

CONTACT

00862013480216906; zhangjw25@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Medical Oncology, Clinical Professor

Study Record Dates

• First Submitted: October 8, 2022
• First Posted: October 13, 2022
• Study Start: July 18, 2023
• Primary Completion: December 15, 2024
• Study Completion: December 25, 2025
• Last Updated: December 7, 2023

Record last verified: 2023-12

Locations

CN (1)