Disitamab Vedotin Combined With Tislelizumab in Advanced HER2 Positive Colorectal Cancer

Trial Title: Disitamab Vedotin Combined With Tislelizumab in Advanced HER2 Positive Colorectal Cancer

NCT ID: NCT05493683

Condition: Colorectal Neoplasms

Conditions: Official terms:
Colorectal Neoplasms
Tislelizumab
Disitamab vedotin

Conditions: Keywords:
Colorectal Cancer
Antibody Drug Conjugate
Disitamab Vedotin
Tislelizumab

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: Disitamab vedotin
Description: 2.0mg/kg，q2w
Arm group label: Combination of Disitamab Vedotin and Tislelizumab

Other name: RC48

Intervention type: Drug
Intervention name: Tislelizumab
Description: 400mg，q6w
Arm group label: Combination of Disitamab Vedotin and Tislelizumab

Summary: Among patients with colonrectal cancer, 5% were HER-2 positive, but the immunohistochemical results were mostly HER-2 2 +, which did not meet the indications of HER-2 targeting drugs. Disitamab Vedotin , which was listed in China last year, achieved similar results in HER-2 2+ and 3+, according to a clinical trial for breast cancer, suggesting that patients with colonrectal cancer may benefit from it. Tislelizumab is a PD-1 monoclonal antibody, which has been approved for a variety of tumors. It was reported that anti-HER-2 treatment can improve the tumor immune microenvironment and improve the efficacy of immunotherapy. At the same time, our previous studies showed that anti-PD-1 combined with Disitamab Vedotin can significantly inhibit the growth of colon tumor in mice. Therefore, Disitamab Vedotin and Tislelizumab were used in this study. This prospective clinical trial may bring new hope for the treatment of HER-2 positive CRC patients.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Signed the consents voluntarily; 2. All genders, age 18 or above; 3. Histological or cytological documentation of local advanced or metastatic unresectable colorectal carcinoma; 4. Patients with HER-2 overexpression (HER-2 IHC 2+ or IHC 3+) detected by immunohistochemistry; Resampling is recommended for samples over 3 years. 5. Subjects must have failed at treatments including fluoropyrimidine, oxaliplatin and irinotecan; For adjuvant or neoadjuvant chemotherapy, if disease progression occurs during treatment or within 6 months after treatment, it will be recorded as a first-line treatment; 6. Patients who have used anti-PD-1 or anti-PD-L1 inhibitors can be selected after stopping the treatment for more than 6 months; Patients who have used other anti HER-2 drugs with different mechanisms can be selected. 7. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.is necessary 8. Life expectancy of at least 3 months. 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 10. Have sufficient heart, lung, liver and kidney functions, and the laboratory examination within 14 days before screening meets the following indicators: i. Hemoglobin Hb ≥ 90 g/L ii. Neutrophil count ANC ≥ 1.5*10^9 /L iii. Platelet count PLT ≥ 80*10^9 /L iv. Albumin ALB ≥ 35 g/L v. Alanine aminotransferase ALT and aspartate aminotransferase AST ≤ 2.5 times the upper limit of the normal range, and liver metastasis patients ≤ 5 times the upper limit of the normal range. vi. Total bilirubin ≤ 1.5 times, or 2 times the upper limit of normal. vii. Creatinine Scr ≤ upper limit of normal range. viii. Prothrombin: PT-INR ≤ 2.3 or PT < 6 seconds compared with normal control 11. Subjects must complete the treatment and follow-up on schedule. according to the research plan. 12. No brain metastasis, no spinal cord compression. 13. Subjects agree to use blood samples for study analysis. 14. Women of childbearing age must be negative in pregnancy test and willing to take effective contraceptive measures during the study period. Exclusion Criteria: 1. Subjects are severe malnutrition or need tube feeding. 2. Major surgery has been performed within 30 days before treatment. 3. Previous treatment with anti-PD-1 / PD-L1 inhibitor, anti-CTLA-4 inhibitor, ADC drugs targeting HER-2 such as RC48 and T-DM1 within 6 months. 4. Other malignant tumors within 2 years and without cure (Except for patients with other early-stage tumors, after radical treatment, whom the researchers assess the recurrence risk of in the short term is small); 5. Subjects have active autoimmune system diseases that need systemic hormone therapy or anti autoimmune drug therapy. 6. Subjects with immunodeficiency or receiving systemic steroid therapy (prednisone > 10 mg / day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days before the first dose of combination therapy in this study; 7. Subjects with active infection and still need systemic treatment 7 days before the first dose of therapy in this study. 8. Subjects with uncontrollable systemic diabetes. 9. Subjects with interstitial lung disease, non infectious pneumonia or pulmonary fibrosis; 10. Subjects who have received allogeneic organ or stem cell transplantation in the past. 11. Subjects allergic to the drugs or related components involved in this study. 12. Participating in other interventional clinical studies. 13. The previous anti-tumor related adverses do not return to grade 1 in CTCAE before the first combination therapy. 14. Subjects who have uncontrolled hypertension by drugs, that is, systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg. 15. Thrombotic or hemorrhagic tendency or history within 60 days before the first medication, regardless of the severity. 16. Any serious or unstable medical condition#mental illness or known active alcohol or drug abuse or dependence.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Changzhou NO.2 People's Hospital

Address:
City: Changzhou
Zip: 150000
Country: China

Status: Recruiting

Contact:
Last name: Hua Jiang

Facility:
Name: The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University

Address:
City: Huai'an
Zip: 150000
Country: China

Status: Recruiting

Contact:
Last name: Xiaomin Zhong

Facility:
Name: The First Affiliated Hospital with Nanjing Medical University

Address:
City: Nanjing
Zip: 210029
Country: China

Status: Recruiting

Contact:
Last name: Yanhong Gu, Ph.D

Phone: 13813908678
Email: guluer@163.com

Investigator:
Last name: Yanhong Gu, Ph.D
Email: Principal Investigator

Facility:
Name: the Third Affiliated Hospital of Soochow University

Address:
City: Suzhou
Zip: 150000
Country: China

Status: Recruiting

Contact:
Last name: Wenwei Hu

Facility:
Name: Xuzhou Central Hospital

Address:
City: Xuzhou
Zip: 150000
Country: China

Status: Recruiting

Contact:
Last name: Yuan Yuan

Facility:
Name: Fudan University Shanghai Cancer Center

Address:
City: Shanghai
Country: China

Status: Recruiting

Contact:
Last name: Zhiyu Chen

Start date: August 1, 2022

Completion date: July 2025

Lead sponsor:
Agency: The First Affiliated Hospital with Nanjing Medical University
Agency class: Other

Source: The First Affiliated Hospital with Nanjing Medical University

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

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05493683