Disitamab Vedotin Combined With Tislelizumab in Advanced HER2 Positive Colorectal Cancer

October 19, 2022 updated by: The First Affiliated Hospital with Nanjing Medical University

A Single Arm, Open Label, Multiple Center, Prospective Study of Disitamab Vedotin Combined With Tislelizumab in HER2 Positive Advanced Colorectal Cancer Failed at Least Two Lines of Systemic Treatment.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Shiyun Cui, Dr

Study Locations

  • China
    • Jiangsu
      • Changzhou, Jiangsu, China, 150000
        • Recruiting
        • Changzhou No.2 People's Hospital
      • Huai'an, Jiangsu, China, 150000
        • Recruiting
        • The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University
        • Contact:
          • Xiaomin Zhong
      • Nanjing, Jiangsu, China, 210029
        • Recruiting
        • The First Affiliated Hospital with Nanjing Medical University
        • Contact:
        • Principal Investigator:
          • Yanhong Gu, Ph.D
      • Suzhou, Jiangsu, China, 150000
        • Recruiting
        • The Third Affiliated Hospital of Soochow University
        • Contact:
          • Wenwei Hu
      • Xuzhou, Jiangsu, China, 150000
        • Recruiting
        • Xuzhou Central Hospital
        • Contact:
          • Yuan Yuan
    • Shanghai
      • Shanghai, Shanghai, China
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:
          • Zhiyu Chen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combination of Disitamab Vedotin and Tislelizumab
Disitamab Vedotin 2.0mg/kg q2w+Tislelizumab 400mg q6w. The treatment of Disitamab Vedotin + Tislelizumab will continue until the tumor progression confirmed by imaging, or up to 2 years, or intolerable toxic reactions, or other conditions determined by the researchers.
Drug: Disitamab vedotin
2.0mg/kg，q2w
Other Names:
  • RC48
Drug: Tislelizumab
400mg，q6w

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate(ORR)
Time Frame: up to 2 years
The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)
up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival(PFS)
Time Frame: From date of subjects until the date of first documented progression or death from any cause, whichever came first, assessed up to 24 months
PFS was defined as the time from assignment to disease progression radiological/clinical or death due to any cause, whichever occurs first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.
From date of subjects until the date of first documented progression or death from any cause, whichever came first, assessed up to 24 months
Overall Survival (OS)
Time Frame: From assignment of the first subject until 32 death events observed, up to 2 years.
OS is defined as the time from date of assignment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
From assignment of the first subject until 32 death events observed, up to 2 years.
Disease control rate (DCR)
Time Frame: up to 2 years
DCR is defined as the percentage of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD).
up to 2 years
Safety and Feasibility
Time Frame: up to 2 years
Safety is defined as the incidence of Grade 3-4 Treatment-Related Adverse Events (TRAEs) from the day of neoadjuvant therapy to 30 days after surgery or within 90 days after last neoadjuvant treatment. Feasibility of surgery is defined as the incidence of TRAEs causing surgery delay of ≥30 days and/or inoperable patients.Feasibility of surgery is defined as the incidence of TRAEs causing surgery delay of ≥30 days and/or inoperable patients.
up to 2 years
Duration of Response (DOR)
Time Frame: up to 2 years
DOR is defined as the time from randomization to disease progression or death in patients who achieve complete or partial response.
up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Investigators

  • Principal Investigator: Gu Yanhong, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2022

Primary Completion (Anticipated)

July 1, 2025

Study Completion (Anticipated)

July 1, 2025

Study Registration Dates

First Submitted

August 7, 2022

First Submitted That Met QC Criteria

August 7, 2022

First Posted (Actual)

August 9, 2022

Study Record Updates

Last Update Posted (Actual)

October 21, 2022

Last Update Submitted That Met QC Criteria

October 19, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KEEP-G 07

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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