Pembrolizumab and Disitamab Vedotin in HER2-expressing Metastatic Colorectal Cancer

NCT05333809 | Unknown Phase 2

• 1 other identifier: HERPANDA
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, multi-center, phase Ⅱ study. This study will evaluate the efficacy and safety of pembrolizumab in combination with disitamab vedotin in subject with HER2-expressing metastatic Colorectal Cancer (mCRC).

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  proportion of patients with complete and partial remission in the best efficacy

  24 months after the last subject participating in

Secondary Outcomes (3)

• Disease control rate (DCR)

  24 months after the last subject participating in

• Progression free survival time (PFS)

  24 months after the last subject participating in

• Overall survival (OS)

  36 months after the last subject participating in

Study Arms (1)

1

EXPERIMENTAL

Pembrolizumab plus Disitamab vedotin

Drug: Pembrolizumab; Drug: Disitamab vedotin

Interventions

Pembrolizumab DRUG

an anti-PD-1 monoclonal antibody

1

Disitamab vedotin DRUG

HER2-ADC

1

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of histologically or cytologically confirmed unresectable metastatic CRC (KRAS, NRAS and BRAF wild type) with HER-2 expression (IHC2+ or IHC 3+) will be enrolled in this study.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Histologically and/or cytologically confirmed colorectal cancer, including:
• （a) Unresectable metastatic colorectal adenocarcinoma (b)Evaluable or measurable HER2 expressing (IHC 3+ or IHC 2+) disease
• Have received at least 2 prior treatments with systemic chemotherapy regimen until disease progression or intolerance; the patients with disease progression during or within 6 months after the adjuvant or neoadjuvant chemotherapy treatment should be recorded as first-line treatment; There is no restriction on whether the patient has received previous anti-HER2 treatment; for patients who have received previous anti-HER2 treatment, tissue re-biopsy should be done to confirm the expression of HER2 before enrollment; for patients who haven't received previous anti-HER2 treatment, HER2 status may refer to previous testing results from Tier 1 hospital.
• Have measurable disease based on RECIST 1.1.
• Have life expectancy of at least 3 months
• Have adequate organ function as defined in the following table (Table 4).
• Male participants: A male participant must agree to use a contraception as detailed in Appendix 2 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants: The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. A female participant is eligible to participate if she is not pregnant (see Appendix 2), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

You may not qualify if:

• Patients with any previous histological or hematological test showing mismatch repair gene deletion (dMMR), microsatellite instability (MSI-H)
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA-4 or any cellular immunotherapy; has received prior therapy with other HER2-ADC tubulin inhibitors (such as T-DM1, RC-48, DS8201, etc.) or participated in similar clinical studies;
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, pulmonary fibrosis, acute lung disease, or uncontrolled systemic diseases (i.e., diabetes, hypertension).
• Clinically uncontrollable diarrhea
• Has a chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection, etc. Patients with a history of active TB infection ≥1 year prior to screening should also be excluded, unless proof can be provided that appropriate treatment has been completed.
• Has known active CNS metastases and/or carcinomatous meningitis.
• Clinically significant pleural effusion, pericardial effusion or ascites requiring multiple drains within 2 weeks prior to treatment
• Known second primary malignancy or additional malignancy within the past 5 years (Participants with basal cell carcinoma of the skin or carcinoma in situ of the cervix that have undergone potentially curative therapy are not excluded)
• Uncontrolled diabetes or electrolyte disorder after the standard medical treatment
• Has a known history of Human Immunodeficiency Virus (HIV) infection.
• Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA \> 500 IU/mL and patients with positive HCV) RNA should be excluded.
• Note: Hepatitis B and C screening tests are not required unless:
• Known history of HBV and HCV infection

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

pembrolizumab; disitamab vedotin

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

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 Oncology Department

Study Record Dates

• First Submitted: April 12, 2022
• First Posted: April 19, 2022
• Study Start: July 1, 2022
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2025
• Last Updated: April 20, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share