Explore the Efficacy and Safety of Pembrolizumab and Disitamab Vedotin in HER2 Expressing Metastatic Colorectal Cancer Failed at Least Two Lines of Systemic Treatment

Shanghai Zhongshan Hospital0 sites30 target enrollmentJuly 1, 2022

ConditionsColorectal Neoplasms

InterventionsPembrolizumab Disitamab vedotin

DrugsPembrolizumab Disitamab vedotin

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: Colorectal Neoplasms
Sponsor: Shanghai Zhongshan Hospital
Enrollment: 30
Primary Endpoint: Objective response rate (ORR)
Status: Not yet recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

July 1, 2022

End Date

July 1, 2025

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Zhongshan Hospital

Responsible Party

Principal Investigator

Tianshu Liu

Director of Oncology Department

Shanghai Zhongshan Hospital

Eligibility Criteria

Inclusion Criteria

•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
•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.
•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.

Exclusion Criteria

•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)

Arms & Interventions

1

Pembrolizumab plus Disitamab vedotin

Intervention: Pembrolizumab

1

Pembrolizumab plus Disitamab vedotin

Intervention: Disitamab vedotin

Outcomes

Primary Outcomes

Objective response rate (ORR)

Time Frame: 24 months after the last subject participating in

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

Secondary Outcomes

Disease control rate (DCR)(24 months after the last subject participating in)
Overall survival (OS)(36 months after the last subject participating in)
Progression free survival time (PFS)(24 months after the last subject participating in)