A Single-arm Study to Evaluate the Safety and Efficacy of Recombinant Oncolytic Virus M1 (M1-c6v1) Combined With Anti-PD-1 Antibody SHR-1210 and Apatinib for Treatment of Patients With Advanced / Metastatic Hepatocellular Carcinoma

Liang Peng0 sites10 target enrollmentJanuary 25, 2021

ConditionsAdvanced/Metastatic Hepatocellular Carcinoma

InterventionsRecombinant oncolytic virus M1, anti PD-1 antibody, Apatinib

DrugsRecombinant oncolytic virus M1, anti PD-1 antibody, Apatinib

Overview

Phase: Phase 1
Intervention: Recombinant oncolytic virus M1, anti PD-1 antibody, Apatinib
Conditions: Advanced/Metastatic Hepatocellular Carcinoma
Sponsor: Liang Peng
Enrollment: 10
Primary Endpoint: Treatment related adverse events
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This is a single arm and open-label phase I trial to evaluate the safety, tolerability and efficacy of the oncolytic virus M1 （M1-c6v1）(iv 1×109 CCIC50, 1 dose per day, on day 1-5 each 28 day cycle) combined with anti-PD-1 antibody SHR-1201 (iv, 200 mg, once every two weeks) and Apatinib (po. 250 mg qd ) in the patients with advanced/metastatic hepatocellular carcinoma. 10 participants will be sequentially enrolled. The treatment duration is 12 months. All patients continue combination treatment until disease progression, unacceptable toxicity, death, or discontinuation for any reason.

Registry

clinicaltrials.gov

Start Date

January 25, 2021

End Date

October 30, 2022

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Liang Peng

Responsible Party

Sponsor Investigator

Principal Investigator

Liang Peng

Principle Investigator

Third Affiliated Hospital, Sun Yat-Sen University

Eligibility Criteria

Inclusion Criteria

•Aged 18-65 years old, both genders.
•To be confirmed to meet the clinical diagnosis standard, histologically or cytologically confirmed with hepatocellular carcinoma
•Life expectancy of at least 3 months.
•Patients was not received any systemic therapies to HCC.
•For patients with advanced hepatocellular carcinoma, liver function status Child-Pugh Class A or B (score\<=7).
•HCC staging is evaluated according to Diagnostic and therapeutic criteria for liver cancer (2019 Edition, National health commission, P.R.A)
•a: with vascular invasion and no extrahepatic metastasis, no matter the tumor condition; Child-Pugh A/B；PS 0\~
•b: with extrahepatic metastasis, no matter the tumor condition and vascular invasion; Child-Pugh A/B；PS 0\~2, not eligible for surgical and/or locoregional therapies.
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to
•Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria (The long diameter of the lesion on spiral CT scan was more than or equal to 10 mm or the short diameter of enlarged lymph node was more than or equal to 15 mm).

Exclusion Criteria

•Patients must not have had prior treatment with SHR-1210 or any other PD-L1 or PD-1 antagonists or any other oncolytic virus, and must not have had be enrolled in the phase III Study of Apatinib After Systemic Therapy in Patients With Hepatocellular Carcinoma.
•Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
•Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed.
•Known history of hypersensitivity to any components of the SHR-1210 formulation, or M1-c6v1 (mannitol, human albumin, trehalose).
•Active central nervous system (CNS) metastases with clinical symptoms (including cerebral edema, steroid requirement, or progressive disease). Subjects with brain or meningeal metastases that were previously treated must be clinically stable (magnetic resonance imaging \[MRI\] at least 4 weeks apart do not show evidence of new or enlarging metastases) and have discontinued immunosuppressive doses of systemic steroids (\> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration.
•Patients with other malignant tumor (except cured skin basal cell carcinoma and cervical carcinoma).
•Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class \> 2), ventricular arrhythmia which need medical intervention, left ventricular ejection fraction(LVEF) \< 50%.
•Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents(within 3 months): systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg.
•Coagulation abnormalities (PT\>16s、APTT\>43s、TT\>21s、Fbg\<2g/L), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
•Prior systemic chemotherapy, radiotherapy, immunotherapy, hormone therapy, surgery or target therapy within 4 weeks (Or 5 half-life of the drug, calculate the longer ) before the study drug administration, or any unresolved AEs \> Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (with the exception of any stable chronic toxicities not expected to resolve).