Back to resultsOH2 Oncolytic Viral Therapy in Solid Tumors
Primary Purpose
Solid Tumor, Gastrointestinal Cancer
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
OH2 injection, with or without irinotecan or HX008
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumor focused on measuring Oncolytic Virus
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed unresectable or recurrent/metastatic solid tumors.
- The patient must have failed the standard treatment (due to either disease progression or intolerable toxicity) or the standard of care had not been established for the specific condition.
- Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
- Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1.
- Life expectancy >3 months.
- The patient must have at least one tumor site appropriate for intratumoral injection.
- Adequate organ function.
- Participants of reproductive potential must be willing to use adequate contraception for the course of the study until 3 months after the last dose of any of the drugs in the study.
- Participants with a history of HSV infection must have recovered at least 3 months before the study.
- Willing and able to provide written informed consent and comply with the requirements of the study.
Exclusion Criteria:
- Uncontrolled concurrent illness including, but not limited to, severe cardiac disease, cerebralvascular disease, uncontrolled diabetes, uncontrolled hypertension, ongoing or active systemic infection, active peptic ulcer disease.
- Central nervous system (CNS) metastases with clinical symptoms
- Active infection or an unexplained fever > 38.5°C.
- Known Human Immunodeficiency Virus (HIV) infection, active Hepatitis B or Hepatitis C infection.
- Pregnant or lactating female.
- Patients who are receiving any other investigational agents.
- Known immediate or delayed hypersensitivity reaction to HSV.
- Previous malignancy within 5 years prior to study entry.
- Patients with any active autoimmune disease or history of autoimmune disease.
- Concurrent medical condition requiring the use of cortisol (>10mg/day prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment, except for inhalation or topical corticosteroids no more than 10 mg/day prednisone or equivalent.
- Familial, sociological or geographical conditions that, in the judgment of the investigator, do not permit compliance with the protocol.
Sites / Locations
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose escalation and dose expansion
Arm Description
A 3+3 dose-escalation strategy is used in the phase 1 part and 3 dose levels (10e6, 10e7 and 10e8 CCID50/mL) of OH2 are assessed as single agent and in combination with HX008. The recommended dose levels are then determined and adopted in the phase 2 part for dose-expansion. In the phase 2 dose-expansion part, OH2 will be delivered as single agent in cohort 1, in combination with irinotecan in cohort 2, in combination with HX008 in cohort 3 and 4. There are no comparator arms for these cohorts.
Outcomes
Primary Outcome Measures
The dose-limiting toxicities (DLTs) of OH2 injection as single agent and in combination with HX008 in patients with solid tumors
Primary outcome of phase 1.
The maximum-tolerated doses (MTDs) of OH2 injection as single agent and in combination with HX008 in patients with solid tumors
Primary outcome of phase 1.
The biodistribution and biologic effect of OH2 injection
Primary outcome of phase 1. The biodistribution of OH2 is evaluated by detection of viral loads in the blood, urine, and saliva. Additionally, the injection sites are swabbed for virus shedding. For the analyses of biologic effects, serum samples are collected for HSV serology assays and assessment of GM-CSF protein and GM-CSF RNA.
The anti-tumor activity of OH2 monotherapy and in combination with irinotecan or HX008
Primary outcome of phase 2.
Secondary Outcome Measures
The anti-tumor activity of OH2 monotherapy and in combination with HX008
Secondary outcome of phase 1.
The immunogenicity of OH2
Secondary outcome of phase 1. The immunogenicity of OH2 is evaluated by detection of anti-GM-CSF antibodies in the blood.
Full Information
NCT ID
NCT03866525
First Posted
February 28, 2019
Last Updated
November 7, 2022
Sponsor
Binhui Biopharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03866525
Brief Title
OH2 Oncolytic Viral Therapy in Solid Tumors
Official Title
Phase I/II Study of OH2 Injection, an Oncolytic Type 2 Herpes Simplex Virus Expressing Granulocyte Macrophage Colony-Stimulating Factor, in Malignant Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 2, 2019 (Actual)
Primary Completion Date
April 30, 2023 (Anticipated)
Study Completion Date
April 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Binhui Biopharmaceutical Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase I/II study evaluates the safety and efficacy of OH2 as single agent or in combination with HX008, an anti-PD-1 antibody, in patients with malignant solid tumors (gastrointestinal cancers, head and neck cancers, soft tissue sarcomas).
OH2 is an oncolytic virus developed upon genetic modifications of the herpes simplex virus type 2 strain HG52, allowing the virus to selectively replicate in tumors. Meanwhile, the delivery of the gene encoding human granulocyte macrophage colony-stimulating factor (GM-CSF) may induce a more potent antitumor immune response.
Detailed Description
This is a phase I/II study evaluating the safety and efficacy of OH2 injection in patients with malignant solid tumors.
In the phase I dose escalation part, three doses (1x10e6, 1x10e7, 1x10e8 CCID50/mL) of OH2 will be delivered intratumorally as single agent and in combination with HX008 to observe the DLTs and to identify the MTD. After the completion of phase I, the recommended dose for single agent and combination therapy will be determined for dose expansion in phase II.
The phase II part comprises of 4 cohorts. In cohort 1, patients will be treated at the recommended dose as defined in phase 1. In cohort 2, OH2 will be delivered in combination with irinotecan for the treatment of advanced gastrointestinal cancers. In cohort 3, OH2 will be injected in combination with HX008, and the first doses of the two anti-tumor agents will be administered on the same day. The treatments in cohort 4 will be identical as in cohort 3, except that the first dose of HX008 will be administered at the time of the third dose of OH2.
The biodistribution of OH2 is evaluated in the phase 1 part of the trial by detection of viral loads in the blood, urine, and saliva at different timepoints. In addition, the injection sites are swabbed for virus shedding on the next day of each dose from cycle 1-3.
Adverse events (AEs) and DLTs are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0). Radiographic imaging studies are performed using computed tomography or magnetic resonance imaging. Measurement of cutaneous or subcutaneous lesions are conducted with calipers. Evaluation of response are performed by the investigators using both the RECIST version 1.1 and the iRECIST criteria.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Gastrointestinal Cancer
Keywords
Oncolytic Virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose escalation and dose expansion
Arm Type
Experimental
Arm Description
A 3+3 dose-escalation strategy is used in the phase 1 part and 3 dose levels (10e6, 10e7 and 10e8 CCID50/mL) of OH2 are assessed as single agent and in combination with HX008. The recommended dose levels are then determined and adopted in the phase 2 part for dose-expansion.
In the phase 2 dose-expansion part, OH2 will be delivered as single agent in cohort 1, in combination with irinotecan in cohort 2, in combination with HX008 in cohort 3 and 4. There are no comparator arms for these cohorts.
Intervention Type
Biological
Intervention Name(s)
OH2 injection, with or without irinotecan or HX008
Intervention Description
OH2: Oncolytic Type 2 Herpes Simplex Virus Irinotecan: cytotoxic agent HX008: anti-PD-1 antibody
Primary Outcome Measure Information:
Title
The dose-limiting toxicities (DLTs) of OH2 injection as single agent and in combination with HX008 in patients with solid tumors
Description
Primary outcome of phase 1.
Time Frame
6 months
Title
The maximum-tolerated doses (MTDs) of OH2 injection as single agent and in combination with HX008 in patients with solid tumors
Description
Primary outcome of phase 1.
Time Frame
6 months
Title
The biodistribution and biologic effect of OH2 injection
Description
Primary outcome of phase 1. The biodistribution of OH2 is evaluated by detection of viral loads in the blood, urine, and saliva. Additionally, the injection sites are swabbed for virus shedding. For the analyses of biologic effects, serum samples are collected for HSV serology assays and assessment of GM-CSF protein and GM-CSF RNA.
Time Frame
6 months
Title
The anti-tumor activity of OH2 monotherapy and in combination with irinotecan or HX008
Description
Primary outcome of phase 2.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
The anti-tumor activity of OH2 monotherapy and in combination with HX008
Description
Secondary outcome of phase 1.
Time Frame
2 years
Title
The immunogenicity of OH2
Description
Secondary outcome of phase 1. The immunogenicity of OH2 is evaluated by detection of anti-GM-CSF antibodies in the blood.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed unresectable or recurrent/metastatic solid tumors.
The patient must have failed the standard treatment (due to either disease progression or intolerable toxicity) or the standard of care had not been established for the specific condition.
Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1.
Life expectancy >3 months.
The patient must have at least one tumor site appropriate for intratumoral injection.
Adequate organ function.
Participants of reproductive potential must be willing to use adequate contraception for the course of the study until 3 months after the last dose of any of the drugs in the study.
Participants with a history of HSV infection must have recovered at least 3 months before the study.
Willing and able to provide written informed consent and comply with the requirements of the study.
Exclusion Criteria:
Uncontrolled concurrent illness including, but not limited to, severe cardiac disease, cerebralvascular disease, uncontrolled diabetes, uncontrolled hypertension, ongoing or active systemic infection, active peptic ulcer disease.
Central nervous system (CNS) metastases with clinical symptoms
Active infection or an unexplained fever > 38.5°C.
Known Human Immunodeficiency Virus (HIV) infection, active Hepatitis B or Hepatitis C infection.
Pregnant or lactating female.
Patients who are receiving any other investigational agents.
Known immediate or delayed hypersensitivity reaction to HSV.
Previous malignancy within 5 years prior to study entry.
Patients with any active autoimmune disease or history of autoimmune disease.
Concurrent medical condition requiring the use of cortisol (>10mg/day prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment, except for inhalation or topical corticosteroids no more than 10 mg/day prednisone or equivalent.
Familial, sociological or geographical conditions that, in the judgment of the investigator, do not permit compliance with the protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jing Huang, MD
Phone
8610-87788102
Email
huangjingwg@163.com
Facility Information:
Facility Name
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bo Zhang, MD
Phone
8610-87788102
Email
zh.bo@outlook.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request are accessible from Binhui Biotech. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications.
IPD Sharing Time Frame
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in China or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
IPD Sharing Access Criteria
Qualified researchers may submit a request containing the research objectives, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement.
Citations:
PubMed Identifier
34757194
Citation
Wang Y, Jin J, Li Y, Zhou Q, Yao R, Wu Z, Hu H, Fang Z, Dong S, Cai Q, Hu S, Liu B. NK cell tumor therapy modulated by UV-inactivated oncolytic herpes simplex virus type 2 and checkpoint inhibitors. Transl Res. 2022 Feb;240:64-86. doi: 10.1016/j.trsl.2021.10.006. Epub 2021 Oct 29.
Results Reference
derived
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OH2 Oncolytic Viral Therapy in Solid Tumors
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