Solid TumorPhase 1/2NCT03866525
OH2 Oncolytic Viral Therapy in Solid Tumors
A Phase 1/2 study testing OH2 injection, with or without irinotecan or HX008 in people with Solid Tumor and Gastrointestinal Cancer, run by Binhui Biopharmaceutical Co., Ltd. at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Solid Tumor, Gastrointestinal Cancer
- What is being tested?
- OH2 injection, with or without irinotecan or HX008
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- 2 Apr 2019to 30 Aug 2025
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, 100021
Bo Zhang, MD, 8610-87788102, zh.bo@outlook.com
About this study
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
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.
Read the 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.
- Conditions
- Solid Tumor, Gastrointestinal Cancer
- Being tested
- OH2 injection, with or without irinotecan or HX008
- Keywords
- Oncolytic Virus
- Medical subject headings
- Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OH2 injection, with or without irinotecan or HX008Biological
OH2: Oncolytic Type 2 Herpes Simplex Virus Irinotecan: cytotoxic agent HX008: anti-PD-1 antibody
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation and dose expansion | Experimental | 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. Receives: Biological: OH2 injection, with or without irinotecan or HX008 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
The anti-tumor activity of OH2 monotherapy and in combination with irinotecan or HX008
Primary outcome of phase 2.
Measured: 2 years
Secondary outcomes (2)
The anti-tumor activity of OH2 monotherapy and in combination with HX008
Secondary outcome of phase 1.
Measured: 2 years
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start2 Apr 2019
- Primary completion30 Aug 2025 (estimated)
- Study completion30 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Binhui Biopharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03866525
- Sponsor's protocol ID
- OH2-I-ST-02
- Status last verified
- Dec 2024
- First submitted
- 28 Feb 2019
- Last updated
- 20 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 34757194
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03866525
- Acronym / sponsor ID
- OH2-I-ST-02
- Conditions
- Solid Tumor, Gastrointestinal Cancer
- Keywords
- Oncolytic Virus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Binhui Biopharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 2 Apr 2019 (actual)
- Primary completion
- 30 Aug 2025 (estimated)
- Study completion
- 30 Aug 2025 (estimated)
- First posted
- 7 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose escalation and dose expansion | Experimental | Biological: OH2 injection, with or without irinotecan or HX008A 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OH2 injection, with or without irinotecan or HX008OH2: Oncolytic Type 2 Herpes Simplex Virus Irinotecan: cytotoxic agent HX008: anti-PD-1 antibody | Biological | Dose escalation and dose expansion |
Primary outcome
The dose-limiting toxicities (DLTs) of OH2 injection as single agent and in combination with HX008 in patients with solid tumors
Time frame: 6 months
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
Time frame: 6 months
Primary outcome of phase 1.
The biodistribution and biologic effect of OH2 injection
Time frame: 6 months
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
Time frame: 2 years
Primary outcome of phase 2.
2 secondary outcomes
The anti-tumor activity of OH2 monotherapy and in combination with HX008
Time frame: 2 years
The immunogenicity of OH2
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
- Derived from this study: PubMed 34757194Wang 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing OH2 injection, with or without irinotecan or HX008 in people with Solid Tumor and Gastrointestinal Cancer, run by Binhui Biopharmaceutical Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jing Huang, MD (8610-87788102, huangjingwg@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The dose-limiting toxicities (DLTs) of OH2 injection as single agent and in combination with HX008 in patients with solid tumors (time frame: 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03866525, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.