OH2 Oncolytic Viral Therapy in Solid Tumors
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|ClinicalTrials.gov Identifier: NCT03866525|
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : July 21, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor Gastrointestinal Cancer||Biological: OH2 injection, with or without irinotecan or HX008||Phase 1 Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||300 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||April 2, 2019|
|Estimated Primary Completion Date :||April 30, 2022|
|Estimated Study Completion Date :||April 30, 2022|
Experimental: Dose escalation and dose expansion
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.
Biological: OH2 injection, with or without irinotecan or HX008
OH2: Oncolytic Type 2 Herpes Simplex Virus Irinotecan: cytotoxic agent HX008: anti-PD-1 antibody
- 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.
- The anti-tumor activity of OH2 monotherapy and in combination with HX008 [ Time Frame: 2 years ]Secondary outcome of phase 1.
- The immunogenicity of OH2 [ Time Frame: 2 years ]Secondary outcome of phase 1. The immunogenicity of OH2 is evaluated by detection of anti-GM-CSF antibodies in the blood.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03866525
|Contact: Jing Huang, MDfirstname.lastname@example.org|
|National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College||Recruiting|
|Beijing, Beijing, China, 100021|
|Contact: Bo Zhang, MD 8610-87788102 email@example.com|