Gastrointestinal Cancer, Solid Tumor
Conditions
Keywords
Oncolytic Virus
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.
Interventions
BIOLOGICALOH2 injection, with or without irinotecan or HX008
OH2: Oncolytic Type 2 Herpes Simplex Virus Irinotecan: cytotoxic agent HX008: anti-PD-1 antibody
Sponsors
Binhui Biopharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed unresectable or recurrent/metastatic solid tumors. 2. 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. 3. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. 4. Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1. 5. Life expectancy \>3 months. 6. The patient must have at least one tumor site appropriate for intratumoral injection. 7. Adequate organ function. 8. 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. 9. Participants with a history of HSV infection must have recovered at least 3 months before the study. 10. Willing and able to provide written informed consent and comply with the requirements of the study.
Exclusion criteria
1. 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. 2. Central nervous system (CNS) metastases with clinical symptoms 3. Active infection or an unexplained fever \> 38.5°C. 4. Known Human Immunodeficiency Virus (HIV) infection, active Hepatitis B or Hepatitis C infection. 5. Pregnant or lactating female. 6. Patients who are receiving any other investigational agents. 7. Known immediate or delayed hypersensitivity reaction to HSV. 8. Previous malignancy within 5 years prior to study entry. 9. Patients with any active autoimmune disease or history of autoimmune disease. 10. 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. 11. Familial, sociological or geographical conditions that, in the judgment of the investigator, do not permit compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The dose-limiting toxicities (DLTs) of OH2 injection as single agent and in combination with HX008 in patients with solid tumors | 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 | 6 months | Primary outcome of phase 1. |
| The biodistribution and biologic effect of OH2 injection | 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 | 2 years | Primary outcome of phase 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The anti-tumor activity of OH2 monotherapy and in combination with HX008 | 2 years | Secondary outcome of phase 1. |
| The immunogenicity of OH2 | 2 years | Secondary outcome of phase 1. The immunogenicity of OH2 is evaluated by detection of anti-GM-CSF antibodies in the blood. |
Countries
China
Contacts
Primary ContactJing Huang, MD
Outcome results
None listed