OH2 Oncolytic Viral Therapy in Solid Tumors

NCT03866525 | Recruiting Phase 1

• 1 other identifier: OH2-I-ST-02
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumor; Gastrointestinal Cancer

Keywords

Oncolytic Virus

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  6 months

• The anti-tumor activity of OH2 monotherapy and in combination with irinotecan or HX008

  Primary outcome of phase 2.

  2 years

Secondary Outcomes (2)

• The anti-tumor activity of OH2 monotherapy and in combination with HX008

  2 years

• The immunogenicity of OH2

  2 years

Study Arms (1)

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.

Biological: OH2 injection, with or without irinotecan or HX008

Interventions

OH2 injection, with or without irinotecan or HX008 BIOLOGICAL

OH2: Oncolytic Type 2 Herpes Simplex Virus Irinotecan: cytotoxic agent HX008: anti-PD-1 antibody

Dose escalation and dose expansion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Binhui Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 34757194 DERIVED

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Central Study Contacts

Jing Huang, MD

CONTACT

8610-87788102; huangjingwg@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 7, 2019
• Study Start: April 2, 2019
• Primary Completion: August 30, 2025
• Study Completion: August 30, 2025
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• 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.

Locations

CN (1)