OH2 Injection in Solid Tumors

• ClinicalTrials.gov Identifier: NCT04386967
• Recruitment Status: Recruiting
• First Posted: May 13, 2020
• Last Update Posted: April 4, 2022
• Sponsor: Binhui Biopharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Binhui Biopharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: April 13, 2020
• First Posted Date: May 13, 2020
• Last Update Posted Date: April 4, 2022
• Actual Study Start Date: November 22, 2018
• Estimated Primary Completion Date: March 13, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 11, 2020)

• Further evaluation of dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of OH2 in patients with solid tumors [ Time Frame: 12 months ]
• The dose-limiting toxicity (DLT) of OH2 injection and Keytruda in patients with solid tumors [ Time Frame: 12 months ]
• The maximum-tolerated dose (MTD) of OH2 injection in combination with Keytruda in patients with solid tumors [ Time Frame: 12 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 11, 2020)

• The response rate of patients with solid tumors receiving OH2 injection monotherapy and OH2 injection in combination with Keytruda [ Time Frame: 12 months ]
• The biodistribution of OH2 injection as determined by the concentration of OH2 in blood, urine and feces of participating patients [ Time Frame: 12 months ]
• The immunogenicity of OH2 injection as determined by the detection of antibodies in response to OH2 and GM-CSF [ Time Frame: 12 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: OH2 Injection in Solid Tumors
• Official Title: Open and Incremental Phase I Clinical Trial of Recombinant Human GM-CSF Type II Herpes Simplex Virus (OH2) Injection (Vero Cells) in the Treatment of Advanced Solid Tumors

Brief Summary

This phase I study evaluates the safety and efficacy of OH2 as single agent or in combination with Keytruda, an anti-PD-1 antibody, in patients with malignant solid tumors (Melanoma).

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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumor
• Melanoma

Intervention

• Biological: OH2 injection
  Oncolytic Type 2 Herpes Simplex Virus
• Drug: Keytruda
  Anti-PD-1 antibody
  Other Name: pembrolizumab

Study Arms

Experimental: Dose expansion

Dose expansion trial comprises of 2 cohorts. In cohort 1, OH2 injection will be administered at 1x10e7CCID50/mL . In cohort 2, OH2 injection will be administered at 1x10e7CCID50/mL in combination with Keytruda injection, an anti-PD-1 antibody, and the first doses of the two anti-tumor agents will be administered on the same day.

Interventions:

• Biological: OH2 injection
• Drug: Keytruda

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 11, 2020): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 13, 2023
• Estimated Primary Completion Date: March 13, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. The non-operative stage III or stage IV malignant tumor patients with clear diagnosis by pathology and/ or cytology; breast cancer, gastrointestinal adenocarcinoma, liver cancer, cervical cancer, malignant melanoma, head and neck tumors, Priority inclusion in soft tissue sarcomas (mainly for melanoma patients at the dose extension phase).
2. The absence of a conventional effective treatment or treatment failure or recurrence by a conventional method.
3. Male or female patients, aged 18 ≤ 75 years (including boundary value), general physical condition score ECOG 0 ≤ 1, expected survival time more than 3 months.
4. Prior anti-tumor treatment (including endocrine, chemical/ radiotherapy,targeted therapy) was over 4 weeks (more than 6 weeks of discontinuation using nitroso-and mitomycin-based chemotherapy) and was recovered to grade 1 from the side effects of prior treatment.
5. Those who have undergone major surgery will have to undergo surgery for four weeks.
6. There is at least one measurable lesion that is suitable for intratumoral injection. According to RECIST version 1.1, it is determined that at least once the CT or MRI examination shows the tumor lesion, it is possible to measure the tumor focus. The measured tumor focus is defined as the longest diameter ≥ 10 mm and the scanning thickness is not more than 5.0 mm. For lymph node lesions, the short diameter is ≥ 15 mm.
7. There is no serious dysfunction of the main organs.
8. (a) WBC≥3.0×109／L，ANC≥2.0×109／L ，PLT≥100×109／L，Hb≥90 g/L； (b) BUN and Scr. were in the upper limit of 1.5 times of the normal value; (c) TBIL≤ 1.5 times the upper limit of the normal value. (d) ALT and AST ≤ 2.5 times the upper limit of normal value; The value of patients with liver metastasis did not exceed 5 times the upper limit of normal value. (e) Coagulation function is normal (PT and APPT are within 1.5 times of the upper limit of normal value).
9. Female subjects and their spouses received effective contraceptives during and within 3 months of treatment.
10. Subjects with herpes in the reproductive organs needed three months after the end of herpes.
11. The informed consent was voluntarily signed and the expected compliance was good.

Exclusion Criteria:

1. Severe medical diseases, including severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, severe infection, active digestive tract ulcer, abnormal immune function (including, but not limited to, rheumatoid arthritis, lupus erythematosus, Sjogren's syndrome, etc.).
2. History of primary grape-film melanoma or other malignant tumors in the 3 years prior to treatment. (use of combination drugs only)
3. Past or present immunodeficiency diseases. (use of combination drugs only)
4. Treated with PD-1/PD-L1 or PD-L2 monoantigens or inhibitors that have been used or used in the past. (use of combination drugs only)
5. Autoimmune diseases requiring systemic treatment (e.g. steroids or immunosuppressants) during the first 2 years of treatment, such as autoimmune pneumonia, glomerular nephritis, vasculitis and other symptoms of autoimmune diseases; Except for wind or child asthma. (use of combination drugs only)
6. Have uncontrolled primary or brain metastatic tumors.
7. Suffering from uncontrolled mental illness, infectious diseases.
8. The lesions cannot meet the requirements of injection capacity in the tumor body.
9. Pregnant or lactating women.
10. Other experimental therapies or antiviral therapy are used or are being used within 4 weeks of treatment.
11. Other clinical studies have been taken in the past 4 weeks.
12. Allergy to herpes virus and drug ingredients.
13. The researchers believe that there is any reason why the patient is not suitable to participate in this trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jun Guo, PH.D; 86-010-88140650; guoj307@126.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04386967
• Other Study ID Numbers: OH2-I-ST-01
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Binhui Biopharmaceutical Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Binhui Biopharmaceutical Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Binhui Biopharmaceutical Co., Ltd.
• Verification Date: April 2022