This phase Ib study evaluates the safety and efficacy of OH2 in combination with HX008, an anti-PD-1 antibody, in patients with 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.
The trial is a phase Ib study evaluating the safety and efficacy of OH2 injection combined with HX008 injection in patients with Melanoma. In the Phase Ib dose escalation trial, two doses (1x10e6, 1x10e7 CCID50/mL) of OH2 will be combined with HX008(at a fixed dose of 200mg) will be tested. In the Phase Ib dose expansion trial, OH2(1x10e7 CCID50/mL) will be injected individually in the first week, followed by every two weeks while HX008(200 mg) will be injected every three weeks after the first injection which will be in the second week. Blood samples will be collected and radiological imaging will be performed to evaluate safety and efficacy during the trial. Besides, patients will be subjected to cutaneous swabs, and blood/urine/feces sampling to determine virus shedding. Participating patients will be evaluated for objective response rate, progression free survival and overall survival.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Oncolytic Type 2 Herpes Simplex Virus
Recombinant humanized anti-PD-1 monoclonal antibody of injection
Peking University Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGEvaluation of dose-limiting toxicity (DLT) of OH2 injection in combination with HX008 injection in patients with melanoma
According to the version 5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events, the adverse events during the entire study period are evaluated to observe the dose-limiting toxicity.
Time frame: 21 days after treatment
The response rate of patients with melanoma receiving OH2 injection in combination with HX008 injection
Tumor evaluation is performed according to RECIST1.1 and iRECIST1.1.
Time frame: 18 months
The immunoreactivity of OH2 injection and HX008 injection.
Detection of increased systemic immune Response markers in peripheral blood mononuclear cells by flow cytometer.Detection of complement C3, C4 titer.
Time frame: 18 months
The immunogenicity of OH2 injection and HX008 injection.
The immunogenicity of OH2 is evaluated by detection of anti-HSV2 antibodies and anti-GM-CSF antibodies in the blood.The immunogenicity of HX008 is evaluated by detection of anti-PD-1 antibodies in blood by ADA.
Time frame: 18 months
The biodistribution and biologic effect of OH2 injection.
The biodistribution of OH2 injection as determined by the concentration of OH2 in blood, urine and feces of participating patients.The biologic effect of OH2 injection as determined by the GM-CSF RNA quantification in fine needle aspiration(FNA) of patients.Expression of GM-CSF in FNA.The original result unit is copies/ul.
Time frame: 18 months
The pharmacygenic dynamics (PK) characteristics of HX008 injections in the case of HX008 injections combined with OH2 injections.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Cmax.
Time frame: 18 months
Explore the changes in peripheral blood and tumor tissue immune-related indicators during treatment.
Peripheral blood T lymphocyte subtype.The ratio of CD4/CD8 in blood lymphocytes. PD-L1 expression in tumor tissue.
Time frame: 18 months