OH2 plus HX008 for melanoma

Phase Ib Study of the Combination Use of Recombinant Human GM-CSF Type II Herpes Simplex Virus (OH2) Injection (Vero Cells) and HX008 Injection in the Treatment of Melanoma

This trial will test whether injecting the oncolytic virus OH2 together with the anti‑PD‑1 antibody HX008 helps people with advanced melanoma who have already received prior treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Binhui Biopharmaceutical Co., Ltd. (industry)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT04616443 on ClinicalTrials.gov

What this trial studies

This phase Ib trial combines intratumoral OH2, an engineered oncolytic herpes simplex virus that expresses GM‑CSF, with intravenous HX008, an anti‑PD‑1 antibody, to study safety and signs of anti‑tumor activity in melanoma. The study includes a dose‑escalation stage testing two OH2 dose levels and a dose‑expansion stage using the higher dose with scheduled OH2 and HX008 administrations. Patients will undergo regular radiologic imaging and clinical visits to measure objective response rate, progression‑free survival, and overall survival, while blood and swabs will monitor for virus shedding and immune markers. The design focuses on patients with injectable measurable lesions and prior progression on standard therapies, including prior PD‑1 therapy.

Who should consider this trial

Good fit: Adults with non‑operable stage III or stage IV melanoma, ECOG ≤1, expected survival >3 months, prior standard treatments failed (including prior PD‑1 therapy), and at least one measurable lesion suitable for intratumoral injection (≥5 mm).

Not a fit: Patients without injectable lesions, with poor performance status, symptomatic or untreated brain metastases, or who cannot tolerate prior treatment washout periods are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could improve tumor shrinkage and extend progression‑free and overall survival for patients with advanced melanoma who have progressed on prior treatments.

How similar studies have performed: Other oncolytic virus combinations with checkpoint inhibitors (for example talimogene laherparepvec plus anti‑PD‑1 agents) have shown promising responses in early‑phase trials, supporting this combination approach.

Eligibility criteria

Inclusion Criteria:

1. The non-operative stage III or stage IV malignant tumor patients with clear diagnosis by pathology.
2. Patients who have failed in conventional treatment (including PD-1 monotherapy) (disease progression or intolerance) or who have failed in previously assisted PD-1 monotherapy (last assisted PD-1 treatment relapse or metastasis within 6 months).
3. Patients with Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 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. There is at least one measurable lesion that is suitable for intratumoral injection. The measured tumor focus is defined as the longest diameter ≥ 5 mm.
6. Asymptomatic central nervous system metastasis, or treated asymptomatic brain metastasis patients, must be examined by a computerized fault scan (CT) or MRI for disease-free progression, stable for at least 3 months, and at least 4 weeks without steroid medication.
7. (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).
8. Female subjects and their spouses received effective contraceptives during and within 3 months of treatment.
9. Subjects with herpes in the reproductive organs needed three months after the end of herpes.
10. 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. Significant surgery is expected to be performed during the 28-day screening period during the study period.
3. Patients had active infections or unexplained fevers (over 38.5℃)during screening and before the first drug use.
4. Past or present immunodeficiency diseases.
5. The lesions do not meet the requirements of injection capacity(1ml) in the tumor body.
6. Pregnant or lactating women.
7. Other experimental therapies or antiviral therapy are used or are being used within 4 weeks of treatment.
8. Allergy to herpes virus and drug ingredients.
9. History of primary grape-film melanoma or other malignant tumors in the 5 years prior to treatment.
10. History of tuberculosis, or have tuberculosis at the time of screening.
11. Suffering from sudden lung disease, intersex lung disease, intersex pneumonia, pulmonary fibrosis, acute lung disease, radioactive pneumonia etc.
12. Patients with active autoimmune diseases or with a history of autoimmune diseases that may relapse, except for:

    1. Type I diabetes with stable condition after taking a fixed dose of insulin;
    2. Hypothyroidism;
    3. Controlled celiac disease;
    4. Skin diseases that do not require systemic treatment;
    5. Any other disease that does not re-occur without external triggers.
13. 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.
14. The researchers believe that there is any reason why the patient is not suitable to participate in this trial.

Where this trial is running

Beijing, Beijing Municipality

• Peking University Cancer Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: JUN GUO, PHD

Conditions: Melanoma, Oncolytic Virus