Clinical Study to Evaluate OrienX010 in Combination With Toripalimab as Neoadjuvant Treatment in Advanced Melanoma

An Open-Label, Phase Ib Clinical Study to Evaluate OrienX010 in Combination With Toripalimab as Neoadjuvant Treatment in the Patients With Complete Resectable Stage III and Stage IV (M1a) Melanoma

This study is an open-label, Phase Ib clinical study to evaluate recombinant human GM-CSF herpes simplex virus intratumoral injection (OrienX010) in combination with recombinant humanized anti-PD-1 monoclonal antibody infusion (Toripalimab) as neoadjuvant treatment in patients with complete resectable stage III and IV (M1a) melanoma.

This study is planned to enroll approximately 30 patients with stage III and IV melanoma (M1a) who meet protocol requirements.

This study is to evaluate the efficacy and safety of recombinant human GM-CSF herpes simplex virus intratumoral injection (OrienX010) in combination with recombinant humanized anti-PD-1 monoclonal antibody infusion (Toripalimab infusion) as neoadjuvant treatment in the patients with complete resectable stage III and IV (M1a) melanoma.

Inclusion Criteria:

1. An ICF approved by the Ethic Committee will voluntarily signed by the patient prior to initiating any screening or specific study procedures;
2. Male or female patients between 18 and 75 years of age;
3. Patients with definite diagnosis of complete resectable stage III and IV melanoma (M1a) based on histology and/or cytology, and with at least 1 measurable lesion(s).
4. Patients with ECOG performance status of 0 or 1;
5. Expected Survival> 4 months;

The patient has good function in each organ, and the following conditions are required at screening according to the laboratory reference range:

• White blood cell count ≥ 3.0 × 109/L;

• Absolute neutrophil value ≥ 1.5 × 109/L;

• Platelet count ≥ 100 × 109/L;

• Hemoglobin ≥ 90 g/L;

• Serum albumin ≥ 2.5 g/dL;

• Liver function tests: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN;

• Renal function tests: Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min at 24 hours (Cockcroft and Gault formula);

• International normalized ratio (INR) ≤ 1.5, and activated partial thromboplastin time (APTT) or partial prothrombin time (PTT) ≤ 1.5 × ULN;

  7. Female patients with childbearing potential (including premature menopause, menopausal < 2 years and non-surgical sterilization), male patients, and partners of male patients must agree to use effective contraception during the study: Surgical sterilization, oral contraceptives, intrauterine devices, sexual abstinence or barrier contraceptive combination spermicides; All patients must continue contraception for 6 months after the last treatment.

Exclusion Criteria:

1. Patients previously treated with T-VEC or similar; Patients previously treated with anti PD-1 antibody, anti PD-L1 antibody, anti PD-L2 antibody or similar;
2. Patients with negative anti-herpes simplex virus type I (HSV-1) antibodies IgG and IgM ;
3. The patient's lesion does not meet the requirement of the intratumoral injection volume or is not suitable for intratumoral injection;
4. Received anti-herpes simplex virus therapy (such as aciclovir, ganciclovir, valaciclovir, and arabinoside) within 4 weeks prior to the first dose of study treatment;
5. Received another anti-tumor monoclonal antibody (mAb) within 4 weeks prior to the first dose of study treatment or hasn't recover (≤ Grade 1) from adverse events due to prior therapy (occurring earlier than 4 weeks) ;
6. Patients with a history of other (including unknown primary) malignancies within 5 years prior to the first dose of trial treatment. Note: Except for fully treated stage 1 or 2 basal/squamous cell carcinoma of the skin, superficial bladder cancer, or in situ cancer that is treated with potentially curative therapy;
7. Patients with known hypersensitivity to the study drug, its active ingredient, excipients;
8. Patient with HBsAg positive and HBV DNA copies > 1×103copies/mL;
9. Patients with positive hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies;
10. Patients with any unstable systemic disease, including but not limited to: Serious infection, uncontrolled diabetes mellitus, unstable angina, cerebrovascular accident or transient cerebral ischemia, myocardial infarction, congestive heart failure, and serious arrhythmia liver, kidney, or metabolic disease requiring medical treatment;
11. patients with active CNS metastases. patients may participate in the study if their CNS is adequately treated and their neurological symptoms recover to levels less than or equal to Grade 1 (CTCAE) for at least 2 weeks before enrollment, with the exception of residual signs or symptoms associated with CNS therapy . In addition, patients must be those who do not use corticosteroids or who take stable doses of ≤ 10 mg prednisone/day (or equivalent dose) or who decrease to ≤ 10 mg prednisone/day;
12. Patients with autoimmune disease, received liver or other organs transplantation once before, active pulmonary tuberculosis; or patients received major surgical procedures, live vaccination, immunotherapy 4 weeks prior to study initiation
13. Tumor's macrovascular invasion in the iliac and femoral vessels;
14. The disease (e.g., mental illness, etc.) or condition (e.g., alcoholism or drug abuse, etc.) of the patient may increase the patient's risk of receiving trial medication or affect the patient's compliance with the study requirements, or may confuse the study results;
15. Within 30 days of screening, the patient had received any other study product or had participated in another intervention clinical trial;
16. Pregnant or lactating women, or women who are prepared to become pregnant or lactating during the study; Men or women who are unwilling to use effective contraception;
17. Other situations that the investigators think are not suitable for inclusion