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

NCT04197882 | Unknown Phase 1

• 1 other identifier: OrienX010-II-12
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Keywords

complete resectable; melanoma; neoadjuvant treatment

Outcome Measures

Primary Outcomes (2)

• pathological response rates

  pCR and Major PR/Near pCR rates

  12 week of treatment

• Clinical effective rate

  objective response rates based on RECIST 1.1, include CR,PR,SD

  12 week of treatment

Secondary Outcomes (5)

• RFS

  1-year and 2-year after surgery

• OS

  approximate 3 years

• the safety of OrienX010 in combination with Toripalimab

  From date of enrolling to 90 days after end of treatment

• The surgical operation related events were observed

  Surgical treatment period

• Clinical effective rate

  12 week of treatment

Study Arms (1)

treatment

EXPERIMENTAL

This study consisted of 3 stage of neoadjuvant treatment, surgical, and adjuvant treatment. Neoadjuvant treatment period: OrienX010 intratumoral injection in combination with Toripalimab infusion. Toripalimab : 3 mg/kg, IV infusion: Once every 2 weeks for 6 doses ; OrienX010: Maximum injection volume 8 × 108 pfu, intratumoral injection: Once every 2 weeks for 6 doses ; Surgical treatment period: 2 weeks after the last dose of neoadjuvant treatment (± 7 days), the investigator designed the surgical protocol of the melanoma radical surgery according to the patient's individual disease, and performed postoperative care according to the patient's condition. Adjuvant treatment period: 3 weeks after operation (± 7 days), the patient was given Toripalimab infusion. Toripalimab 3 mg/kg intravenously given every 3 weeks (every 3 weeks per cycle) for up to 1 year (the one-year duration will be counted from 1st dose in neoadjuvant treatment).

Biological: OrienX010 Combination with Toripalimab injection

Interventions

OrienX010 Combination with Toripalimab injection BIOLOGICAL

OrienX010 Produced by Oriengene Biotechnology Co.,Ltd. Strength: 1.0 mL/vial. Toripalimab infusion Produced by Junshi Biosciences Co., Ltd. Strength: 240 mg/6 mL/vial; Sterile water injection dosage form; Expiry date: 24 months; Date of manufacture: Based on the date of manufacture indicated in the product package.

Also known as: Recombinant Human GM-CSF Herpes Simplex Virus intratumoral Injection combination with Recombinant Human Anti-PD-1 Monoclonal Antibody infusion

treatment

Eligibility Criteria

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

You may qualify if:

• An ICF approved by the Ethic Committee will voluntarily signed by the patient prior to initiating any screening or specific study procedures;
• Male or female patients between 18 and 75 years of age;
• 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).
• Patients with ECOG performance status of 0 or 1;
• 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;
• \. 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.

You may not qualify if:

• 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;
• Patients with negative anti-herpes simplex virus type I (HSV-1) antibodies IgG and IgM ;
• The patient's lesion does not meet the requirement of the intratumoral injection volume or is not suitable for intratumoral injection;
• Received anti-herpes simplex virus therapy (such as aciclovir, ganciclovir, valaciclovir, and arabinoside) within 4 weeks prior to the first dose of study treatment;
• 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) ;
• 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;
• Patients with known hypersensitivity to the study drug, its active ingredient, excipients;
• Patient with HBsAg positive and HBV DNA copies \> 1×103copies/mL;
• Patients with positive hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies;
• 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;
• 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;
• 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
• Tumor's macrovascular invasion in the iliac and femoral vessels;
• 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;
• Within 30 days of screening, the patient had received any other study product or had participated in another intervention clinical trial;

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (1)

• Liu J, Wang X, Li Z, Gao S, Mao L, Dai J, Li C, Cui C, Chi Z, Sheng X, Lai Y, Tan Z, Lian B, Tang B, Yan X, Li S, Zhou L, Wei X, Li J, Guo J, Si L. Neoadjuvant oncolytic virus orienx010 and toripalimab in resectable acral melanoma: a phase Ib trial. Signal Transduct Target Ther. 2024 Nov 22;9(1):318. doi: 10.1038/s41392-024-02029-2.

  PMID: 39572525 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jun Guo, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of department of renal cancer and melanoma

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 13, 2019
• Study Start: May 27, 2019
• Primary Completion: May 27, 2021
• Study Completion: May 27, 2025
• Last Updated: February 10, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)