Study of Oncolytic Virus in Combination With HX-008 and Axitinib in Melanoma Patients With Liver Metastasis

NCT05070221 | Unknown Phase 1

• 1 other identifier: BH-OH2-014
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Malignant melanoma, is a kind of malignant tumor derived from melanocytes. It is common in skin, mucous membrane, eye choroid and other parts. Melanoma is one of the fastest growing malignant tumors with an annual incidence rate of 3-5%. In 2012, there were 232000 new cases of melanoma and 55000 deaths worldwide. Though, the incidence rate of melanoma is relatively low in China, it has been increasing rapidly in recent years. Melanoma has seriously endangering the health of Chinese people. Patients with stage Ⅳ melanoma have a poor prognosis. According to statistics, the median survival time of stage M1a melanoma is 15 months, while stage M1b is 8 months. The median survival time of bone metastasis melanoma is 6 months, while liver and brain metastasis is 4 months. The overall median survival time of metastatic melanoma is only 7.5 months, and the 2-year survival rate is 15%. For patients with advanced melanoma, dacarbazine is the only chemotherapy drug approved by NMPA, but its overall effective rate is only 13.4%, and the median survival time is 5.6 \~ 11 months. Therapies(new drugs or new combination treatments)with higher remission rate and longer survival are urgently needed for patients with advanced melanoma.

Conditions

Melanoma Stage IV

Outcome Measures

Primary Outcomes (1)

• ORR(6 months)

  ORR(6 month) is defined as the proportion of subjects with complete response (CR) and partial response (PR) after 6 months of treatment.

  From first dose up to 6 months, approximately.

Secondary Outcomes (5)

• DCR(6 months)

  Time Frame: From first dose up to 6 months, approximately.

• PFS

  From first dose up to 12 months, approximately.

• OS

  From first dose up to 12 months, approximately.

• overall survival rate（one year）

  From first dose up to 12 months, approximately.

• overall survival rate（two years）

  From first dose up to 24 months, approximately.

Study Arms (2)

Arm A

EXPERIMENTAL

Patients histologically confirmed mucosal melanoma will get OH2 （once every two weeks）and HX-008 (once every three weeks)and Axitinib (once every day).

Drug: Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF); Drug: Recombinant humanized anti-PD-1 monoclonal antibody for injection; Drug: Axitinib

Arm B

EXPERIMENTAL

Patients histologically confirmed non-mucosal melanoma will get OH2 （once every two weeks）and HX-008 (once every three weeks)and Axitinib (once every day).

Drug: Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF); Drug: Recombinant humanized anti-PD-1 monoclonal antibody for injection; Drug: Axitinib

Interventions

Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF) DRUG

less than 8mL/time，Q2W，i.t.；

Also known as: OH2

Arm A; Arm B

Recombinant humanized anti-PD-1 monoclonal antibody for injection DRUG

200mg/time，Q3W，i.v.；

Also known as: HX-008

Arm A; Arm B

Axitinib DRUG

5mg，bid，p.o.；

Also known as: Inlyta®

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Voluntarily sign Informed Consent Form（ICF）, understand the study, be willing to follow and be able to complete all test procedures;
• Male and female, 18-75 years old (including boundary value);
• Histologically confirmed stage IV melanoma with liver metastasis who lacks or becomes refractory to standard treatment;
• Eastern Cooperative Oncology Group (ECOG) Performance Status is 0 or 1;
• Expected survival at least 3 months;
• The interval between the first administration and previous treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy and biotherapy for melanoma) in the past is over 4 weeks, and has recovered to grade 1 from the adverse reactions of previous treatment;
• At least one measurable or evaluable lesion;
• Liver metastasis has lesions suitable for intratumoral injection;
• Asymptomatic central nervous system metastasis or asymptomatic brain metastasis after treatment must be confirmed by CT / MRI that there is no disease progression, stable for at least 3 months, and no steroid treatment for at least 4 weeks;
• Appropriate organs and hematopoietic function according to the following laboratory tests: neutrophil absolute count (neut#) ≥ 2.0 × 109/L； Absolute white blood cell count (WBC) ≥ 3.0 × 109/L； Platelet ≥ 100 × 109/L； Hemoglobin ≥ 90g / L; Serum creatinine ≤ 1.5 times the upper limit of normal value (ULN); AST and alt ≤ 5 times ULN; Serum total bilirubin (TBIL) ≤ 1.5 times ULN; International normalized ratio (INR) ≤ 1.5 times ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 times ULN (except for patients undergoing anticoagulant therapy);
• Male patients and female subjects of childbearing age should agree to take effective contraceptive measures from the signing of informed consent to 3 months after the last administration;
• Patients with herpes need 3 months after the end of herpes treatment.

You may not qualify if:

• Patients with a history of primary uveal melanoma or any other (including unknown primary) malignancy within 5 years before the first administration of the trial treatment.
• Note: 1 or 2 stage skin basal / squamous cell carcinoma, superficial bladder cancer or orthotopic carcinoma receiving potentially curative treatment are the most effective treatments;
• Liver lesions are not suitable for intratumoral injection or do not meet the injection volume requirements;
• Patients who had received anti herpes simplex virus treatment within 4 weeks before the first administration of the trial treatment, such as acyclovir, ganciclovir, valacyclovir, arabine adenosine, etc;
• Patients with active or history of autoimmune diseases that may recur (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc.), or patients with high risk (such as organ transplantation and immunosuppressive treatment). However, subjects with the following diseases are allowed to be included in the group:
• stable type 1 diabetic patients after a fixed dose of insulin.
• autoimmune hypothyroidism or Hashimoto's thyroid inflammation requiring only hormone replacement therapy;
• skin diseases that do not require systemic treatment (such as eczema, skin rash accounting for less than 10% of the body surface, psoriasis without ophthalmic symptoms, etc.);
• celiac disease that has been controlled;
• any other disease that will not recur without external inducing factors;
• Patients with major surgery are expected to include a 28 day screening period during the study period;
• Patients requiring systemic corticosteroids (equivalent to \> 10mg prednisone / day) or other immunosuppressive drugs within 14 days before enrollment or during the study. However, you are allowed to join the group under the following conditions:
• subjects were allowed to use topical or inhaled glucocorticoids;
• allow short-term (≤ 7 days) use of glucocorticoids to prevent or treat non autoimmune allergic diseases;
• Patients with active gastrointestinal ulcer, incomplete intestinal obstruction, active gastrointestinal bleeding and perforation;

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

MeSH Terms

Conditions

Melanoma

Interventions

Injections; Axitinib

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

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Jun Guo, MD

CONTACT

86-10-88121122; guoj307@126.com

Chuanliang Cui, MD

CONTACT

1008ccl@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: October 7, 2021
• Study Start: October 1, 2021
• Primary Completion: October 31, 2023
• Study Completion: December 31, 2023
• Last Updated: October 7, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share