A Phase I Study With a Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Metastatic Melanoma

Xiangya Hospital of Central South University1 site in 1 country30 target enrollmentApril 21, 2020

ConditionsMelanoma (Skin)

InterventionsPeptide Anti-PD-1 rhGM-CSF Imiquimod 5% Topical Cream

DrugsPeptide Anti-PD-1 rhGM-CSF Imiquimod 5% Topical Cream

Overview

Phase: Phase 1
Intervention: Peptide
Conditions: Melanoma (Skin)
Sponsor: Xiangya Hospital of Central South University
Enrollment: 30
Locations: 1
Primary Endpoint: Number of Patients with Partial Response
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study assessed the safety and efficacy of individualized new antigen cancer vaccine combined with Programmed Cell Death Protein 1（PD1） inhibitor Toripalimab in the treatment of metastatic cutaneous melanoma. Melanoma is the most malignant skin neoplasm. Immunotherapy is the main treatment at present. PD1 is an immunological checkpoint and the inhibitors can reduce the immune escape of tumors, enhance T cell function and kill tumors. At present, PD1 antibody is the representative drug of immunotherapy, but the overall efficiency of its single drug treatment of acral melanoma is still low, and the combined treatment can significantly improve the efficiency. Melanoma has a high mutation load, which makes each patient have mutations specific to individual patients and tumors (changes in genetic material). These mutations lead to tumour cells producing proteins that are distinct from those of the body's own cells. These proteins used in vaccines may cause a strong immune response, which may help participants' bodies fight against any cancer cells that may lead to future recurrence of melanoma. Inhibition of PD1 can enhance the activity of T cells and form T cells with sustained killing activity. Tumor vaccines activate human Antigen Presenting Cells (APC) by injecting tumor antigens and adjuvants, and then activate T cells by APC to produce specific killing T cells. Therefore, the combination of "tumor vaccine + PD1 inhibitor" can produce effective specific killing and sustained activation of T cells, and prevent the establishment of inhibitory tumor microenvironment by tumor cells. The study will examine the safety and efficiency of the combined therapy at different time points and assess whether there is an immune response in the patient's peripheral blood and tumor tissue.

Registry

clinicaltrials.gov

Start Date

April 21, 2020

End Date

September 1, 2022

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Xiangya Hospital of Central South University

Responsible Party

Principal Investigator

pfkchenxiang

Chen Xiang, Principal Investigator，Clinical Professor，Vice-President

Xiangya Hospital of Central South University

Eligibility Criteria

Inclusion Criteria

•Patients must meet the following criteria on screening examination to be eligible to participate in the study:
•Patient is willing and able to give written informed consent.
•Age ≥ 18 years, ≤75 years
•Pathologically confirmed, clinically evident (by physical examination or radiographic imaging) stage IIIDN3c、IVM1a、M1b、M1c cutaneous melanoma.
•Lesions that can be measured，and at least one lesion that can be used to evaluate the efficacy of immunotherapy;Multiple biopsies are available for lesions.
•Patient is agreeable to allow tumor、normal tissue samples and blood samples to be submitted for genomic/complete exome/transcriptional sequencing；
•ECOG score is 0 or 1
•Life expectancy \>6 months
•Normal organ and bone marrow function as defined below:
•Leukocytes ≥ 3,500/mcL Absolute lymphocyte count \> 800/mcL Absolute neutrophil count \> 1,500/mcL Platelets \> 100,000/mcL Hemoglobin \> 10.0 g/dL Total serum bilirubin \< 1.0 x institutional upper limit of normal AST (SGOT)/ALT (SGPT) \< 2.0 x institutional upper limit of normal Serum creatinine\< 1.5 x institutional upper limit of normal

Exclusion Criteria

•Patients who meet any of the following criteria will not be eligible for this study.
•Uveal or mucosal melanoma；
•Patients who received immunotherapy or other targeted cancer therapy within 4 weeks (including, but not limited to: IL-2, CTLA-4 blockade, PD-1/PD-L1 blockade, but exception of INF-α given as adjuvant treatment)
•Previous bone marrow or stem cell transplant
•History of severe allergic reactions attributed to any vaccine therapy
•Active, known, or suspected autoimmune disease with the exception of vitiligo, type 1 diabetes, or psoriasis not requiring systemic treatment.
•Use of a non-oncology vaccine therapy for prevention of infectious diseases (up-to) 4 weeks prior to enrollment to the study. Patients may not receive any non-oncology vaccine therapy during the period of NeoVax administration and until at least 8 weeks after the last dose of study therapy
•In an immunosuppressive stage or immunosuppressive drugs were used systematically within 2 weeks.
•Patients with long-term use of glucocorticoids or with experimental anti-tumor drugs
•Active bacterial or fungal infections identified clinically (\>= level 2 of NCI-CTC edition 3);

Arms & Interventions

Intervention/Treatment

Personalized NeoAntigen Cancer Vaccine- Neo-Vac-Mn (peptides + rhGM-CSF+anti-PD1+Imiquimod 5% Topical Cream) NeoAntigen peptides:4 x 2 mg the total peptides given on days 84，87，91，98，105，133，and 161 Anti-PD-1 Toripalimab: 3mg/kg, ivgtt, Q2w rhGM-CSF: 3μg/kg given on Days 81，82，83，95，96，97，102，103，104，130，131，132，158，159，and 160 Imiquimod 5% Topical Cream:topical application on the injection site 6 hours before each NeoAntigen peptides injection

Intervention: Peptide