Clinical Trials /

A Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Melanoma

NCT04072900

Description:

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.

Related Conditions:
  • Cutaneous Melanoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Melanoma
  • Official Title: A Phase I Study With a Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: XYM001
  • NCT ID: NCT04072900

Conditions

  • Melanoma (Skin)

Interventions

DrugSynonymsArms
PeptideNeoAntigen peptidesIntervention/Treatment
Anti-PD-1ToripalimabIntervention/Treatment
rhGM-CSFIntervention/Treatment
Imiquimod 5% Topical CreamIntervention/Treatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Intervention/TreatmentExperimentalPersonalized 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
  • Peptide
  • Anti-PD-1
  • rhGM-CSF
  • Imiquimod 5% Topical Cream

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must meet the following criteria on screening examination to be eligible to
             participate in the study:

          2. Patient is willing and able to give written informed consent.

          3. Age ≥ 18 years, ≤75 years

          4. Pathologically confirmed, clinically evident (by physical examination or radiographic
             imaging) stage IIIDN3c、IVM1a、M1b、M1c cutaneous melanoma.

          5. 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.

          6. Patient is agreeable to allow tumor、normal tissue samples and blood samples to be
             submitted for genomic/complete exome/transcriptional sequencing;

          7. ECOG score is 0 or 1

          8. Life expectancy >6 months

          9. 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

         10. Women of childbearing potential (WOCBP) must have a negative pregnancy test before
             entering the trial and within 7 days prior to start of study medication.

         11. Female patients enrolled in the study, short-term have no fertility plan and must
             agree to use an adequate method of contraception starting with the first dose of study
             therapy through 90 days after the last dose of study therapy.

         12. Male patients must agree to use an adequate method of contraception starting with the
             first dose of study therapy through 90 days after the last dose of study therapy.

         13. Good compliance, able to follow research protocols and follow-up procedures.

        Exclusion Criteria:

          1. Patients who meet any of the following criteria will not be eligible for this study.

          2. Uveal or mucosal melanoma;

          3. 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)

          4. Previous bone marrow or stem cell transplant

          5. History of severe allergic reactions attributed to any vaccine therapy

          6. Active, known, or suspected autoimmune disease with the exception of vitiligo, type 1
             diabetes, or psoriasis not requiring systemic treatment.

          7. 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

          8. In an immunosuppressive stage or immunosuppressive drugs were used systematically
             within 2 weeks.

          9. Patients with long-term use of glucocorticoids or with experimental anti-tumor drugs

         10. Active bacterial or fungal infections identified clinically (>= level 2 of NCI-CTC
             edition 3);

         11. Known chronic infections with HIV, hepatitis B or C

         12. Known active or latent tuberculosis infection

         13. A history of idiopathic pulmonary fibrosis and organized pneumonia, or active
             pneumonia on chest computed tomography.

         14. Complicated with other tumors, except for cervical cancer in situ and basal cell
             carcinoma five years ago.

         15. Severe coronary or cerebrovascular disease, or other diseases that the investigators
             considered should to be exclusion;

         16. Drug abuse, Clinical, psychological or social factor result in affecting informed
             consent or research implementation.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants experiencing adverse events
Time Frame:up to a maximum of 252 days
Safety Issue:
Description:Number of participants experiencing clinical and laboratory adverse events (AE)

Secondary Outcome Measures

Measure:Monitoring of cellular immune response
Time Frame:up to a maximum of 252 days
Safety Issue:
Description:the immune response of serum and tumor tissue

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Xiangya Hospital of Central South University

Trial Keywords

  • Melanoma, Metastasis

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