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A Phase Ib Trial of a Maintenance Multipeptide Vaccine (S-588210) in Patients With Unresectable Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy

NCT02661659

Description:

A phase Ib study investigating the safety, the immunogenicity and the optimal administration frequency of the S-588210 5-peptide vaccine in MPM patients without progression after pemetrexed-based chemotherapy will be conducted. Additionally, to identify more accurate predictive biomarkers of response to S-588210, T-cell-receptor-sequencing (TCR) pre- and post-vaccination will be performed in blood samples of patients treated with the vaccine. Immunohistochemical analysis of the vaccine oncoantigens will also be correlated with induction of antigen-specific T-cell responses. Finally, to explore the infiltration of tumors with T-cells and the potential presence of an immunosuppressive tumor microenvironment, immunohistochemistry for immune checkpoints (including PDL1/PD1, CTLA4) and immune suppressive cell subsets (T-regs, macrophages) will be performed.

Related Conditions:
  • Malignant Pleural Mesothelioma
Recruiting Status:

Withdrawn

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title:A Phase Ib Trial of a Maintenance Multipeptide Vaccine (S-588210) in Patients With Unresectable Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy
  • Official Title:A Phase Ib Trial of a Maintenance Multipeptide Vaccine (S-588210) in Patients With Unresectable Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: IRB14-1519
  • NCT ID: NCT02661659

Trial Conditions

  • Malignant Pleural Mesothelioma (MPM)

Trial Interventions

DrugSynonymsArms

Trial Purpose

A phase Ib study investigating the safety, the immunogenicity and the optimal administration frequency of the S-588210 5-peptide vaccine in MPM patients without progression after pemetrexed-based chemotherapy will be conducted. Additionally, to identify more accurate predictive biomarkers of response to S-588210, T-cell-receptor-sequencing (TCR) pre- and post-vaccination will be performed in blood samples of patients treated with the vaccine. Immunohistochemical analysis of the vaccine oncoantigens will also be correlated with induction of antigen-specific T-cell responses. Finally, to explore the infiltration of tumors with T-cells and the potential presence of an immunosuppressive tumor microenvironment, immunohistochemistry for immune checkpoints (including PDL1/PD1, CTLA4) and immune suppressive cell subsets (T-regs, macrophages) will be performed.

Detailed Description

Primary Objective:

To evaluate the rate of peptide-specific CTL induction to S-588210 within the first 8 months in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy treated on a weekly or every other week vaccination schedule.

Secondary Objectives:

1. To evaluate the safety of S-588210 in HLA-A*02:01-positive patients with MPM treated with S-588210

2. To determine the disease control rate (DCR) in HLA-A*02:01-positive patients with MPM treated with S-588210

3. To determine the progression-free-survival (PFS) in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy and who are treated with S-588210

4. To evaluate the peptide-specific CTL response to S-588210 over time up to 8 months in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy

Trial Arms

NameTypeDescriptionInterventions
Weekly VaccinationOtherMaintenance multipeptide vaccine (S-588210) administered every week
    Every other Week VaccinationOtherMaintenance multipeptide vaccine (S-588210) administered every other week

      Eligibility Criteria

      Inclusion Criteria:

      - Patients with unresectable MPM that have completed 4-6 cycles of standard first-line pemetrexed-based chemotherapy for at least 1 month and have not progressed

      - Age>18

      - Able to provide informed consent for the study

      - HLA-A*02:01 positive

      - ECOG PS=0-1 at enrollment

      - Measurable indicator lesion by modified RECIST criteria

      - Adequate bone marrow (ANC > 1000cells/ml, PLT > 50,000/ml, Hg > 8gr/dL), renal (Cr > 2.5xUNL) and liver function (AST, ALT< 3x UNL, total bilirubin < 2x UNL, ALP < 3x UNL)

      - Archival tumor tissue available for IHC (1 paraffin-embedded block)

      - Epithelioid or biphasic histology

      Exclusion Criteria:

      - Chemotherapy or investigational antineoplastic drug within 1 month of planned initiation of vaccine therapy

      - Patients who received DEPDC1, MPHOSPH1, URLC10, CDCA1, or KOC1 peptide vaccines before

      - Active treatment with corticosteroids or other immunosuppressive agents

      - Patients who are expected to require any of the following therapies between enrollment and completion or discontinuation of the study treatment:

      1. immunosuppressive drugs, including corticosteroids, methotrexate, mercaptopurine, azathioprine, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, ATG (anti-thymoglobulin), IL2-receptor antibodies (basiliximab, daclizumab), TNF-a antibodies (infliximab, etanercept, adalimumab)

      2. radiotherapy for the target disease

      3. surgical therapy for the target disease

      - History of bone marrow transplantation

      - Active infection

      - Human immunodeficiency virus infection

      - History of or active systemic autoimmune disorder or immunodeficiency syndromes

      - History of severe (CTCAE v.4.03 grade 3 or higher) allergic reaction to a drug, vaccination, or biological preparation.

      - Pregnancy

      - Patients who cannot or do not intend to practice effective contraception

      - Severe illness requiring hospitalization

      - Lymphocytes <15% of total WBCs at baseline

      - Sarcomatoid histology

      - Severe (CTCAE v.4.03 grade 3 or higher) concurrent hepatic impairment, renal impairment, heart disease, hematological disease, respiratory disease, or metabolic disease

      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Both
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Proportion of patients who show in vitro cytotoxic T lymphocyte induction to at least 2 of the 5 antigens determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay
      Time Frame:Within 8 months from initiation of vaccination
      Safety Issue:No
      Description:

      Secondary Outcome Measures

      Measure:Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03
      Time Frame:Up to 4 weeks
      Safety Issue:Yes
      Description:
      Measure:Disease control rate defined as the proportion of patients who are assessed as having complete response (CR), partial response (PR), or stable disease (SD) (>3 months)
      Time Frame:6 months
      Safety Issue:No
      Description:
      Measure:6-month progression-free survival (PFS) rate
      Time Frame:6 months
      Safety Issue:No
      Description:
      Measure:Peptide-specific cytotoxic T lymphocyte response determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay
      Time Frame:At 2, 3, 4, 6 and 8 months of vaccination
      Safety Issue:No
      Description:

      Trial Keywords

      • mesothelioma
      • multipeptide vaccine
      • S-588210