Mesothelioma.com Resources for Patients and their Families

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

Brief Summary

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.

Tracking Information
First Received DateJanuary 20, 2016
Last Changed DateMay 10, 2017
Start DateJune 2016
Anticipated Primary Completion DateFebruary 2018
Primary Outcome Measures

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]

Secondary Outcome Measures

Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03 [Time Frame: Up to 4 weeks]

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]

6-month progression-free survival (PFS) rate [Time Frame: 6 months]

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]

Descriptive Information
PhasePhase 1
Study TypeInterventional
Condition
  • Malignant Pleural Mesothelioma (MPM)
Intervention
  • Biological: Multipeptide vaccine S-588210
Study Arms / Comparison Groups2 / 0
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

Recruitment Information
Recruitment StatusWithdrawn
Actual Enrollment0
GenderAll
Ages18 Years - N/A
Accepts Healthy VolunteersNo
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

Administrative Information
NCTIDNCT02661659
Responsible Party,
SponsorUniversity of Chicago
Verification DateMay 2017
Mesothelioma Doctors by State
  • Breaking News
  • Emerging Clinical Trials
  • Delivered within 24 hrs

Yes   No

Mesothelioma Cancer Alliance Blog

FEATURED CONTENT:


RECENT POSTS:

Remembering Mesothelioma Victims in the UK

The Challenges of Research in Immunotherapy

The Importance of Cancer Research in Immunotherapy

Mesothelioma Treatment Guide

Free Mesothelioma Treatment Guide

Please fill in the form below to request our FREE Mesothelioma Treatment Guide. It will be sent to you within 24 hours.

Have you or someone you know been diagnosed with mesothelioma?

Get Access To: