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
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.
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
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
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
Secondary Outcome
Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Condition
Malignant Pleural Mesothelioma (MPM)
Intervention
Multipeptide vaccine S-588210
Study Arms / Comparison Groups
Weekly Vaccination
Description: Maintenance multipeptide vaccine (S-588210) administered every week
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
0
Start Date
June 12, 2016
Completion Date
October 3, 2017
Primary Completion Date
October 3, 2017
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02661659
Organization ID
IRB14-1519
Responsible Party
Sponsor
Study Sponsor
University of Chicago
Study Sponsor
, ,
Verification Date
May 2018