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

The University of Chicago

Status and phase

Withdrawn

Phase 1

Conditions

Malignant Pleural Mesothelioma (MPM)

Treatments

Biological: Multipeptide vaccine S-588210

Study type

Interventional

Funder types

Other

Identifiers

NCT02661659

IRB14-1519

Details and patient eligibility

About

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.

Full 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:

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

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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