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

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

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