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

Malignant Pleural Mesothelioma (MPM) Clinical Trial

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Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02661659
• Other study ID #: IRB14-1519
• Status: Withdrawn
• Phase: Phase 1
• Start date: June 12, 2016
• Est. completion date: October 3, 2017

Study information

• Verified date: May 2018
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 3, 2017
• Est. primary completion date: October 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Malignant Pleural Mesothelioma (MPM)
• Mesothelioma

Intervention

Biological:
• Multipeptide vaccine S-588210

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Within 8 months from initiation of vaccination
Secondary	Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03		Up to 4 weeks
Secondary	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)		6 months
Secondary	6-month progression-free survival (PFS) rate		6 months
Secondary	Peptide-specific cytotoxic T lymphocyte response determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay		At 2, 3, 4, 6 and 8 months of vaccination