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

Phase 1

Withdrawn

• Conditions: Malignant Pleural Mesothelioma (MPM)
• Interventions: Biological: Multipeptide vaccine S-588210

• Registration Number: NCT02661659
• Lead Sponsor: University of Chicago

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-01-20
• Study First Submitted QC: 2016-01-20
• Study First Posted: 2016-01-22
• Study Start: 2016-06-12
• Primary Completion: 2017-10-03
• Study Completion: 2017-10-03
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-07
• Last Update Posted: 2018-05-14

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Every other Week Vaccination	Multipeptide vaccine S-588210	Maintenance multipeptide vaccine (S-588210) administered every other week
Weekly Vaccination	Multipeptide vaccine S-588210	Maintenance multipeptide vaccine (S-588210) administered every week

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
6-month progression-free survival (PFS) rate	6 months
Peptide-specific cytotoxic T lymphocyte response determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay	At 2, 3, 4, 6 and 8 months of vaccination
Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03	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)	6 months

Trial Locations

Locations (1)

University of Chicago; 🇺🇸 Chicago, Illinois, United States