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

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.

Study Overview

• Status: Withdrawn
• Conditions: Malignant Pleural Mesothelioma (MPM)
• Intervention / Treatment: Biological: Multipeptide vaccine S-588210

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 Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Weekly Vaccination; Maintenance multipeptide vaccine (S-588210) administered every week	Biological: Multipeptide vaccine S-588210
Other: Every other Week Vaccination; Maintenance multipeptide vaccine (S-588210) administered every other week	Biological: Multipeptide vaccine S-588210

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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
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

Collaborators and Investigators

• Sponsor: University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2016
• Primary Completion (Actual): October 3, 2017
• Study Completion (Actual): October 3, 2017

Study Registration Dates

• First Submitted: January 20, 2016
• First Submitted That Met QC Criteria: January 20, 2016
• First Posted (Estimate): January 22, 2016

Study Record Updates

• Last Update Posted (Actual): May 14, 2018
• Last Update Submitted That Met QC Criteria: May 7, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: mesothelioma; S-588210; multipeptide vaccine
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant
• Other Study ID Numbers: IRB14-1519