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

NCT02661659 | Withdrawn Phase 1

• 1 other identifier: IRB14-1519
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Pleural Mesothelioma (MPM)

Keywords

mesothelioma; multipeptide vaccine; S-588210

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (2)

Weekly Vaccination

OTHER

Maintenance multipeptide vaccine (S-588210) administered every week

Biological: Multipeptide vaccine S-588210

Every other Week Vaccination

OTHER

Maintenance multipeptide vaccine (S-588210) administered every other week

Biological: Multipeptide vaccine S-588210

Interventions

Multipeptide vaccine S-588210 BIOLOGICAL

Every other Week Vaccination; Weekly Vaccination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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)
• radiotherapy for the target disease
• 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

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Mesothelioma, Malignant; Mesothelioma

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2016
• First Posted: January 22, 2016
• Study Start: June 12, 2016
• Primary Completion: October 3, 2017
• Study Completion: October 3, 2017
• Last Updated: May 14, 2018

Record last verified: 2018-05

Locations

US (1)