A Vaccine (Galinpepimut-S) with Nivolumab for the Treatment of Patients with WT1-Expressing Malignant Pleural Mesothelioma

Status: Active

Description

This phase I trial studies the side effects of a vaccine, galinpepimut-S, and nivolumab in treating patients with WT1 positive malignant pleural mesothelioma. Vaccines, such as galinpepimut-S, are made from Wilms Tumor Protein 1 (WT1) peptide and may help the body build an effective immune response to kill tumor cells that express WT1. Galinpepimut-S is mixed with a substance called montanide, which helps to boost the immune reaction to galinpepimut-S. The mixture of the galinpepimut-S and montanide make up the actual final vaccine that is then given to patients. Immunotherapy with monoclonal antibodies, such as nivolumab, may remove signals that block the immune system’s activity, indirectly strengthening the immune system to help fight the cancer. It has been shown that cancer vaccines can sometimes increase these signals that actually block the immune system’s anti-cancer activity. Using a cancer vaccine (galinpepimut-S) directed to mesothelioma cells with a drug that can unblock these negative signals (nivolumab) may help treat malignant pleural mesothelioma.

Eligibility Criteria

Inclusion Criteria

  • Karnofsky performance status >= 70%
  • Pathologic diagnosis of malignant pleural mesothelioma at Memorial Sloan Kettering (MSK)
  • Positive immunohistochemical staining for WT-1
  • Patients must have received at least one prior course of pemetrexed-based chemotherapy
  • Patients of childbearing potential must have a negative serum pregnancy test within 24 hours of receiving the first treatment on the study (if female) and must be practicing an effective form of birth control for the entire duration of treatment (both females and males)
  • Adequate archival or fresh tissue for correlative analyses within 60 days prior to starting treatment as long as there was no interval cancer-directed therapy
  • If sufficient archival or fresh tissue is not available, then a repeat biopsy at baseline prior to starting study treatment will be required

Exclusion Criteria

  • Pregnant or lactating women
  • Prior receipt of checkpoint inhibition
  • Patients with known active hepatitis B or known active hepatitis C virus
  • Patients with a serious unstable medical illness or another active cancer
  • Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Autoimmune disease requiring treatment with systemic steroids in the past 2 years
  • Current use of systemic corticosteroids at doses greater than prednisone 10 mg daily or the equivalent
  • Patients with active pneumonitis
  • Absolute neutrophil count >= 1000/mcL
  • Total bilirubin =< 1.5 mg/dl
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x upper limits of normal
  • Creatinine =< 1.5 x upper limits of normal

Locations & Contacts

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Marjorie G. Zauderer
Phone: 646-888-4656
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Marjorie G. Zauderer
Phone: 646-888-4656

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Marjorie G. Zauderer
Phone: 646-888-4656
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Marjorie G. Zauderer
Phone: 646-888-4656
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Marjorie G. Zauderer
Phone: 646-888-4656
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Marjorie G. Zauderer
Phone: 646-888-4656

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To assess the tolerability of galinpepimut-S combined with nivolumab in patients with previously treated malignant pleural mesothelioma (MPM).

SECONDARY OBJECTIVE:

I. To evaluate the immunogenicity of galinpepimut-S combined with nivolumab in patients with previously treated MPM by assessing the Wilms tumor (WT)1-specific cell-mediated immune response both peripherally and at the tumor site.

OUTLINE:

Patients galinpepimut-S mixed with montanide ISA 51 (montanide) VG subcutaneously (SC) on weeks 0, 2, 4, 6, 8, 10, 12, and 14, and nivolumab intravenously (IV) over 30 minutes on weeks 4, 6, 8, 10, 12, and 14 in the absence of disease progression or unacceptable toxicity. Patients also receive sargramostim SC on days -2 and 0 of weeks 0, 2, 4, 6, 8, 10, 12, and 14. Patients who do not have progressive disease at the end of 16 weeks receive galinpepimut-S mixed with montanide SC and nivolumab IV over 30 minutes starting at week 20. Treatment repeats every 2 weeks for up to 6 additional treatments (12 weeks) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 1 year.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Marjorie G. Zauderer

Trial IDs

Primary ID 17-654
Secondary IDs NCI-2019-05316
Clinicaltrials.gov ID NCT04040231