Galinpepimut-S (WT-1 Analog Peptide) Vaccine in Malignant Pleural Mesothelioma After Combined Modality Therapy

Randomized Phase II Study of Adjuvant WT-1 Analog Peptide Vaccine in Patients With Malignant Pleural Mesothelioma (MPM) After Completion of Combined Modality Therapy

Study of galinpepimut-S, a Wilms Tumor-1 (WT1) vaccine, to see if it delays or prevents the mesothelioma from growing back after surgery. WT1 is a protein in cancer cells that regulates gene expression and causes cell growth.

Study Overview

• Status: Completed
• Conditions: Malignant Pleural Mesothelioma
• Intervention / Treatment: Biological: Galinpepimut-S + Montanide + GM-CSF; Biological: Montanide + GM-CSF

Detailed Description

The doctors are testing galinpepimut-S, a Wilms Tumor-1 (WT1) vaccine, to see if it delays or prevents the mesothelioma from growing back after surgery. WT1 is a protein in cancer cells that regulates gene expression and causes cell growth. Mesothelioma tumors generally have high levels of WT1.This study was originally designed to have two treatment groups. One group received non-specific immunotherapy with medications called Montanide and Sargramostim (Granulocyte Macrophage Colony Stimulating Factor, GM-CSF). Enrollment to this group has stopped The other group, which continues receives more specific immunotherapy with galinpepimut-S plus Montanide and GM-CSF. Both Montanide and GM-CSF are commonly given along with vaccines because they have a general effect in boosting the immune response. Some researchers believe that this general increase in the immune system may have some effect in treating cancer. Some studies using GM-CSF with melanoma vaccines have suggested that it could lessen the effects of the vaccine. The addition of the WT1 proteins makes this therapy more directed to mesothelioma. The combination of galinpepimut-S with Montanide and GM-CSF has been tested in a prior trial including 9 patients with advanced mesothelioma. In that trial, the vaccine was safe and caused an immune response.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologic diagnosis of malignant pleural mesothelioma (MPM) confirmed at participating institution.
• Positive immunohistochemical staining for WT-1 (greater than 10% of cells).
• Completion of multimodality therapy. This must include surgical resection by either pleurectomy/decortication or extrapleural pneumonectomy. The surgery should be performed with the intent of complete resection, though patients with an R1 resection will still be eligible. Patients should have also received treatment with chemotherapy and/or radiation. Patients with an R2 resection are also eligible as long as the site of residual disease is treated post-operatively with radiotherapy.
• 4-12 weeks since completion of combined modality therapy.
• Age > or = to 18 years
• Karnofsky performance status > or = to 70%
• Hematologic parameters: Absolute neutrophil count > or = to 1000/mcL, Platelets > or = to 50K/mcL.
• Biochemical parameters: Total bilirubin < or = to 2.0 mg/dl, AST and ALT < or = to 2.5 x upper limits of normal, Creatinine < or = to 2.0 mg/dl.

Exclusion Criteria:

• Pregnant or lactating women.
• Patients with active infection requiring systemic antibiotics, antiviral, or antifungal treatments.
• Patients with a serious unstable medical illness or another active cancer.
• Patients taking systemic corticosteroids.
• Patients with an immunodeficiency syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Galinpepimut-S + Montanide + GM-CSF; Galinpepimut-S emulsified with Montanide adjuvant (1:1 ratio) 1 mL and GM-CSF 70 mcg	Biological: Galinpepimut-S + Montanide + GM-CSF; Patients will receive 6 injections over 12 weeks. Treatment will be administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) on day -2 if they have been appropriately instructed on SQ injection administration. Patients will be informed of the expected reactions such as irritation at the injection site. Patients will keep a logbook noting the time and placement of the injection. Patients will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide. It will be administered by a nurse (it may not be self administered) subcutaneously to the same anatomical site as the GM-CSF. This site will be marked by the patient or treating healthcare professional by a permanent marker pen.
Placebo Comparator: Montanide + GM-CSF; Montanide adjuvant 1 mL and GM-CSF 70 mcg	Biological: Montanide + GM-CSF; Patients will receive 6 injections over 12 weeks. Treatment will be administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) on day -2 if they have been appropriately instructed on SQ injection administration. Patients will be informed of the expected reactions such as irritation at the injection site. Patients will keep a logbook noting the time and placement of the injection. Patients will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide. It will be administered by a nurse (it may not be self-administered)subcutaneously to the same anatomical site as the GM-CSF. This site will be marked by the patient or treating healthcare professional by a permanent marker pen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year Progression-free Survival	Progression free survival (PFS) rate will be calculated from the time of randomization to first evidence of disease recurrence or death of any cause.	1 year
Progression-free Survival	Median progression free survival (PFS) is where PFS are assessed from the time of randomization to first evidence of disease recurrence or death of any cause.	Up to 5 years and 11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Median overall survival (OS) is estimated from time of randomization to all cause mortality	Uo to 5 years and 11 months
Immune Response	Immunogenicity of galinpepimut-S and control from a subset of participants	12 weeks

Collaborators and Investigators

• Sponsor: Sellas Life Sciences Group
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Marjorie Zauderer, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Zauderer MG, Tsao AS, Dao T, Panageas K, Lai WV, Rimner A, Rusch VW, Adusumilli PS, Ginsberg MS, Gomez D, Rice D, Mehran R, Scheinberg DA, Krug LM. A Randomized Phase II Trial of Adjuvant Galinpepimut-S, WT-1 Analogue Peptide Vaccine, After Multimodality Therapy for Patients with Malignant Pleural Mesothelioma. Clin Cancer Res. 2017 Dec 15;23(24):7483-7489. doi: 10.1158/1078-0432.CCR-17-2169. Epub 2017 Sep 28.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2010
• Primary Completion (Actual): November 30, 2016
• Study Completion (Actual): July 25, 2017

Study Registration Dates

• First Submitted: December 21, 2010
• First Submitted That Met QC Criteria: December 22, 2010
• First Posted (Estimated): December 23, 2010

Study Record Updates

• Last Update Posted (Actual): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Vaccine; GM-CSF; Galinpepimut-S; MONTANIDE ISA 51; WT1 PEPTIDE SPECIFIC T CELLS; 10-134
• 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; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Sargramostim; Monatide (IMS 3015); Molgramostim
• Other Study ID Numbers: 10-134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO