Study of IMF-001 in Patients With Malignancies Expressing NY-ESO-1
The purpose of this study is assess the safety of administering repeated doses of IMF-001, a vaccine, to patients with solid tumors that express NY-ESO-1 antigen. If the vaccine is therapeutically useful, a second goal is to establish the maximum therapeutic dose to treat patients with NY-ESO-1 positive cancers.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Therapeutic Cancer Vaccine IMF-001 in Patients With Malignancies Expressing NY-ESO-1|
- Number of patients with adverse events as a measure of safety and tolerability of repeat doses. [ Time Frame: Date of first dose until 30 days after off-study, or until resolution of related AEs ] [ Designated as safety issue: Yes ]
- Tumor response using RECIST 1.1 [ Time Frame: Each cycle at weeks 7 and 11 (appx.) ] [ Designated as safety issue: Yes ]Scans will be performed each cycle after the 4th and 6th injections (approximately Weeks 7 and 11). Scans will be performed; or, for patients with prostate cancer, response will be based on PSA levels.
- Humoral and cellular immune response as indication of IMF-001 biologic activity [ Time Frame: Starting from first dose, samples taken within 72hrs of the 1st, 3rd, and 5th doses of each cycle until off-study ] [ Designated as safety issue: Yes ]Humoral response (NY-ESO-1 antibody titre) Cellular response (NY-ESO-1 specific CD4 and CD8 T-cells)
- Optimal dose based on number of patients with adverse events at that dose [ Time Frame: Date of first dose until 30 days after off-study, or until resolution of related AEs ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment: IMF-001
100 or 200 mcg will be administered to patients subcutaneously every 2 weeks for 6 injections.
subcutaneous injection of fixed dose IMF-001 (100 or 200 mcg) every 2 weeks.
NY-ESO-1 was isolated by serological analysis of recombinant cDNA expression libraries (SEREX), using tumor mRNA and autologous serum from an esophageal cancer patient. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that NY-ESO-1 displayed the typical expression pattern of cancer testis antigens (CT antigens). NY-ESO-1 mRNA was expressed only in testis of normal tissues tested and in various types of cancer, including lung cancer, breast cancer, malignant melanoma and bladder cancer. Since testis is an immune privileged organ where HLA molecules are not expressed, these antigens can be considered tumor-specific.
IMF-001 is a CHP-NY-ESO-1 complex consisting of recombinant NY-ESO-1 protein and cholesteryl hydrophobized pullulan (CHP). CHP forms colloidally stable nanoparticles in water and complexes with substrate such as NY-ESO-1 protein.
It is well known that exogenous antigen proteins can induce specific CD4+ T cells but not specific CD8+ T cell. Dendritic cells pulsed with IMF-001 induced NY-ESO-1 specific CD8+ T cells in blood samples of 4 healthy volunteers. These data suggest that immunization of patients with IMF-001 can evoke not only specific CD4+ T cells responses but also specific CD8+ T cell response to NY-ESO-1 more effectively than NY-ESO-1 protein alone. Similar results for both cellular and humoral immunity in response to NY-ESO-1 protein were observed in previous clinical investigational studies with IMF-001.
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|New York University (NYU) Cancer Center|
|New York, New York, United States, 10016|
|Study Director:||DAIJU ICHIMARU, BS||ImmunoFrontier, Inc.|