INCB024360 and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma
This pilot phase II trial studies how well INCB024360 (indoleamine 2,3-dioxygenase 1 [IDO1] inhibitor INCB024360) and vaccine therapy work in treating patients with stage III-IV melanoma. IDO1 inhibitor INCB024360 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vaccines made from peptides and antigens may help the body build an effective immune response to kill tumor cells. Giving IDO1 inhibitor INCB024360 with vaccine therapy may be an effective treatment for advanced melanoma.
Recurrent Uveal Melanoma
Stage IIIA Skin Melanoma
Stage IIIA Uveal Melanoma
Stage IIIB Skin Melanoma
Stage IIIB Uveal Melanoma
Stage IIIC Skin Melanoma
Stage IIIC Uveal Melanoma
Stage IV Skin Melanoma
Stage IV Uveal Melanoma
Drug: IDO1 Inhibitor INCB024360
Biological: MELITAC 12.1 Peptide Vaccine
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Pilot Trial of an Indoleamine 2,3, Dioxygenase-1 (IDO1) Inhibitor (INCB024360) Plus a Multipeptide Melanoma Vaccine (MELITAC 12.1) in Patients With Advanced Melanoma|
- Changes in the concentration and number of CD8+ cells infiltrating tumor by IHC [ Time Frame: Baseline to up to 16 weeks ] [ Designated as safety issue: No ]
- Changes in the level or character of the vaccine-induced CD8+ and CD4+ specific T-cell immune responses by IFN-gamma ELISPOT [ Time Frame: Baseline to up to 16 weeks ] [ Designated as safety issue: No ]Assessment of immunologic response will be based on a fold-increase measure from baseline as well as using a positivity threshold.
- Change in the number and character of PBMC populations, including T and NK cells, as evaluated by multiparameter flow cytometry [ Time Frame: Baseline to up to 1 year ] [ Designated as safety issue: No ]
- Change in PBMC transcriptome [ Time Frame: Baseline to up to 16 weeks ] [ Designated as safety issue: No ]Analysis of PBMC gene signature. This may be compared to immunologic response, tumor biopsy data and clinical response.
- Incidence of adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
- Overall response rate using the Response Evaluation Criteria In Solid Tumors (RECIST) or Immune-Related Response Criteria (irRC) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
- Time to tumor progression using RECIST or irRC [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: From the time measurement criteria are met for complete response or partial response until the first date that recurrent and progressive disease is objectively documented, assessed up to 1 year ] [ Designated as safety issue: No ]
- Changes in expression of IDO1 protein by IHC in tumor or tumor-infiltrating cells [ Time Frame: Baseline up to 16 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||September 2013|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (INCB024360, MELITAC 12.1)
Patients receive IDO1 inhibitor INCB024360 PO BID on days 1-98 and receive MELITAC 12.1 peptide vaccine ID/SC on days 21, 28, 35, 56, 77, and 98 for up to 3 additional courses in the absence of disease progression or unacceptable toxicity.
Drug: IDO1 Inhibitor INCB024360
Other Names:Biological: MELITAC 12.1 Peptide Vaccine
Other Name: MELITAC 12.1Other: Laboratory Biomarker Analysis
I. To determine the extent to which a regimen of INCB024360 that normalizes serum kynurenine (Kyn)/ tryptophan (Trp) ratios alters the tumor microenvironment of melanoma, including determining the number and character of tumor-infiltrating lymphocytes as determined by examination of serial biopsies with immunohistochemistry (IHC) and gene signatures.
II. To determine the extent to which continued INCB024360 treatment plus the addition of the multipeptide melanoma vaccine, MELITAC 12.1 (MELITAC 12.1 peptide vaccine), further alters the tumor microenvironment of melanoma, including determining the number and character of tumor-infiltrating lymphocytes as determined by serial biopsies evaluating IHC and gene signatures.
I. To determine whether a regimen of INCB024360 that normalizes serum Kyn/Trp ratios plus MELITAC 12.1 vaccine changes the level or character of the vaccine-induced clusters of differentiation (CD) 8+ and CD4+ T-cell immune responses as measured in peripheral blood, as compared to prior published experience.
II. To evaluate the extent to which INCB024360 plus MELITAC 12.1 vaccine alters the number and character of peripheral blood mononuclear cell (PBMC) populations, including T and natural killer (NK) cells, as evaluated by multiparameter flow cytometry.
III. To evaluate the extent to which INCB024360 plus MELITAC 12.1 vaccine alters the PBMC transcriptome.
IV. To assess the safety and tolerability of INCB024360 plus MELITAC 12.1 vaccine.
V. To obtain preliminary data on the tumor response rate of INCB024360 plus MELITAC 12.1 vaccine by objective response rate (ORR), time to tumor progression, and overall survival.
VI. To associate any observed changes with the expression of IDO1 protein by IHC in tumor or tumor-infiltrating cells.
Patients receive IDO1 inhibitor INCB024360 orally (PO) twice daily (BID) on days 1-98 and receive MELITAC 12.1 peptide vaccine intradermally (ID)/subcutaneously (SC) on days 21, 28, 35, 56, 77, and 98. Treatment with IDO1 inhibitor INCB024360 may repeat every 98 days for up to 3 additional courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01961115
|United States, Georgia|
|Emory University/Winship Cancer Institute||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Keith A. Delman 404-778-3303|
|Principal Investigator: Keith A. Delman|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Douglas S Tyler 919-684-6858|
|Principal Investigator: Douglas S Tyler|
|United States, Ohio|
|Cleveland Clinic Foundation||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Marc S. Ernstoff 216-444-0888|
|Principal Investigator: Marc S. Ernstoff|
|United States, Virginia|
|University of Virginia||Recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Craig L. Slingluff 434-924-1730|
|Principal Investigator: Craig L. Slingluff|
|Principal Investigator:||Craig Slingluff||Cancer Immunotherapy Trials Network|