This partially randomized phase I/IIb trial studies the side effects and best dose of IDO1 inhibitor INCB024360 in combination with DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC and to see how well they work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer who no longer have evidence of disease. Antigens (such as cancer/testis antigen \[NY-ESO-1\] protein) are found on many cancer cells. Vaccines made from NY-ESO-1 protein may cause the immune system to produce immune cells and antibodies that may help locate the NY-ESO-1 and/or cancer/testis antigen 2 (LAGE-1) antigens on cancer cells. By finding them, the immune system may then work to control or eliminate the remaining cancer cells. INCB024360 is an inhibitor of an enzyme called indoleamine 2,3 dioxygenase (IDO). This enzyme is produced by tumor cells to disable immune cells, and limit the efficacy of immune attack. Giving DEC-205/NY-ESO-1 fusion protein CDX-1401 with poly ICLC and IDO1 inhibitor INCB024360 may generate stronger and more long lasting anti-cancer immune responses in patients with ovarian, fallopian tube, and primary peritoneal cancer in remission.
PRIMARY OBJECTIVES: I. To determine the safety of fixed doses of DEC205mAb-NY-ESO-1 fusion protein (DEC-205/NY-ESO-1 fusion protein CDX-1401) with adjuvant poly-ICLC given as a vaccine in combination with INCB024360 (IDO1 inhibitor INCB024360). (Phase I) II. To evaluate toxicity as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. (Phase I) III. To determine the progression free survival (PFS) (primary endpoint) using standard immune-related response criteria (irRC) criteria. (Phase IIb) SECONDARY OBJECTIVES: I. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing cancer-testis antigen (NY-ESO-1) specific cellular and humoral immunity. II. To determine the effectiveness of Sirolimus on enhancing vaccine efficacy by assessing NY-ESO-1 specific cellular and humoral immunity (Exploratory Cohort ONLY) III. Peripheral blood NY-ESO-1 specific cluster of differentiation (CD)8+ and CD4+ T cells. (Exploratory Cohort ONLY) IV. Peripheral blood NY-ESO-1 specific antibodies.(Exploratory Cohort ONLY) V. Peripheral blood frequency of CD4+CD25+forkhead box P3 (FOXP3)+ regulatory T cells. (Exploratory Cohort ONLY) VI. Pharmacokinetics of INCB02360 in relation to T cell frequency and function in correlation with PFS. (Exploratory Cohort ONLY) OUTLINE: PHASE I: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 via intracutaneous injection on day 1, poly ICLC subcutaneously (SC) on days 1 and 2, and IDO1 inhibitor INCB024360 orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients receive IDO1 inhibitor INCB024360 for up to 7 courses. PHASE IIb: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC as in Phase I. ARM II: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, and IDO1 inhibitor INCB024360 as in Phase I. After completion of study treatment, patients are followed up for 30 days and then at 3, 6, and 12 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Given via intracutaneous injection
Given PO
Correlative studies
Correlative studies
Given SC
Roswell Park Cancer Institute
Buffalo, New York, United States
To Determine the Safety and Evaluate Toxicity of Fixed Doses for Phase I Patients
To determine the safety of fixed doses of DEC205mAb-NY-ESO-1 fusion protein with adjuvant poly-ICLC given as a vaccine in combination with INCB024360 300mg, number of Participants with Dose Limiting Toxicities is reported
Time frame: 28 days
Progression Free Survival (PFS) Based on Immune Related Response Criteria (irRC) for Phase II Patients
Percentage of Participants with Progression Free Survival Using irRC Criteria for Phase II Patients are reported. irRC criteria disease progression is defined as at least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 weeks apart.
Time frame: Up to 6 months
To Evaluate Toxicity as Defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
All patients enrolled in this study will be eligible for the analysis of toxicity. The toxicity rate will be estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson).
Time frame: Up to 12 months
Antibody Titers
Due to the PI leaving the institute, these biomarker data were not generated and are therefore not available to be analyzed.
Time frame: Up to 12 months
Frequency of Memory T Cell Populations
Due to the PI leaving the institute, these biomarker data were not generated and are therefore not available to be analyzed.
Time frame: Up to 12 months
NY-ESO-1 Specific CD8+ and CD4+ Frequency and Function
Due to the PI leaving the institute, these biomarker data were not generated and are therefore not available to be analyzed.
Time frame: Up to 12 months
T Cell Receptor (TCR) Avidity
Due to the PI leaving the institute, these biomarker data were not generated and are therefore not available to be analyzed.
Time frame: Up to 12 months
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