A Phase 1/2 interventional study of DEC-205/NY-ESO-1 Fusion Protein CDX-1401 and Epacadostat in Fallopian Tube Carcinoma, Ovarian Carcinoma and Primary Peritoneal Carcinoma, sponsored by Roswell Park Cancer Institute. Completed at 1 site in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-24.
Sponsored by Roswell Park Cancer Institute · Phase 1/2, Interventional, and Treatment
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.
6,741 studies on the registry are indexed under Carcinoma; 1,163 are open to participants now.
This study's enrollment of 40 is below the median of 45 across 5,174 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →Roswell Park Cancer Institute is the lead sponsor of 412 studies on the registry; 62 are open to participants now.
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Exclusion Criteria:
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC as in Phase I.
Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401 · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study · Drug: Poly ICLC
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, and IDO1 inhibitor INCB024360 as in Phase I.
Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401 · Drug: Epacadostat · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study · Drug: Poly ICLC
Given via intracutaneous injection
Also known as: CDX-1401
Given PO
Also known as: INCB 024360, INCB024360
Correlative studies
Correlative studies
Given SC
Also known as: Hiltonol, Poly I:Poly C with Poly-L-Lysine Stabilizer, poly-ICLC, PolyI:PolyC with Poly-L-Lysine Stabilizer, Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose, Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose, Stabilized Polyriboinosinic/Polyribocytidylic Acid
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
| Milestone | Phase I (CDX-1401, Poly ICLC) | Phase IIb arm1 (CDX-1401, Poly ICLC, IDO1 Without Inhibitor INCB024360) | Phase IIb arm2 (CDX-1401, Poly ICLC, With IDO1 Inhibitor INCB024360) | Phase IIb Arm 3 (Exploratory Cohort. Enrollment at Roswell Park Site ONLY. ) |
|---|---|---|---|---|
| Started | 7 | 16 | 15 | 2 |
| Completed | 6 | 16 | 15 | 2 |
| Not completed | 1 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 | 0 |
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
| Participants | Phase I (CDX-1401, Poly ICLC, and a Fixed Daily Dose of INCB024360 ) |
|---|---|
| To Determine the Safety and Evaluate Toxicity of Fixed Doses for Phase I Patients | 1 |
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.
| Proportion of participants w/o Progress | Phase IIb arm1 (CDX-1401, Poly ICLC, IDO1 Without Inhibitor INCB024360) | Phase IIb arm2 (CDX-1401, Poly ICLC, With IDO1 Inhibitor INCB024360) | Phase IIb Arm 3 (Exploratory Cohort. Enrollment at Roswell Park Site ONLY. ) |
|---|---|---|---|
| Progression Free Survival (PFS) Based on Immune Related Response Criteria (irRC) for Phase II Patients | 0.78 (0.52 to 0.91) | 0.54 (0.29 to 0.73) | 0.50 (0.02 to 0.88) |
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).
| participants | Phase I (CDX-1401, Poly ICLC, and a Fixed Daily Dose of INCB024360 ) | Arm II 2a (CDX-1401, Poly ICLC, Without IDO1 Inhibitor INCB024360) | Arm II 2b (CDX-1401, Poly ICLC, With IDO1 Inhibitor INCB024360) | Phase IIb Arm 3 (Exploratory Cohort ) |
|---|---|---|---|---|
| Serious Adverse Events | 2 | 1 | 2 | 0 |
| Other Adverse Events | 6 | 14 | 15 | 2 |
Due to the PI leaving the institute, these biomarker data were not generated and are therefore not available to be analyzed.
No measurements were reported for this outcome.
Due to the PI leaving the institute, these biomarker data were not generated and are therefore not available to be analyzed.
No measurements were reported for this outcome.
Due to the PI leaving the institute, these biomarker data were not generated and are therefore not available to be analyzed.
No measurements were reported for this outcome.
Due to the PI leaving the institute, these biomarker data were not generated and are therefore not available to be analyzed.
No measurements were reported for this outcome.
Collected over Between the start date of intervention until 30 days after the last intervention or until the study participant is lost to follow up, the start of new treatment, or until the study investigator assesses the event(s) as stable or irreversible, up to 1 year.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase I (CDX-1401, Poly ICLC, and a Fixed Daily Dose of INCB024360 ) | 0/6 (0%) | 2/6 (33.3%) | 6/6 (100%) |
| Phase II 2a (CDX-1401, Poly ICLC) | 0/16 (0%) | 1/16 (6.3%) | 14/16 (87.5%) |
| Phase II 2b (CDX-1401, Poly ICLC With INCB024360) | 3/15 (20%) | 2/15 (13.3%) | 15/15 (100%) |
| Phase II 3 (Exploratory Cohort) | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Event | Phase I (CDX-1401, Poly ICLC, and a Fixed Daily Dose of INCB024360 ) | Phase II 2a (CDX-1401, Poly ICLC) | Phase II 2b (CDX-1401, Poly ICLC With INCB024360) | Phase II 3 (Exploratory Cohort) |
|---|---|---|---|---|
| Abdominal painGastrointestinal disorders | 1/6 | 0/16 | 0/15 | 0/2 |
| VomitingGastrointestinal disorders | 1/6 | 0/16 | 0/15 | 0/2 |
| Cardiac deathGeneral disorders | 0/6 | 0/16 | 1/15 | 0/2 |
| SyncopeNervous system disorders | 0/6 | 0/16 | 1/15 | 0/2 |
| HypersensitivityImmune system disorders | 0/6 | 1/16 | 0/15 | 0/2 |
| Event | Phase I (CDX-1401, Poly ICLC, and a Fixed Daily Dose of INCB024360 ) | Phase II 2a (CDX-1401, Poly ICLC) | Phase II 2b (CDX-1401, Poly ICLC With INCB024360) | Phase II 3 (Exploratory Cohort) |
|---|---|---|---|---|
| Influenza like illnessGeneral disorders | 1/6 | 4/16 | 6/15 | 2/2 |
| Injection site erythemaGeneral disorders | 6/6 | 6/16 | 7/15 | 0/2 |
| NauseaGastrointestinal disorders | 4/6 | 3/16 | 3/15 | 1/2 |
| FatigueGeneral disorders | 4/6 | 3/16 | 6/15 | 0/2 |
| Injection site painGeneral disorders | 4/6 | 4/16 | 4/15 | 0/2 |
| ChillsGeneral disorders | 3/6 | 1/16 | 2/15 | 0/2 |
| Injection site reactionGeneral disorders | 0/6 | 2/16 | 4/15 | 1/2 |
| SplinterInjury, poisoning and procedural complications | 0/6 | 0/16 | 0/15 | 1/2 |
| Carbon dioxide increasedInvestigations | 0/6 | 0/16 | 0/15 | 1/2 |
| White blood cell count decreasedInvestigations | 0/6 | 0/16 | 0/15 | 1/2 |
Eligible patients will be women ≥ 18 years, with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma after chemotherapy with no evidence of disease or minimal residual disease for primary or recurrent disease.
| Age, Categorical(Participants) | Phase I (CDX-1401, Poly ICLC) | Phase IIb arm1 (CDX-1401, Poly ICLC, IDO1 Without Inhibitor INCB024360) | Phase IIb arm2 (CDX-1401, Poly ICLC, With IDO1 Inhibitor INCB024360) | Phase IIb Arm 3 (Exploratory Cohort. Enrollment at Roswell Park Site ONLY. ) | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 4 | 10 | 11 | 1 | 26 |
| >=65 years | 2 | 6 | 4 | 1 | 13 |
| Age, Continuous(years) | Phase I (CDX-1401, Poly ICLC) | Phase IIb arm1 (CDX-1401, Poly ICLC, IDO1 Without Inhibitor INCB024360) | Phase IIb arm2 (CDX-1401, Poly ICLC, With IDO1 Inhibitor INCB024360) | Phase IIb Arm 3 (Exploratory Cohort. Enrollment at Roswell Park Site ONLY. ) | Total |
|---|---|---|---|---|---|
| Mean | 64 ± 12 | 65 ± 10 | 63 ± 10 | 63 ± 8 | 64 ± 10 |
| Sex: Female, Male(Participants) | Phase I (CDX-1401, Poly ICLC) | Phase IIb arm1 (CDX-1401, Poly ICLC, IDO1 Without Inhibitor INCB024360) | Phase IIb arm2 (CDX-1401, Poly ICLC, With IDO1 Inhibitor INCB024360) | Phase IIb Arm 3 (Exploratory Cohort. Enrollment at Roswell Park Site ONLY. ) | Total |
|---|---|---|---|---|---|
| Female | 6 | 16 | 15 | 2 | 39 |
| Male | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Phase I (CDX-1401, Poly ICLC) | Phase IIb arm1 (CDX-1401, Poly ICLC, IDO1 Without Inhibitor INCB024360) | Phase IIb arm2 (CDX-1401, Poly ICLC, With IDO1 Inhibitor INCB024360) | Phase IIb Arm 3 (Exploratory Cohort. Enrollment at Roswell Park Site ONLY. ) | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 |
| White | 6 | 16 | 14 | 2 | 38 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
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