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CompletedNCT02166905Updated Feb 24, 2023Results posted

DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, and IDO1 Inhibitor INCB024360 in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission

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

Phase
Phase 1/2
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma

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03

In context

Carcinoma

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 →

Lead sponsor

Roswell Park Cancer Institute is the lead sponsor of 412 studies on the registry; 62 are open to participants now.

Of its 38 completed or terminated interventional studies of FDA-regulated products, 21 (55%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Eligible patients will be women 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; this may or may not be measurable; these patients would normally enter a period of observation after standard management
  • Any human leukocyte antigen (HLA) type; (historic HLA typing is permitted)
  • Tumor expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) and/or reverse transcriptase polymerase chain reaction (RTPCR)
  • Life expectancy > 6 months
  • Absolute neutrophil count (ANC) >= 1,000/uL
  • Platelets (PLT) >= 100,000/uL
  • Hemoglobin (Hgb) >= 8 g/dL
  • Total bilirubin =\< 1.5 x upper limit of normal (ULN)
  • Serum aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]/AST) or serum alanine aminotransferase (serum glutamate pyruvate transaminase [SGPT]/ALT) =\< 3 x ULN
  • Serum creatinine =\< 2 x ULN
  • Have been informed of other treatment options
  • Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
  • The ability to swallow and retain oral medication
  • Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment
  • Patients may have received previous NY-ESO-1 vaccine therapy; patients who received maintenance paclitaxel or bevacizumab are eligible for enrollment provided they have discontinued therapy (at least 4 weeks for prior taxane or prior bevacizumab) prior to randomization and recovered from toxicities to less than grade 2

Exclusion criteria

Exclusion Criteria:

  • Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available
  • Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders)
  • History of severe autoimmune disorders requiring use of steroids or other immunosuppressives
  • Concomitant systemic treatment with chronic use (based on the investigator's judgment) of corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs, and other platelet inhibitory agents
  • Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing of study drug (6 weeks for nitrosoureas); concomitant hormonal therapies for breast cancers are allowed
  • Subjects being treated with a monoamine oxidase inhibitor (MAOI), or drug which has significant MAOI activity (e.g., Meperidine, linezolid, methylene blue) within 3 weeks prior to screening
  • Subjects who are currently receiving therapy with a potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer or inhibitor (e.g. clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir)
  • Use of UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: diclofenac, imipramine, and ketoconazole
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study drug
  • Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
  • Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study
  • Lack of availability of a patient for immunological and clinical follow-up assessment
  • Evidence of current drug or alcohol abuse or psychiatric impairment, which in the Investigator's opinion will prevent completion of the protocol therapy or follow-up
  • Pregnant or nursing female patients
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug (i.e., any significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the patient's risk by participating in this study)
  • Known hypersensitivity to any of the study drugs that will be given to the participant
  • Additional exclusion criteria for exploratory cohort ONLY: Known pulmonary hypertension
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Arm I (CDX-1401, poly ICLC)

    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

  • Experimental
    Arm II (CDX-1401, poly ICLC, IDO1 inhibitor INCB024360)

    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

Interventions

  • BiologicalDEC-205/NY-ESO-1 Fusion Protein CDX-1401

    Given via intracutaneous injection

    Also known as: CDX-1401

  • DrugEpacadostat

    Given PO

    Also known as: INCB 024360, INCB024360

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • OtherPharmacological Study

    Correlative studies

  • DrugPoly ICLC

    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

06

What researchers measure

Primary outcomes

  1. 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

  2. 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

  3. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

07

Results

Posted Feb 24, 2023

Participant flow

Participant flow — Overall Study
MilestonePhase 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. )
Started716152
Completed616152
Not completed1000
Withdrew: Withdrawal by subject1000

Outcome measures

PrimaryTo 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
Reported as:
Count of participants · Participants
To Determine the Safety and Evaluate Toxicity of Fixed Doses for Phase I Patients
ParticipantsPhase 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 Patients1
PrimaryProgression 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
Reported as:
Number · Proportion of participants w/o Progress
Progression Free Survival (PFS) Based on Immune Related Response Criteria (irRC) for Phase II Patients
Proportion of participants w/o ProgressPhase 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 Patients0.78 (0.52 to 0.91)0.54 (0.29 to 0.73)0.50 (0.02 to 0.88)
Statistical analysis
  • Phase IIb arm1 (CDX-1401, Poly ICLC, IDO1 Without Inhibitor INCB024360) · Log Rank · p = 0.177 · Hazard ratio (hr): 0.4 · 90% CI 0.1 to 1.2Reference=arm 1
PrimaryTo 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
Reported as:
Number · participants
To Evaluate Toxicity as Defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
participantsPhase 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 Events2120
Other Adverse Events614152
SecondaryAntibody 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

No measurements were reported for this outcome.

SecondaryFrequency 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

No measurements were reported for this outcome.

SecondaryNY-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

No measurements were reported for this outcome.

SecondaryT 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

No measurements were reported for this outcome.

Adverse events

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.

Adverse event summary by group
GroupDeathsSeriousOther
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%)
Most frequent serious events
Most frequent serious events
EventPhase 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 disorders1/60/160/150/2
VomitingGastrointestinal disorders1/60/160/150/2
Cardiac deathGeneral disorders0/60/161/150/2
SyncopeNervous system disorders0/60/161/150/2
HypersensitivityImmune system disorders0/61/160/150/2
Most frequent other events
Showing 10 of 79
Most frequent other events
EventPhase 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 disorders1/64/166/152/2
Injection site erythemaGeneral disorders6/66/167/150/2
NauseaGastrointestinal disorders4/63/163/151/2
FatigueGeneral disorders4/63/166/150/2
Injection site painGeneral disorders4/64/164/150/2
ChillsGeneral disorders3/61/162/150/2
Injection site reactionGeneral disorders0/62/164/151/2
SplinterInjury, poisoning and procedural complications0/60/160/151/2
Carbon dioxide increasedInvestigations0/60/160/151/2
White blood cell count decreasedInvestigations0/60/160/151/2

Baseline characteristics

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
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 years00000
Between 18 and 65 years41011126
>=65 years264113
Age, Continuous
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
Mean64 ± 1265 ± 1063 ± 1063 ± 864 ± 10
Sex: Female, Male
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
Female61615239
Male00000
Race (NIH/OMB)
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 Native00000
Asian00101
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White61614238
More than one race00000
Unknown or Not Reported00000
08

Study locations

1 site
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · May 13, 2021

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 24, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02166905
Lead sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI), Celldex Therapeutics, Incyte Corporation
Responsible party
Sponsor
First posted
Jun 18, 2014
Start date
Oct 10, 2014
Primary completion
Aug 20, 2020
Completion
Aug 20, 2020
Results posted
Feb 24, 2023
Last update
Feb 24, 2023

Study contacts

Emese Zsiros, MD
principal investigator · Roswell Park Cancer Institute

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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