Clinical Trials /

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

NCT02166905

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: A Phase I/IIb Study of DEC205mAb-NY-ESO-1 Fusion Protein (CDX-1401) Given With Adjuvant Poly-ICLC in Combination With INCB024360 for Patients in Remission With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen

Clinical Trial IDs

  • ORG STUDY ID: I 248613
  • SECONDARY ID: NCI-2014-00771
  • SECONDARY ID: I 248613
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT02166905

Conditions

  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
DEC-205/NY-ESO-1 Fusion Protein CDX-1401CDX-1401Arm I (CDX-1401, poly ICLC)
EpacadostatINCB 024360, INCB024360Arm II (CDX-1401, poly ICLC, IDO1 inhibitor INCB024360)
Poly ICLCHiltonol, 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 AcidArm I (CDX-1401, poly ICLC)

Purpose

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.

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.

      IV. Peripheral blood NY-ESO-1 specific antibodies. V. Peripheral blood frequency of
      CD4+CD25+forkhead box P3 (FOXP3)+ regulatory T cells.

      VI. Pharmacokinetics of INCB02360 in relation to T cell frequency and function in correlation
      with PFS.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (CDX-1401, poly ICLC)ExperimentalPatients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC as in Phase I.
  • DEC-205/NY-ESO-1 Fusion Protein CDX-1401
  • Poly ICLC
Arm II (CDX-1401, poly ICLC, IDO1 inhibitor INCB024360)ExperimentalPatients receive DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, and IDO1 inhibitor INCB024360 as in Phase I.
  • DEC-205/NY-ESO-1 Fusion Protein CDX-1401
  • Epacadostat
  • Poly ICLC

Eligibility Criteria

        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:

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose determined by the incidence of dose limiting toxicities graded according to NCI CTCAE version 4.0 (Phase I)
Time Frame:28 days
Safety Issue:
Description:Analyzed using a Cox proportional hazards model.

Secondary Outcome Measures

Measure:Antibody titers
Time Frame:Up to 12 months
Safety Issue:
Description:Antibody titers will be analyzed via an analysis-of-covariance (ANCOVA) model with post-treatment levels modeled as a function pre-treatment levels and main effects to the parallel design.
Measure:Frequency of memory T cell populations
Time Frame:Up to 12 months
Safety Issue:
Description:The frequency of memory T cell population will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pre-treatment levels and main effects to the parallel design.
Measure:Incidence of toxicity assessed according to NCI CTCAE version 4.0
Time Frame:Up to 12 months
Safety Issue:
Description:The toxicity rate will be estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson). The lower one sided limit will be used.
Measure:NY-ESO-1 specific CD8+ and CD4+ frequency and function
Time Frame:Up to 12 months
Safety Issue:
Description:NY-ESO-1 specific CD8+ and CD4+ frequency and function will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pre-treatment levels and main effects to the parallel design.
Measure:T cell receptor (TCR) avidity
Time Frame:Up to 12 months
Safety Issue:
Description:TCR avidity will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pre-treatment levels and main effects to the parallel design.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

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