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
Brief 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.
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximum tolerated dose determined by the incidence of dose limiting toxicities graded according to NCI CTCAE version 4.0 (Phase I)
Secondary Outcome
Antibody titers
Condition
Fallopian Tube Carcinoma
Intervention
DEC-205/NY-ESO-1 Fusion Protein CDX-1401
Study Arms / Comparison Groups
Arm I (CDX-1401, poly ICLC)
Description: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC as in Phase I.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
40
Start Date
August 1, 2014
Completion Date
March 27, 2022
Primary Completion Date
March 27, 2021
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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Kunle Odunsi, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02166905
Organization ID
I 248613
Secondary IDs
NCI-2014-00771
Responsible Party
Sponsor
Study Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Kunle Odunsi, Principal Investigator, Roswell Park Cancer Institute
Verification Date
December 2020