Epacadostat, Pembrolizumab, And CRS-207, With Or Without CY/GVAX Pancreas In Patients With Metastatic Pancreas Cancer

Study Overview

Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer

This study will enroll patients who have metastatic pancreatic cancer and have progressed on prior chemotherapy. Part 1 (dose escalation) participants will receive epacadostat/pembrolizumab/cyclophosphamide(CY)/GVAX pancreas vaccine followed by epacadostat/pembrolizumab/CRS-207, Part 1X (dose escalation) participants will receive epacadostat/pembrolizumab/CRS-207. Part 2X (dose expansion) participants will receive epacadostat/pembrolizumab/CRS-207. The primary objectives of this study are to determine the recommended dose of epacadostat in this combination and assess survival of subjects in both treatment groups.

N/A

Metastatic Pancreatic Adenocarcinoma

DRUG: Epacadostat
DRUG: Pembrolizumab
BIOLOGICAL: CRS-207
DRUG: Cyclophosphamide
BIOLOGICAL: GVAX Pancreas Vaccine

J16173
IRB00118520 (OTHER Identifier) (OTHER: JHMIRB)
5P01CA247886-02 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-12-28	Results First Submitted 2024-05-28	Last Update Submitted that met QC Criteria 2024-09-23
First Submitted that Met QC Criteria 2016-12-28	Results First Submitted that Met QC Criteria 2024-05-28	Last Update Posted (ACTUAL) 2024-10-08
First Posted (ACTUAL) 2016-12-30	Results First Posted 2024-06-20	Last Verified 2024-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Part 1: Dose Level 1 Epacadostat/Pembrolizumab/CY/GVAX/CRS-207	DRUG: Epacadostat Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Epacadostat (100, 300, or 600 mg) is taken by mouth twice a day, every day. DRUG: Pembrolizumab Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Pembrolizumab (200 mg) will be administered IV on day 1 of Cycles 1-6. BIOLOGICAL: CRS-207 CRS-207: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 10^9 CFU) will be administered IV on Day 2 of Cycles 3-6. DRUG: Cyclophosphamide Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Cyclophosphamide (200 mg/m^2) will be administered IV on day 1 of Cycles 1 and 2. BIOLOGICAL: GVAX Pancreas Vaccine Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). GVAX will be administered on Day 2 of Cycles 1 and 2.
EXPERIMENTAL: Part 1: Dose Level 2 Epacadostat/Pembrolizumab/CY/GVAX/CRS-207	DRUG: Epacadostat Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Epacadostat (100, 300, or 600 mg) is taken by mouth twice a day, every day. DRUG: Pembrolizumab Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Pembrolizumab (200 mg) will be administered IV on day 1 of Cycles 1-6. BIOLOGICAL: CRS-207 CRS-207: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 10^9 CFU) will be administered IV on Day 2 of Cycles 3-6. DRUG: Cyclophosphamide Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Cyclophosphamide (200 mg/m^2) will be administered IV on day 1 of Cycles 1 and 2. BIOLOGICAL: GVAX Pancreas Vaccine Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). GVAX will be administered on Day 2 of Cycles 1 and 2.
EXPERIMENTAL: Part 1X: Dose Level 2 Epacadostat/Pembrolizumab/CRS-207	DRUG: Epacadostat Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Epacadostat (100, 300, or 600 mg) is taken by mouth twice a day, every day. DRUG: Pembrolizumab Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Pembrolizumab (200 mg) will be administered IV on day 1 of Cycles 1-6. BIOLOGICAL: CRS-207 CRS-207: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 10^9 CFU) will be administered IV on Day 2 of Cycles 3-6.
EXPERIMENTAL: Part 1X: Dose Level 3 Epacadostat/Pembrolizumab/CRS-207	DRUG: Epacadostat Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Epacadostat (100, 300, or 600 mg) is taken by mouth twice a day, every day. DRUG: Pembrolizumab Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Pembrolizumab (200 mg) will be administered IV on day 1 of Cycles 1-6. BIOLOGICAL: CRS-207 CRS-207: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 10^9 CFU) will be administered IV on Day 2 of Cycles 3-6.
EXPERIMENTAL: Part 2: Dose Expansion Epacadostat/Pembrolizumab/CRS-207	DRUG: Epacadostat Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Epacadostat (100, 300, or 600 mg) is taken by mouth twice a day, every day. DRUG: Pembrolizumab Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Pembrolizumab (200 mg) will be administered IV on day 1 of Cycles 1-6. BIOLOGICAL: CRS-207 CRS-207: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 10^9 CFU) will be administered IV on Day 2 of Cycles 3-6.

Primary Outcome Measures	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Epacadostat	Dose escalation (part I of the trial only) to determine the maximum tolerated dose (MTD) in mg BID. Epacadostat (100, 300, or 600 mg) was taken by mouth twice a day, every day.	9 weeks
6 Month Survival	Number of subjects who are alive 6 months or longer after the date of first treatment.	6 months

Secondary Outcome Measures	Measure Description	Time Frame
Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation		15 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Documented adenocarcinoma of the pancreas
Have disease progression after prior chemotherapy for metastatic pancreas cancer (or adjuvant or neoadjuvant if progression occurred within 6 months of completing this regimen)
Presence of at least one measurable lesion
Patient acceptance to have a tumor biopsy of an accessible lesion at 2 time points (baseline and on study)
ECOG performance status of 0 or 1
Life expectancy of greater than 3 months
Adequate organ and marrow function defined by study-specified laboratory tests

Brain metastases
Clinical or radiographic ascites (some trace amount may be allowed)
Rapidly progressing disease
Live vaccine within 30 days of study treatment (flu vaccine allowed)
Surgery within 28 days of study treatment (some exceptions for minor procedures)
Use of an investigational agent or device within 28 days of study treatment.
Chemotherapy, radiation, or biological cancer therapy within 14 days of study treatment.
Prior treatment with anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti PD-L2, or with IDO inhibitor.
Use of growth factors within 14 days of study treatment
Use of any systemic steroids within 14 days of study treatment or other immunosuppressive agents within 7 days of study treatment.
Use of more than 2 g/day of acetaminophen
Use of any UGT1A9 inhibitor
Use of warfarin
Use of MAOIs or drugs with significant MAOI activity within the 21 days of screening
History of Seratonin Syndome
Known allergy to both penicillin and sulfa
Known or suspected hypersensitivity to any monoclonal antibody or any study drug component
Have artificial joints or implants that cannot be easily removed or a history of infection associated with an implant
Significant or malignant pleural effusion
New pulmonary embolism, extremity deep venous thromboembolism, or portal vein thrombosis within 2 months of study enrollment
History of autoimmune disease (exceptions for Graves or Hashimoto's disease, vitiligo, and type I diabetes mellitus)
Gastrointestinal condition that may affect drug absorption
Significant heart disease or heart disease requiring antibiotic for prevention of endocarditis
History of abnormal electrocardiogram (ECG) that is deemed meaningful by the investigator
History of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis
Pulse oximetry of < 92% on room air or the need for supplemental home oxygen
Infection with HIV, hepatitis B or hepatitis C
Other conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access that would affect the patient's ability to comply with study visits and procedures
Pregnant or breastfeeding women
Unwillingness or inability to follow the study schedule for any reason

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Merck Sharp & Dohme LLC
National Cancer Institute (NCI)
Incyte Corporation

Investigators

PRINCIPAL_INVESTIGATOR: Dung Le, M.D., The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications

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General Publications

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