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

Study Overview
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Brief Summary
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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.

Official Title
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Phase 2 Study of Epacadostat, Pembrolizumab, and CRS-207, With or Without Cyclophosphamide and GVAX Pancreas Vaccine in Patients With Metastatic Pancreas Cancer

Conditions
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Metastatic Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: Epacadostat
* Drug: Pembrolizumab
* Biological: CRS-207
* Drug: CY
* Biological: GVAX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (abbreviated): 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 Exclusion Criteria (abbreviated): 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epacadostat/Pembrolizumab/CY/GVAX/CRS-207<br> | Drug: Epacadostat<br>* 50, 100, 300, or 600 mg taken by mouth twice a day, every day of each cycle<br>* Other names: INCB024360;Drug: Pembrolizumab<br>* 200 mg IV on Day 1 of each cycle<br>* Other names: anti-PD-1 mAb;Biological: CRS-207<br>* 1x10^9 CFU given IV on Day 2 of Cycles 3-6 (Arm A) or Day 2 of Cycles 1-6 (Arm B)<br>Drug: CY<br>* 200 mg/m^2 given IV on Day 1 of Cycles 1-2 (Arm A only)<br>* Other names: cytoxan;Biological: GVAX<br>* 5x10^8 cells given as 6 intradermal injections on Day 2 of Cycles 1-2 (Arm A only)<br>* Other names: Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo;|
| Experimental: Epacadostat/Pembrolizumab/CRS-207<br> | Drug: Epacadostat<br>* 50, 100, 300, or 600 mg taken by mouth twice a day, every day of each cycle<br>* Other names: INCB024360;Drug: Pembrolizumab<br>* 200 mg IV on Day 1 of each cycle<br>* Other names: anti-PD-1 mAb;Biological: CRS-207<br>* 1x10^9 CFU given IV on Day 2 of Cycles 3-6 (Arm A) or Day 2 of Cycles 1-6 (Arm B)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended Dose of Epacadostat | Evaluate 4 dose levels of epacadostat, in order to determine recommended dose for use in combination with pembrolizumab, CY, GVAX, and CRS-207 | 1 year | 
| 6 Month Survival | Proportion of subjects who are alive 6 months or longer after the date of randomization | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing drug-related adverse events (AEs) requiring treatment discontinuation |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, pancreatic cancer, vaccine, MK-3475, PD-1, IDO