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

Johns Hopkins Medicine

Status and phase: Completed; Phase 2

Conditions: Metastatic Pancreatic Adenocarcinoma

Treatments: Drug: Cyclophosphamide; Drug: Pembrolizumab; Biological: GVAX Pancreas Vaccine; Drug: Epacadostat; Biological: CRS-207

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT03006302

IRB00118520 (Other Identifier)

5P01CA247886-02 (Other Identifier)

J16173

Details and patient eligibility

About

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.

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

41 participants in 5 patient groups

Part 1: Dose Level 1

Experimental group

Description:

Epacadostat/Pembrolizumab/CY/GVAX/CRS-207

Treatment:

Biological: CRS-207

Drug: Epacadostat

Biological: GVAX Pancreas Vaccine

Drug: Pembrolizumab

Drug: Cyclophosphamide

Part 1: Dose Level 2

Experimental group

Description:

Epacadostat/Pembrolizumab/CY/GVAX/CRS-207

Treatment:

Biological: CRS-207

Drug: Epacadostat

Biological: GVAX Pancreas Vaccine

Drug: Pembrolizumab

Drug: Cyclophosphamide

Part 1X: Dose Level 2

Experimental group

Description:

Epacadostat/Pembrolizumab/CRS-207

Treatment:

Biological: CRS-207

Drug: Epacadostat

Drug: Pembrolizumab

Part 1X: Dose Level 3

Experimental group

Description:

Epacadostat/Pembrolizumab/CRS-207

Treatment:

Biological: CRS-207

Drug: Epacadostat

Drug: Pembrolizumab

Part 2: Dose Expansion

Experimental group

Description:

Epacadostat/Pembrolizumab/CRS-207

Treatment:

Biological: CRS-207

Drug: Epacadostat

Drug: Pembrolizumab