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

Phase 2 Study of Epacadostat, Pembrolizumab, and CRS-207, With or Without Cyclophosphamide and GVAX Pancreas Vaccine 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.

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Epacadostat; Drug: Pembrolizumab; Biological: CRS-207; Drug: Cyclophosphamide; Biological: GVAX Pancreas Vaccine

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

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.; Other Names: INCB024360; 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.; Other Names: KEYTRUDA; MK-3475; 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.; Other Names: CY; CYTOXAN; 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.; Other Names: Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo; GVAX
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.; Other Names: INCB024360; 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.; Other Names: KEYTRUDA; MK-3475; 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.; Other Names: CY; CYTOXAN; 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.; Other Names: Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo; GVAX
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.; Other Names: INCB024360; 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.; Other Names: KEYTRUDA; MK-3475; 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.; Other Names: INCB024360; 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.; Other Names: KEYTRUDA; MK-3475; 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.; Other Names: INCB024360; 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.; Other Names: KEYTRUDA; MK-3475; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI); Merck Sharp & Dohme LLC; Incyte Corporation
• Investigators: Principal Investigator: Dung Le, M.D., The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2018
• Primary Completion (Actual): August 22, 2023
• Study Completion (Actual): August 5, 2024

Study Registration Dates

• First Submitted: December 28, 2016
• First Submitted That Met QC Criteria: December 28, 2016
• First Posted (Estimated): December 30, 2016

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Vaccine; Immunotherapy; Pembrolizumab; PD-1; Pancreatic cancer; Epacadostat; IDO; CRS-207
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Cyclophosphamide; Pembrolizumab; Pancrelipase
• Other Study ID Numbers: J16173; IRB00118520 (Other Identifier: JHMIRB); 5P01CA247886-02 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No