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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03006302
Recruitment Status : Active, not recruiting
First Posted : December 30, 2016
Last Update Posted : January 5, 2023
Sponsor:
Collaborators:
Merck Sharp & Dohme LLC
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Drug: Epacadostat Drug: Pembrolizumab Biological: CRS-207 Drug: CY Biological: GVAX Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study of Epacadostat, Pembrolizumab, and CRS-207, With or Without Cyclophosphamide and GVAX Pancreas Vaccine in Patients With Metastatic Pancreas Cancer
Actual Study Start Date : January 31, 2018
Estimated Primary Completion Date : December 1, 2023
Estimated Study Completion Date : December 1, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Epacadostat/Pembrolizumab/CY/GVAX/CRS-207 Drug: Epacadostat
50, 100, 300, or 600 mg taken by mouth twice a day, every day of each cycle
Other Name: INCB024360

Drug: Pembrolizumab
200 mg IV on Day 1 of each cycle
Other Names:
  • MK-3475
  • anti-PD-1 mAb

Biological: CRS-207
1x10^9 CFU given IV on Day 2 of Cycles 3-6 (Arm A) or Day 2 of Cycles 1-6 (Arm B)

Drug: CY
200 mg/m^2 given IV on Day 1 of Cycles 1-2 (Arm A only)
Other Names:
  • cyclophosphamide
  • cytoxan

Biological: GVAX
5x10^8 cells given as 6 intradermal injections on Day 2 of Cycles 1-2 (Arm A only)
Other Names:
  • GVAX Pancreas Vaccine
  • Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo
Experimental: Epacadostat/Pembrolizumab/CRS-207 Drug: Epacadostat
50, 100, 300, or 600 mg taken by mouth twice a day, every day of each cycle
Other Name: INCB024360

Drug: Pembrolizumab
200 mg IV on Day 1 of each cycle
Other Names:
  • MK-3475
  • anti-PD-1 mAb

Biological: CRS-207
1x10^9 CFU given IV on Day 2 of Cycles 3-6 (Arm A) or Day 2 of Cycles 1-6 (Arm B)


Outcome Measures
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Primary Outcome Measures :
  1. Recommended Dose of Epacadostat [ Time Frame: 1 year ]
    Evaluate 4 dose levels of epacadostat, in order to determine recommended dose for use in combination with pembrolizumab, CY, GVAX, and CRS-207

  2. 6 Month Survival [ Time Frame: 4 years ]
    Proportion of subjects who are alive 6 months or longer after the date of randomization


Secondary Outcome Measures :
  1. Number of patients experiencing treatment related toxicities [ Time Frame: 4 years ]
  2. Overall Survival (OS) [ Time Frame: 4 years ]
    Average time from randomization to death due to any cause

  3. Progression Free Survival (PFS) [ Time Frame: 4 years ]
    Average time from randomization to disease progression (by RECIST 1.1) or death, whichever comes first

  4. immune-related Progression Free Survival (irPFS) [ Time Frame: 4 years ]
    Average time from randomization to disease progression (by irRC) or death, whichever comes first.

  5. Objective Response Rate (ORR) [ Time Frame: 4 years ]
    Proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) by RECIST 1.1

  6. immune-related Objective Response Rate (irORR) [ Time Frame: 4 years ]
    Proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) by irRC

  7. Best Overall Response (BOR) [ Time Frame: 4 years ]
    Summary of the best response (by RECIST 1.1) achieved by each patient

  8. immune-related Best Overall Response (irBOR) [ Time Frame: 4 years ]
    Summary of the best response (by irRC) achieved by each patient

  9. Time to Objective Response (TTOR) [ Time Frame: 4 years ]
    Average time from randomization to partial or complete response by RECIST 1.1

  10. immune-related Time to Objective Response (irTTOR) [ Time Frame: 4 years ]
    Average time from randomization to partial or complete response by irRC

  11. Duration of Response (DOR) [ Time Frame: 4 years ]
    Average time from partial or complete response to disease progression, by RECIST 1.1

  12. immune-related Duration of Response (irDOR) [ Time Frame: 4 years ]
    Average time from partial or complete response to disease progression, by irRC

  13. Duration of Clinical Benefit (DCB) [ Time Frame: 4 years ]
    Average time from randomization to date of disease progression in subjects achieving a partial or complete response by RECIST 1.1

  14. immune-related Duration of Clinical Benefit (irDCB) [ Time Frame: 4 years ]
    Average time from randomization to date of disease progression in subjects achieving a partial or complete response by RECIST 1.1

  15. Disease Control Rate (DCR) [ Time Frame: 4 years ]
    Percentage of subjects achieving stable disease or better by RECIST 1.1

  16. immune-related Disease Control Rate (irDCR) [ Time Frame: 4 years ]
    Percentage of subjects achieving stable disease or better by irRC

  17. Tumor Marker (CA19-9) Kinetics [ Time Frame: 4 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03006302


Locations
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United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Merck Sharp & Dohme LLC
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Dung Le, M.D. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
More Information
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03006302    
Other Study ID Numbers: J16173
IRB00118520 ( Other Identifier: JHMIRB )
5P01CA247886-02 ( U.S. NIH Grant/Contract )
First Posted: December 30, 2016    Key Record Dates
Last Update Posted: January 5, 2023
Last Verified: January 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
pancreatic cancer
vaccine
immunotherapy
 MK-3475
PD-1
IDO
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Cyclophosphamide
Pembrolizumab
 Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological