Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer
Study Details
Study Description
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 |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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 Names:
Drug: Pembrolizumab
200 mg IV on Day 1 of each cycle
Other Names:
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:
Biological: GVAX
5x10^8 cells given as 6 intradermal injections on Day 2 of Cycles 1-2 (Arm A only)
Other Names:
|
| 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 Names:
Drug: Pembrolizumab
200 mg IV on Day 1 of each cycle
Other Names:
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
Primary Outcome Measures
- Recommended Dose of Epacadostat [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
- 6 Month Survival [4 years]
Proportion of subjects who are alive 6 months or longer after the date of randomization
Secondary Outcome Measures
- Number of patients experiencing treatment related toxicities [4 years]
- Overall Survival (OS) [4 years]
Average time from randomization to death due to any cause
- Progression Free Survival (PFS) [4 years]
Average time from randomization to disease progression (by RECIST 1.1) or death, whichever comes first
- immune-related Progression Free Survival (irPFS) [4 years]
Average time from randomization to disease progression (by irRC) or death, whichever comes first.
- Objective Response Rate (ORR) [4 years]
Proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) by RECIST 1.1
- immune-related Objective Response Rate (irORR) [4 years]
Proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) by irRC
- Best Overall Response (BOR) [4 years]
Summary of the best response (by RECIST 1.1) achieved by each patient
- immune-related Best Overall Response (irBOR) [4 years]
Summary of the best response (by irRC) achieved by each patient
- Time to Objective Response (TTOR) [4 years]
Average time from randomization to partial or complete response by RECIST 1.1
- immune-related Time to Objective Response (irTTOR) [4 years]
Average time from randomization to partial or complete response by irRC
- Duration of Response (DOR) [4 years]
Average time from partial or complete response to disease progression, by RECIST 1.1
- immune-related Duration of Response (irDOR) [4 years]
Average time from partial or complete response to disease progression, by irRC
- Duration of Clinical Benefit (DCB) [4 years]
Average time from randomization to date of disease progression in subjects achieving a partial or complete response by RECIST 1.1
- immune-related Duration of Clinical Benefit (irDCB) [4 years]
Average time from randomization to date of disease progression in subjects achieving a partial or complete response by RECIST 1.1
- Disease Control Rate (DCR) [4 years]
Percentage of subjects achieving stable disease or better by RECIST 1.1
- immune-related Disease Control Rate (irDCR) [4 years]
Percentage of subjects achieving stable disease or better by irRC
- Tumor Marker (CA19-9) Kinetics [4 years]
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
- Principal Investigator: Dung Le, M.D., The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- J16173
- IRB00118520
- 5P01CA247886-02