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

NCT03006302 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: J16173IRB001185205P01CA247886-02
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Pancreatic Adenocarcinoma

Keywords

Pancreatic cancer; Vaccine; Immunotherapy; Pembrolizumab; PD-1; IDO; CRS-207; Epacadostat

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation

  15 months

Study Arms (5)

Part 1: Dose Level 1

EXPERIMENTAL

Epacadostat/Pembrolizumab/CY/GVAX/CRS-207

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

Part 1: Dose Level 2

EXPERIMENTAL

Epacadostat/Pembrolizumab/CY/GVAX/CRS-207

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

Part 1X: Dose Level 2

EXPERIMENTAL

Epacadostat/Pembrolizumab/CRS-207

Drug: Epacadostat; Drug: Pembrolizumab; Biological: CRS-207

Part 1X: Dose Level 3

EXPERIMENTAL

Epacadostat/Pembrolizumab/CRS-207

Drug: Epacadostat; Drug: Pembrolizumab; Biological: CRS-207

Part 2: Dose Expansion

EXPERIMENTAL

Epacadostat/Pembrolizumab/CRS-207

Drug: Epacadostat; Drug: Pembrolizumab; Biological: CRS-207

Interventions

Epacadostat DRUG

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.

Also known as: INCB024360

Part 1: Dose Level 1; Part 1: Dose Level 2; Part 1X: Dose Level 2; Part 1X: Dose Level 3; Part 2: Dose Expansion

Pembrolizumab DRUG

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.

Also known as: MK-3475, KEYTRUDA

Part 1: Dose Level 1; Part 1: Dose Level 2; Part 1X: Dose Level 2; Part 1X: Dose Level 3; Part 2: Dose Expansion

CRS-207 BIOLOGICAL

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.

Part 1: Dose Level 1; Part 1: Dose Level 2; Part 1X: Dose Level 2; Part 1X: Dose Level 3; Part 2: Dose Expansion

Cyclophosphamide DRUG

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.

Also known as: CY, CYTOXAN

Part 1: Dose Level 1; Part 1: Dose Level 2

GVAX Pancreas Vaccine BIOLOGICAL

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.

Also known as: GVAX, Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo

Part 1: Dose Level 1; Part 1: Dose Level 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator
• Incyte Corporation: collaborator

Study Sites (1)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

epacadostat; pembrolizumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dung Le, MD
• Organization: SKCCC Johns Hopkins Medical Institution

Dle@jhmi.edu

443-287-0002

Study Officials

• Dung Le, M.D.

  The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: December 30, 2016
• Study Start: January 31, 2018
• Primary Completion: August 22, 2023
• Study Completion: August 5, 2024
• Last Updated: October 8, 2024
• Results First Posted: June 20, 2024

Record last verified: 2024-09

Locations

US (1)