Pilot Study With CY, Pembrolizumab, GVAX, and IMC-CS4 (LY3022855) in Patients With Borderline Resectable Adenocarcinoma of the Pancreas

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03153410

Collaborator

Merck Sharp & Dohme LLC (Industry), Eli Lilly and Company (Industry)

Enrollment

Location

Arm

50.1

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will be looking at whether combining cyclophosphamide, pembrolizumab (an antibody that blocks negative signals to T cells), GVAX (pancreatic cancer vaccine), and IMC-CS4 (LY3022855) (an antibody that blocks a molecule called CSF1-R which prevents the bodies ability to fight cancer) is effective (anti-tumor activity) and safe in patients with borderline resectable pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: Cyclophosphamide Drug: GVAX Drug: Pembrolizumab Drug: IMC-CS4	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study of a GVAX Pancreas Vaccine (With Cyclophosphamide) in Combination With a PD-1 Blockade Antibody (Pembrolizumab) and a Macrophage Targeting Agent (CSF1R Inhibitor) for the Treatment of Patients With Borderline Resectable Adenocarcinoma of the Pancreas

Actual Study Start Date :

Sep 27, 2018

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4	Drug: Cyclophosphamide 200 mg/m2 is to be administered as a 30 minute IV infusion one day prior to GVAX for a total of 8 doses. Other Names: Cytoxan CY Other Names: CY Drug: GVAX 5E8 cells is to be administered one day after CY, pembrolizumab, and IMC-CS4/ LY3022855 for a total of eight doses. Other Names: Pancreatic cancer vaccine Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo Other Names: Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo Drug: Pembrolizumab 200 mg will be administered as a 30 minute IV infusion one day prior to the GVAX pancreas vaccine for a total of 18 doses. Other Names: MK-3475 KEYTRUDA Other Names: MK-3475, KEYTRUDA® Drug: IMC-CS4 75 mg for dose level 1 and 100 mg at dose level 2 will be administered (Day 1, Day 8 and Day 15) as a 30 minute(s) IV infusion one day prior to GVAX pancreas vaccine for a total 18 doses. Other Names: LY3022855

Arm

Intervention/Treatment

Experimental: Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4

Drug: Cyclophosphamide

200 mg/m2 is to be administered as a 30 minute IV infusion one day prior to GVAX for a total of 8 doses. Other Names: Cytoxan CY

Other Names:

Drug: GVAX

5E8 cells is to be administered one day after CY, pembrolizumab, and IMC-CS4/ LY3022855 for a total of eight doses. Other Names: Pancreatic cancer vaccine Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo

Other Names:

Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo

Drug: Pembrolizumab

200 mg will be administered as a 30 minute IV infusion one day prior to the GVAX pancreas vaccine for a total of 18 doses. Other Names: MK-3475 KEYTRUDA

Other Names:

MK-3475, KEYTRUDA®

Drug: IMC-CS4

75 mg for dose level 1 and 100 mg at dose level 2 will be administered (Day 1, Day 8 and Day 15) as a 30 minute(s) IV infusion one day prior to GVAX pancreas vaccine for a total 18 doses.

Other Names:

LY3022855

Outcome Measures

Primary Outcome Measures

CD8 T cell density in the primary tumor after neoadjuvant administration of combination immunotherapy by immunohistochemistry (IHC) [2 years]
Number of participants experiencing study drug-related toxicities [2 years]

Secondary Outcome Measures

Overall survival (OS) [2 years]
Disease free survival (DFS) [2 years]
Objective response rate (ORR) by immune-related RECIST criteria (irRC) [2 years]
Surgical resectability rate of borderline resectable pancreatic cancer (BRPC) [2 years]
Pathologic response rate of patients with BRPC [2 years]
Progression free survival (PFS) [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Have histologically or cytologically proven adenocarcinoma of the pancreas.
Patient's acceptance to have a core biopsy.
Presence of at least one measurable lesion.
Must not have metastatic disease.
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 10.1.2 for the evaluation of measurable disease.
Must have received last dose of stereotactic body radiotherapy no longer than 28 days prior to enrollment.
Must have received last dose of chemotherapy at least 14 days or longer prior to entry into the study.
Age >18 years.
ECOG performance status 0-1.
Patient's blood, kidney and liver function must within normal limits
Must use an acceptable form of birth control while on study.
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Currently is participating or has participated in a study using any investigational therapy within the past 28 days or is currently using an investigational device.
Major surgery 28 days prior to study entry excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement.
Used any systemic steroids, immunosuppressant medications and anti-neoplastic treatment in the past 14 days.
Prior treatment with immunotherapy agents (including, but not limited to: IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies).
Used any growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug administration. Use of such agents while on study is also prohibited.
Received any prophylactic vaccine within 14 days of first dose of study drug or received a live vaccine within 30 days of study treatment.
Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, psychological, immune or other medical conditions.
History of any autoimmune disease: inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g., Wegener's Granulomatosis), CNS or motor neuropathy considered to be of autoimmune origin (e.g., Guillian-Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis). Patients with thyroid disease will be allowed.
Has history of (non-infectious) pneumonitis that required steroids, history or evidence of interstitial lung disease or active, non-infectious pneumonitis.
Has a pulse oximetry < 92% on room air.
Evidence of ascites on imaging.
Requires the use of home oxygen.
Have known history of infection with HIV, hepatitis B, or hepatitis C.
Have been diagnosed with another cancer in the past 5 years (except for superficial bladder cancer, non-melanoma skin cancers, or a low grade prostate cancer not requiring therapy)
History of severe hypersensitivity reaction to any monoclonal antibody.
Known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX pancreas vaccine.
Pregnant or breastfeeding women.
Positive pregnancy test during the study.
Women sexually active with a fertile man and of childbearing potential unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 120 days after the last dose of study drug.
Unwilling or unable to follow the study schedule for any reason.