Clinical trial NCT03153410: Pilot Study With CY, Pembrolizumab, GVAX, and IMC-CS4 (LY3022855) in Patients With Borderline Resectable Adenocarcinoma of the Pancreas
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Pancreatic Cancer
Keywords: Pancreas vaccine
immunotherapy
antibody
PD-1
IMC-CS4
Pembrolizumab
GVAX
Borderline Resectable
CY
Cyclophosphamide
Adenocarcinoma
Neoplasms
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Eli Lilly and Company
First posted: 2017-05-15
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether combining cyclophosphamide (CY), pembrolizumab, GVAX and IMC-CS4 is effective and safe in patients with borderline resectable pancreatic cancer.

Detailed description: This was a single center, open label, pilot study to evaluate the safety and intratumoral immune response of neoadjuvant/adjuvant triplet immunotherapy: CY/GVAX, Pembrolizumab, and IMC-CS4 in patients with resectable or borderline resectable Pancreatic ductal adenocarcinoma.

Patients received the combination of CY/GVAX with pembrolizumab and IMC-CS4 following completion of standard neoadjuvant chemotherapy (with or without radiation). Immunotherapy agents were given prior to and after surgical resection.

Patients receive neoadjuvant immunotherapy consisting of cyclophosphamide and pembrolizumab on day 1, IMC-CS4 on days 1, 8, and 15, and GVAX on day 2 of Cycles 1 and 2 (3 weeks/cycle). Patients will then undergo pancreaticoduodenectomy 2-3 weeks later, followed by standard of care adjuvant chemotherapy at the discretion of the primary oncologist. Patients may then receive 4 cycles (3 weeks/cycle) of adjuvant immunotherapy (same regimen as Cycles 1 and 2). Disease free patients may receive an additional 12 booster cycles (3 weeks/cycle) of immunotherapy consisting of pembrolizumab on day 1 of all 12 booster cycles, as well as cyclophosphamide on day 1 and GVAX on day 2 of the 6th and 12th booster cycle.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients With a Treatment-related Immunologic Effect
timeFrame: 8 weeks
measure: Safety of the Combination of GVAX Pancreas Vaccine (With CY), Pembrolizumab, and a Macrophage Targeting Agent (CSF1R Inhibitor IMC-CS4) in Patients With Resectable or Borderline Resectable Pancreatic Cancer (BRPC) Prior to and Following Surgery
timeFrame: 25 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 44 months
measure: Disease Free Survival (DFS)
timeFrame: 37 months
measure: Immune-related Objective Response Rate (irORR)
timeFrame: Up to 10 weeks from baseline irRC read
measure: Surgical Resectability Rate
timeFrame: 8 weeks
measure: Pathologic Response Rate
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Ana DeJesus, MD
role: PRINCIPAL_INVESTIGATOR
References: