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

NCT03153410 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: J1766IRB00130267
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Keywords

Pancreas vaccine; immunotherapy; antibody; PD-1; IMC-CS4; Pembrolizumab; GVAX; Borderline Resectable; CY; Cyclophosphamide; Adenocarcinoma; Neoplasms

Outcome Measures

Primary Outcomes (2)

• Number of Patients With a Treatment-related Immunologic Effect

  Treatment-related immunologic effect is defined as an 80% or greater increase in the number of CD8+ T cells (and at least 1.8 times the baseline median absolute deviation) in surgically resected tumor tissue in comparison to the baseline biopsy in subjects that received at least 1 dose of neoadjuvant combination immunotherapy and underwent a R0, R1, or R2 surgical resection.

  8 weeks

• 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

  Number of subjects that experienced a grade 3 or higher study drug related adverse event

  25 months

Secondary Outcomes (5)

• Overall Survival (OS)

  44 months

• Disease Free Survival (DFS)

  37 months

• Immune-related Objective Response Rate (irORR)

  Up to 10 weeks from baseline irRC read

• Surgical Resectability Rate

  8 weeks

• Pathologic Response Rate

  8 weeks

Study Arms (1)

Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4

EXPERIMENTAL

Drug: Cyclophosphamide; Drug: GVAX Pancreas Vaccine (GVAX); Drug: Pembrolizumab; Drug: IMC-CS4

Interventions

Cyclophosphamide DRUG

200 mg/m\^2, intravenous (IV) infusion 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.

Also known as: CY, Cytoxan

Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4

GVAX Pancreas Vaccine (GVAX) DRUG

5x10\^8 cells, six intradermal (ID) injections 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.

Also known as: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine

Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4

Pembrolizumab DRUG

200 mg, intravenous (IV) infusion 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.

Also known as: MK-3475,, KEYTRUDA®

Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4

IMC-CS4 DRUG

75 mg (dose level 1) or 100 mg (dose level 2), intravenous (IV) infusion 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.

Also known as: LY3022855

Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Merck Sharp & Dohme LLC: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma; Neoplasms

Interventions

Cyclophosphamide; pembrolizumab; LY3022855

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Ana De Jesus-Acosta, MD
• Organization: SKCCC Johns Hopkins Medical Institution

adejesu1@jhmi.edu

443-287-0411

Study Officials

• Ana DeJesus, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2017
• First Posted: May 15, 2017
• Study Start: September 27, 2018
• Primary Completion: March 9, 2022
• Study Completion: August 29, 2023
• Last Updated: January 9, 2025
• Results First Posted: October 15, 2024

Record last verified: 2024-12

Locations

US (1)