Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas

NCT02451982 | Active Not Recruiting Phase 2

• 3 other identifiers: J1568IRB00050517R01CA197296
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

This platform trial will evaluate various immunotherapy combinations given in the neo-adjuvant and adjuvant setting in patients with surgically resectable pancreatic ductal adenocarcinoma.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (4)

• IL17A expression

  median IL17A expression in lymphoid aggregates from resected tumor (Arms A and B only)

  4 years

• Intratumoral CD8+CD137+cells

  Fold change of intratumoral CD8+CD137+cells before and after neoadjuvant therapy (Arms B and C only)

  4 years

• Intratumoral granzyme B+PD-1+CD137+ cells

  Percent change of intratumoral granzyme B+PD-1+CD137+ cells in surgical (post-treatment) tissue compared to baseline (pre-treatment) biopsy (Arm D only)

  4 years

• Pathologic Response

  Percent of patients with a response grade of 0-2 (0=complete response 1=marked response, 2=moderate response) at time of surgery

  4 years

Secondary Outcomes (3)

• Drug-Related Adverse Events

  4 years

• Overall Survival

  4 years

• Disease Free Survival

  4 years

Study Arms (4)

Arm A: CY/GVAX alone

EXPERIMENTAL

Patients receive low-dose cyclophosphamide IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide IV on day 0 and the vaccine on day 1. Beginning approximately 1 month after vaccination, patients receive standard adjuvant chemoradiotherapy. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide IV on day 0 and the vaccine on day 1. Treatment with cyclophosphamide and the vaccine repeats every 28 days for 4 courses. Patients will then enter the extended treatment phase where they will receive cyclophosphamide on day 0, and GVAX on day 1 every 12 weeks for another 2 treatments.

Drug: Cyclophosphamide; Biological: GVAX pancreatic cancer

Arm B: CY/GVAX with nivolumab

EXPERIMENTAL

Patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and the vaccine on day 1. Beginning approximately 1 month after vaccination, patients receive standard adjuvant chemoradiotherapy. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and the vaccine on day 1. Treatment with cyclophosphamide, nivolumab, and the vaccine repeats every 28 days for 4 courses. Patients will then enter the extended treatment phase where they will receive nivolumab every 4 weeks for another 6 treatments as well as cyclophosphamide on day 0, and GVAX on day 1 every 12 weeks for another 2 treatments.

Drug: Cyclophosphamide; Biological: GVAX pancreatic cancer; Drug: Nivolumab

Arm C: CY/GVAX with nivolumab and urelumab

EXPERIMENTAL

Patients receive low-dose cyclophosphamide, nivolumab, and urelumab on day 0 and GVAX pancreatic cancer vaccine on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide, nivolumab, and urelumab on day 0 and the vaccine on day 1. Beginning approximately 28 days after vaccination, patients receive standard adjuvant chemoradiotherapy. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide, nivolumab, and urelumab on day 0 and GVAX on day 1. Treatment with cyclophosphamide, nivolumab, urelumab, and the vaccine repeats every 28 days for 4 courses. Patients will then enter the extended treatment phase where they will receive nivolumab and urelumab every 4 weeks for another 6 treatments as well as cyclophosphamide on day 0, and GVAX on day 1 every 12 weeks for another 2 treatments.

Drug: Cyclophosphamide; Biological: GVAX pancreatic cancer; Drug: Nivolumab; Drug: Urelumab

Arm D: BMS-986253 and Nivolumab

EXPERIMENTAL

Patients receive BMS-986253 and nivolumab on day 0 (Cycle 1), 15 days prior to surgery. 6-10 weeks after surgery, patients receive Cycle 2, with nivolumab on day 0 and BMS-986253 on days 0 and 14. Patients then receive standard adjuvant chemoradiotherapy. Approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive 4 additional 28-day cycles of immunotherapy, with Nivolumab on Day 0 and BMS-986253 on Days 0 and 14. Patients will then enter the extended treatment phase where they will receive nivolumab alone every 4 weeks for another 6 treatments.

Drug: Nivolumab; Drug: BMS-986253

Interventions

Cyclophosphamide DRUG

200 mg/m2 IV

Also known as: Cytoxan, CY

Arm A: CY/GVAX alone; Arm B: CY/GVAX with nivolumab; Arm C: CY/GVAX with nivolumab and urelumab

GVAX pancreatic cancer BIOLOGICAL

5x10\^8 cells intradermal injection

Also known as: GVAX, pancreatic tumor vaccine

Arm A: CY/GVAX alone; Arm B: CY/GVAX with nivolumab; Arm C: CY/GVAX with nivolumab and urelumab

Nivolumab DRUG

480 mg IV

Also known as: OPDIVO; BMS-936558; anti-PD1

Arm B: CY/GVAX with nivolumab; Arm C: CY/GVAX with nivolumab and urelumab; Arm D: BMS-986253 and Nivolumab

Urelumab DRUG

8 mg IV

Also known as: BMS-663513; anti-CD137 Agonist

Arm C: CY/GVAX with nivolumab and urelumab

BMS-986253 DRUG

2400 mg IV

Also known as: anti-IL8 antibody; HuMax-IL8

Arm D: BMS-986253 and Nivolumab

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed or clinically-suspected adenocarcinoma of the head, neck, or uncinate process of the pancreas
• Tumor must be surgically resectable
• ECOG Performance Status of 0 to 1
• Adequate organ function as defined by study-specified laboratory tests
• Must agree to use acceptable form of birth control

You may not qualify if:

• Received any type of anti-cancer treatment or immunotherapy for pancreas cancer
• History of autoimmune disease (Graves or Hashimoto's disease, vitiligo, and type I diabetes are allowed)
• Systemically steroid use within 14 days
• Evidence of active infection
• Pregnant or lactating
• Diagnosed with another cancer or myeloproliferative disorder (some exceptions)
• History of severe hypersensitivity reaction to any monoclonal antibody or known component of the study drugs
• Known history of infection with HIV, hepatitis B, or hepatitis C
• Oxygen saturation of \<92% on room air by pulse oximetry
• On home oxygen

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Related Publications (1)

• Heumann T, Judkins C, Li K, Lim SJ, Hoare J, Parkinson R, Cao H, Zhang T, Gai J, Celiker B, Zhu Q, McPhaul T, Durham J, Purtell K, Klein R, Laheru D, De Jesus-Acosta A, Le DT, Narang A, Anders R, Burkhart R, Burns W, Soares K, Wolfgang C, Thompson E, Jaffee E, Wang H, He J, Zheng L. A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma. Nat Commun. 2023 Jun 20;14(1):3650. doi: 10.1038/s41467-023-39196-9.

  PMID: 37339979 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Cyclophosphamide; Nivolumab; urelumab; HuMax-IL8

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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ana De Jesus-Acosta, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: May 22, 2015
• Study Start: March 28, 2016
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-12

Locations

US (1)