Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer

NCT03190265 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: J1790IRB001373895P01CA247886-02
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to study the safety and clinical activity of nivolumab and ipilimumab in combination with either sequential administration of CY/GVAX pancreas vaccine followed by CRS-207 (Arm A) or with administration of CRS-207 alone (Arm B) in patients with pancreatic cancer.

Conditions

Pancreatic Cancer

Keywords

CY; Cyclophosphamide; Pancreatic Vaccine; GVAX; Nivolumab; Vaccine; Ipilimumab; CRS-207; Immunotherapy; PD-1; Adenocarcinoma; Carcinoma; Neoplasms

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)

  Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not included in the analysis.

  18 months

Secondary Outcomes (1)

• Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Events (AEs)

  21 months

Study Arms (2)

Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207

EXPERIMENTAL

Drug: Cyclophosphamide; Drug: Nivolumab; Drug: Ipilimumab; Drug: GVAX Pancreas Vaccine; Drug: CRS-207

Arm B: Nivolumab, Ipilimumab, CRS-207

EXPERIMENTAL

Drug: Nivolumab; Drug: Ipilimumab; Drug: CRS-207

Interventions

Cyclophosphamide DRUG

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Cyclophosphamide (200 mg/m2) will be administered IV on day 1 of Cycles 1 and 2.

Also known as: CY

Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207

Nivolumab DRUG

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Nivolumab (360 mg) will be administered IV on day 1 of Cycles 1-6.

Also known as: anti-PD-1, OPDIVO

Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207; Arm B: Nivolumab, Ipilimumab, CRS-207

Ipilimumab DRUG

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Ipilimumab (1 mg/kg) will be administered IV on Day 1 of Cycles 1, 3, and 5.

Also known as: YERVOY®

Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207; Arm B: Nivolumab, Ipilimumab, CRS-207

GVAX Pancreas Vaccine DRUG

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Vaccine will be administered on Day 2 of Cycles 1 and 2.

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

Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207

CRS-207 DRUG

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 109 CFU) will be administered IV on Day 2 of Cycles 3-6.

Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Have histologically or cytologically proven adenocarcinoma of the pancreas.
• Have metastatic disease.
• Have disease progression.
• Patients with the presence of at least one measurable lesion.
• Patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).
• ECOG performance status 0 or 1
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Known history or evidence of brain metastases.
• Had surgery within the last 28 days
• Had chemotherapy, radiation, or biological cancer therapy within the last 14 days
• Have received a prophylactic vaccine within 14 days or received a live vaccine within 30 days of planned start of study therapy.
• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2,or anti-CTLA4
• Systemic steroids within the last 14 days
• Use more than 2 g/day of acetaminophen.
• Patients on immunosuppressive agents.
• Patients receiving growth factors within the last 14 days
• Known allergy to both penicillin and sulfa.
• Severe hypersensitivity reaction to any monoclonal antibody.
• Have artificial joints or implants that cannot be easily removed
• Have any evidence of clinical or radiographic ascites.
• Have significant and/or malignant pleural effusion
• Have had a new pulmonary embolism, extremity deep venous thromboembolism, or portal vein thrombosis within 2 months of study treatment

Sponsors & Collaborators

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

Study Sites (1)

Johns Hopkins SKCCC

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms

Interventions

Cyclophosphamide; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; 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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dung Le, MD
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

dle@jhmi.edu

443-287-0002

Study Officials

• Dung Le, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: June 15, 2017
• First Posted: June 16, 2017
• Study Start: December 14, 2017
• Primary Completion: August 3, 2022
• Study Completion: August 23, 2023
• Last Updated: August 7, 2024
• Results First Posted: July 10, 2023

Record last verified: 2024-08

Locations

US (1)