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

• ClinicalTrials.gov Identifier: NCT03190265
• Recruitment Status: Active, not recruiting
• First Posted: June 16, 2017
• Last Update Posted: March 25, 2022
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Aduro Biotech, Inc.; Bristol-Myers Squibb
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information

• First Submitted Date: June 15, 2017
• First Posted Date: June 16, 2017
• Last Update Posted Date: March 25, 2022
• Actual Study Start Date: December 14, 2017
• Estimated Primary Completion Date: September 1, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 15, 2017): Objective response rate (ORR) using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) [ Time Frame: 4 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 15, 2017)

• Number of participants experiencing study drug-related toxicities [ Time Frame: 4 years ]
• Overall survival (OS) [ Time Frame: 4 years ]
• Progression free survival (PFS) [ Time Frame: 4 years ]
• Duration of response (DOR) [ Time Frame: 4 years ]
• Time to progression (TTP) [ Time Frame: 4 years ]
• Tumor marker kinetics (CA19-9) [ Time Frame: 4 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer
• Official Title: A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cyclophosphamide) in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• Drug: Cyclophosphamide
  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.
  Other Name: CY
• Drug: Nivolumab
  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.
  Other Name: anti-PD-1, OPDIVO
• Drug: Ipilimumab
  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.
  Other Name: YERVOY®
• Drug: GVAX Pancreas Vaccine
  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.
  Other Name: GVAX, PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine
• Drug: CRS-207
  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.
• Drug: CRS-207
  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 1-6.

Study Arms

• Experimental: CY, Nivolumab, Ipilimumab, GVAX, CRS-207
  Interventions:

  • Drug: Cyclophosphamide
  • Drug: Nivolumab
  • Drug: Ipilimumab
  • Drug: GVAX Pancreas Vaccine
  • Drug: CRS-207
• Experimental: Nivolumab, Ipilimumab, CRS-207
  Interventions:

  • Drug: Nivolumab
  • Drug: Ipilimumab
  • Drug: CRS-207

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: June 15, 2017): 63
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 1, 2022
• Estimated Primary Completion Date: September 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age ≥18 years.
2. Have histologically or cytologically proven adenocarcinoma of the pancreas.
3. Have metastatic disease.
4. Have disease progression.
5. Patients with the presence of at least one measurable lesion.
6. 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).
7. ECOG performance status 0 or 1
8. Life expectancy of greater than 3 months.
9. Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
10. Must use acceptable form of birth control while on study.
11. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. Known history or evidence of brain metastases.
2. Had surgery within the last 28 days
3. Had chemotherapy, radiation, or biological cancer therapy within the last 14 days
4. Have received a prophylactic vaccine within 14 days or received a live vaccine within 30 days of planned start of study therapy.
5. Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2,or anti-CTLA4
6. Systemic steroids within the last 14 days
7. Use more than 2 g/day of acetaminophen.
8. Patients on immunosuppressive agents.
9. Patients receiving growth factors within the last 14 days
10. Known allergy to both penicillin and sulfa.
11. Severe hypersensitivity reaction to any monoclonal antibody.
12. Have artificial joints or implants that cannot be easily removed
13. Have any evidence of clinical or radiographic ascites.
14. Have significant and/or malignant pleural effusion
15. Have had a new pulmonary embolism, extremity deep venous thromboembolism, or portal vein thrombosis within 2 months of study treatment
16. Infection with HIV or hepatitis B or C at screening
17. Significant heart disease
18. Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures
19. Are pregnant or breastfeeding.
20. Have rapidly progressing disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03190265
• Other Study ID Numbers: J1790; IRB00137389 ( Other Identifier: Johns Hopkins University )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Responsible Party: Same as current
• Current Study Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Study Sponsor: Same as current

Collaborators

• Aduro Biotech, Inc.
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Dung Le, MD; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• PRS Account: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Verification Date: March 2022