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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Nivolumab
* Drug: Ipilimumab
* Drug: GVAX Pancreas Vaccine
* Drug: CRS-207
* Drug: CRS-207


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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 Infection with HIV or hepatitis B or C at screening Significant heart disease 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 Are pregnant or breastfeeding. Have rapidly progressing disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207<br> | Drug: Cyclophosphamide<br>* 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.<br>* Other names: CY;Drug: Nivolumab<br>* 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.<br>* Other names: anti-PD-1, OPDIVO;Drug: Ipilimumab<br>* 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.<br>* Other names: YERVOY®;Drug: GVAX Pancreas Vaccine<br>* 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.<br>* Other names: GVAX, PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine;Drug: CRS-207<br>* 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.<br>|
| Experimental: Arm B: Nivolumab, Ipilimumab, CRS-207<br> | Drug: Nivolumab<br>* 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.<br>* Other names: anti-PD-1, OPDIVO;Drug: Ipilimumab<br>* 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.<br>* Other names: YERVOY®;Drug: CRS-207<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Events (AEs) | When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject. Laboratory abnormalities that were asymptomatic and not clinically significant were excluded. | 21 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CY, Cyclophosphamide, Pancreatic Vaccine, GVAX, Nivolumab, Vaccine, Ipilimumab, CRS-207, Immunotherapy, PD-1, Adenocarcinoma, Carcinoma, Neoplasms