Pancreatic Cancer
Conditions
Keywords
CY, Cyclophosphamide, Pancreatic Vaccine, GVAX, Nivolumab, Vaccine, Ipilimumab, CRS-207, Immunotherapy, PD-1, Adenocarcinoma, Carcinoma, Neoplasms
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.
Interventions
DRUGCyclophosphamide
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.
DRUGNivolumab
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.
DRUGIpilimumab
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.
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.
DRUGCRS-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.
Sponsors
Aduro Biotech, Inc.
Bristol-Myers Squibb
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) | 18 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Events (AEs) | 21 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207 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.
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.
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.
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.
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. | 31 |
| Arm B: Nivolumab, Ipilimumab, CRS-207 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.
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.
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. | 30 |
| Total | 61 |
Baseline characteristics
| Characteristic | Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207 | Arm B: Nivolumab, Ipilimumab, CRS-207 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 10 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 20 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 28 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 28 Participants | 55 Participants |
| Sex: Female, Male Female | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Male | 18 Participants | 16 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 28 / 30 | 27 / 27 |
| other Total, other adverse events | 30 / 30 | 27 / 27 |
| serious Total, serious adverse events | 24 / 30 | 21 / 27 |
Outcome results
Primary
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.
Time frame: 18 months
Population: Only 29/30 participants in Arm A were evaluable for this endpoint. One participant was not evaluable after they discontinued prior to their first scan for a reason other than toxicity or progression.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: CY, Nivolumab, Ipilimumab, Pancreas GVAX, CRS-207 | Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) | 0 Participants |
| Arm B: Nivolumab, Ipilimumab, CRS-207 | Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) | 2 Participants |
Secondary
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.
Time frame: 21 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: CY, Nivolumab, Ipilimumab, Pancreas GVAX, CRS-207 | Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Events (AEs) | 10 Participants |
| Arm B: Nivolumab, Ipilimumab, CRS-207 | Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Events (AEs) | 10 Participants |