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.

Cyclophosphamide

GVAX pancreatic cancer

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.

Nivolumab

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.

Urelumab

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.

BMS-986253

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Colorectal cancer: Tunlametinib 6/9mg bid+ cetuximab β 500mg/m2

Colorectal cancer: Tunlametinib + cetuximab β

Pancreatic cancer: Tunlametinib 6/9mg+ cetuximab β 500mg/m2

Pancreatic cancer: Tunlametinib + cetuximab β

Pancreatic cancer: Tunlametinib 6/9mg bid +Nimotuzumab 400mg

Pancreatic cancer: Tunlametinib +Nimotuzumab

Patients will include those who have undergone pancreatic imaging with MRI or CT or EUS and found to have one or more pancreatic imaging abnormalities such as a pancreatic cyst consistent with an intraductal papillary mucinous neoplasm (IPMN) or parenchymal changes consistent with pancreatic intraepithelial neoplasia (PanIN). additionally patients with:

1. familial pancreatic cancer relatives
2. germline mutation carriers with an estimated lifetime risk of pancreatic cancer of \~10% or higher
3. germline mutation carriers with an estimated lifetime risk of pancreatic cancer of \~5%, all detailed in Section 3.1.1. These patients must also (as defined in Section 3.1.2).

1. KRAS peptide vaccine with poly-ICLC adjuvant will be administered on Prime week 1, 3, and 5. Boost vaccinations with will be administered at week 13. All subjects will return to the study site approximately 28 days (+ 7 days) after the last vaccination for an End of Treatment (EOT) and safety evaluation.
2. Drug: up to 1.8 mg KRAS peptide vaccine + 0.5mg Poly-ICLC

Cohort A: Patients at high risk of developing pancreatic cancer.

Patients must have clinical, radiographic, or histologic evidence of a pancreatic cystic neoplasm with high-risk features warranting surgical resection per the discretion of the treating hepatobiliary surgeon. In addition, cyst fluid analysis must demonstrate the presence of one of the six KRAS mutations included in the study vaccine. Germline mutation testing or a positive family history of pancreatic cancer is not required for enrollment in Cohort B.

Patients will receive KRAS peptide vaccine with poly-ICLC adjuvant as two prime vaccinations on weeks 1 and 2. Surgery is considered standard of care. Surgery will occur at the discretion of the treating hepatobiliary surgeon and is not dictated by this protocol. Subjects will return to the study site approximately at week 4 (+ 7 days) for a safety evaluation prior to surgery. Subjects will have an End of Treatment (EOT) visit at study Week 8 (+ 7 days).

Cohort B: Patients must have evidence of a pancreatic cystic neoplasm

Colleen Apostol, RN

Nilofer Azad, MD

Participants in the intervention Arm will have their blood samples tested on the Avantect test within prioritised timeframe. The "detected" Avantect test results will be shared with the participants and their General Practitioners (GPs) to allow for further MRI or CT investigations by the local clinical team.

Avantect Pancreatic Cancer Test

Control arm participants will have their blood samples collected but they will not be tested on the Avantect test. Participants will receive the current standard of care for diabetes management. Blood samples will be used for potential future Avantect testing and/ or future research.

University Hospital Southampton NHS Foundation Trust

Anson-Wisniewska

Two interventions are performed:

1. Have Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score calculated, and if Score is \>0,
2. Have abdominal imaging performed.

ENDPAC is a model to risk-stratify patients with new onset diabetes and hyperglycemia for PDAC. Score is calculated using i) age, ii) change, over past year, in body weight and iii) change, over past year, in glucose/HbA1c values obtained from the electronic medical record.

Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score

Using computerized tomography (CT) scan or magnetic resonance imaging (MRI), if CT scan is contra-indicated, patients with a high ENDPAC score (\>0) are approached for informed consent to participate in the imaging intervention. Imaging (CT scan) is performed at up to two time points, study baseline and approximately 3-9 months following the first imaging study.

Abdominal imaging

Passive follow-up by electronic medical record for study endpoints of pancreatic cancer diagnosis.

200 mg/m2 is to be administered as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg/m2 as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 6 months for an additional 4 doses.

2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells is to be administered one day after CY and pembrolizumab for a total of 8 doses. In the extended treatment phase, eligible patients may receive 2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells administered one day after CY every 6 months for an additional 4 doses.

GVAX Pancreatic Cancer Vaccine

200 mg will be administered as a 30 minute IV infusion one day prior to the GVAX pancreas vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg as a 30 minute IV infusion every 21 days for an additional 9 doses.

Pembrolizumab

Patients will receive SBRT (6.6 Gy for 5 days) with the second dose of combined immunotherapy (CY/Pembrolizumab/GVAX Pancreas Vaccine).

SBRT

Each subject can undergo to up to 3 blood draws; at the time of enrollment (T0), at 6 months (T1) and 12 months (T2) from diabetes diagnosis. After 24 months from diabetes diagnosis, a review of the electronic medical records (EMR) will be performed for all subjects with a "not detected" test result.

Blood collection and pancreatic cancer early detection testing with return of results

Early detection pancreatic cancer test

A pre-specified number of cases with test results "not detected" will be randomly selected, gender ratio and age matched to subjects with test results "detected" and will undergo MRI imaging at T0 (n=226), at T1 (n=208 ) at T2 (n=208 ) and 24 months (n=208) from diabetes diagnosis.

Blood collection and pancreatic cancer early detection testing with return of results and MRI Imaging

Early detection pancreatic cancer test and MRI Imaging

Participants undergo peripheral blood collection for the Enzeavour Pancreatic Cancer assay as part of a routine health checkup or organized cancer screening visit. Participants with a positive assay result, defined as an Enzeavour Score greater than 0.369, are referred for diagnostic work-up, including MRCP, EUS, or contrast-enhanced CT, as clinically indicated.

A blood-based diagnostic assay that quantifies the activity of three specific enzymes at a single-molecule level. Four biomarkers derived from these measurements are integrated into a composite Enzeavour Score using a predefined discriminant function. Participants with a score above the pre-specified cut-off of 0.369 are considered test-positive and referred for diagnostic work-up.

사이클로포스파미드, GVAX 췌장암, 니볼루맙, 우렐루맙, BMS-986253

대장암: 툰라메티닙 + 세툭시맙 β, 췌장암: 툰라메티닙 + 세툭시맙 β, 췌장암: 툰라메티닙 + 니모투주맙

A군: 췌장암 발병 위험이 높은 환자, B군: 췌장 낭성 신생물이 있는 환자

아반텍 췌장암 검사

췌장암 진단을 위한 신규 발병 당뇨병 점수 향상(ENDPAC), 복부 영상

사이클로포스파미드, GVAX 췌장암 백신, 펨브롤리주맙, SBRT

췌장암조기 발견 검사, 췌장암 조기 발견 검사 및 MRI 영상 촬영

엔제아버 췌장암 검사