This is a prospective, open-label therapeutic interventional investigation designed to interrogate the efficacy and safety of individualized matched therapies in patients with pancreatic cancer at high risk of disease recurrence post-surgery.

This is a prospective, open-label, therapeutic interventional investigation designed to interrogate the efficacy and safety of personalized matched therapy in pancreatic cancer patients who have completed all intended multimodal therapy, including resection of the pancreatic cancer tumor. Potential participants must have their tumor tissue or blood molecularly profiled with the results discussed by the Molecular Tumor Board, whether convened in person, virtually (e.g., WebEx), or in an electronic forum (e.g., email). Only those patients who agree to receive the Molecular Tumor Board-recommended matched therapy (i.e., study treatment) will be eligible and enrolled on the study.

Inclusion Criteria:

1. Age ≥18 years.

2. Pathologically confirmed pancreatic cancer (excluding neuroendocrine histology).

3. Pancreatic tumor is surgically removed and

   1. patient has received multimodal therapy (neoadjuvant, sandwich or adjuvant chemotherapy ± radiation) or
   2. patient is ineligible for or refuses multimodal therapy.

4. Patient has one of the following:

   1. Post-surgical cancer antigen (CA) 19-9 elevation (> 35 U/mL at least 6 weeks post-surgical resection) in the setting of bilirubin < 2 mg/dL (unless bilirubin elevation is consistent with Gilbert's syndrome) OR
   2. High-risk pathological features, defined as positive surgical margin or lymph node involvement in cancer.

5. Patient has no definitive measurable disease recurrence or metastatic disease at the time of first post-surgical imaging (in those with high-risk pathological features) or within four weeks of elevated CA 19-9 value as evidenced by appropriate imaging.

6. Laboratory values:

   1. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L.
   2. Platelet count ≥ 75,000/mm^3 (125 × 109/L).
   3. Hemoglobin (Hgb) ≥ 8 g/dL.
   4. aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT), alanine transaminase (ALT) serum glutamate-pyruvate transaminase (SGPT) ≤ 5 × upper limit of normal range (ULN).

7. Eastern Cooperative Oncology Group (ECOG) Performance Status < 3.

8. At the time of treatment, patient should be off other anti-tumor agents for at least five half-lives of the agent or three weeks from the last day of treatment, whichever is shorter.

9. Able to swallow and retain oral medication, if needed.

10. Pregnancy It is not known what effects matched therapy has on human pregnancy or development of the embryo or fetus. Therefore, female subjects participating in this study should avoid becoming pregnant, and male subjects should avoid impregnating a female partner. Nonsterilized female subjects of reproductive age and male subjects should use effective methods of contraception through defined periods during and after study treatment as specified below.

    Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

    • Not a female of childbearing potential (FCBP), defined as all female patients that were not in post-menopause for at least one year or are surgically sterile, OR
    • An FCBP must have a negative serum pregnancy test and agree to use at least one form of pregnancy prevention during the study for at least one month after treatment discontinuation unless otherwise noted by the agent(s) USPI, which the FCBP must follow.

    Male participants: A male participant, even if surgically sterilized (i.e., status post vasectomy), must use a form of barrier pregnancy prevention approved by the investigator or treating physician during the study and for at least one month after treatment discontinuation and refrain from donating sperm during this period unless otherwise noted by the agent(s) USPI, which the male participant must follow.

11. Patient must be presented at the Molecular Tumor Board (MTB) and agree to receive the MTB-recommended therapy.

12. Ability to understand a written informed consent document, and the willingness to sign it.

    1. Patients presented at the MTB prior to signing consent are eligible to be on study. Patients do not need to be presented again at the MTB prior to starting therapy on trial unless six months elapse between consent and start of study treatment.

Exclusion Criteria:

A potential study subject who meets any of the following exclusion criteria is ineligible to participate in the study.

1. CA 19-9 non-producers, unless high-risk pathological features present.
2. Receiving concomitant investigational agent(s) for pancreatic ductal adenocarcinoma (PDAC).
3. Radiographic evidence of metastatic disease.
4. Inability to ingest study drugs by mouth.
5. Diarrheal bowel movements > 6 per day postoperatively on maximal medical therapy.
6. Patient has active, untreated, or uncontrolled bacterial, viral, or fungal infection(s) requiring systemic intravenous therapy.
7. Patient has undergone or planned major surgery other than diagnostic surgery (i.e., surgery done to obtain a biopsy for diagnosis without removal of an organ) within four weeks prior to Day 1 of study therapy.
8. Patient has a history of allergy or hypersensitivity to the study drug(s) or any of the excipients.
9. Uncontrolled concurrent illness, including, but not limited to, unstable angina pectoris, uncontrolled and clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
10. Is pregnant or breastfeeding or any patient with childbearing potential not using adequate pregnancy prevention.