The purpose of this study is to see if using Patient Derived Organoids (PDO) to choose a drug for the treatment of pancreatic cancer individually for each patient is useful. The study will look at the number of participants who have a response to their assigned drug.

PDO is a three-dimensional experimental model grown in a laboratory from patient's tumour tissues. PDO is used to test different drugs and select the drugs that may work for treating the patient's cancer. Researchers will review participants' PDO drug results from other studies from which they participated in and will identify the drug that seem to have the best effect on the PDO model. Participants will be offered to receive that drug during the study.

Inclusion Criteria:

1. Age 18 years or over

2. Ability to understand and willing to sign a written informed consent form in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to screening to document their willingness to participate.

3. Advanced inoperable malignant epithelial pancreatic ductal carcinomas (i.e. primary diagnosis of ductal adenocarcinoma or acinar cell adenocarcinoma, inclusive of all subtypes)

4. Treatment history meeting one of either:

   1. Stable disease or partial response to FOLFIRINOX (leucovorin calcium/folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin) after at least eight cycles of treatment (Cohort B)
   2. Progression of disease after receiving standard of care chemotherapies (Cohort A).

   i. There is no maximum number of prior lines

   ii. Patients with recurrence within six months of adjuvant-intent chemotherapy will be eligible

5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

6. Life Expectancy of greater than 12 weeks

7. Patients must have acceptable organ function

8. Patients must have baseline hepatitis B screening. If they have a positive surface antigen the case will discussed with the hepatologist to determine if therapy is indicated. This does not exclude them from study.

9. Patients must agree to use effective contraceptive methods for the period required by the study.

10. Patients must have measurable disease

11. Patient-derived organoid is sensitive to a drug listed for this study, defined by

    1. Consensus agreement in molecular tumor boards, considering the totality of the genomic and organoid data, and the safety profile of the drug, and the clinical situation
    2. Sensitivity to a drug chosen for the study, based on

    i. IC50 < Cmax (maximum plasma concentration) ii. Area under the curve (AUC) < 30th percentile of cohort iii. Individual assay fulfills quality control metrics c. Matched clinical scenario (maintenance versus treatment) as outlined in this protocol.

12. Able to swallow and tolerate oral medication (as applicable)

Exclusion Criteria:

1. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
2. Patient received last dose of chemotherapy within 21 days prior to Cycle 1 Day 1.
3. Patients with ongoing toxicity ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2, other than peripheral neuropathy, related to prior anti-tumour treatment.
4. Patients with ongoing peripheral neuropathy of ≥ CTCAE grade 3 will be excluded.
5. Patients concurrently receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (e.g. megestrol acetate, bisphosphonates). These medications must have been started ≥ one month prior to enrolment in this study.
6. Patients with a history of a severe allergic reaction attributed to compounds of similar or biologic composition to the PDO matched drug may be excluded if assessed by the investigator and determined to be unsafe to proceed.
7. Patients may be on warfarin, low molecular weight heparin or direct factor Xa inhibitors, unless such therapies are prohibited by drug-specific ineligibility criteria.
8. Patients with known active progressive brain metastases. Patients with previously treated brain metastases are eligible, provided that the patient has not experienced a seizure or had a clinically significant change in neurological status within one month prior to screening. All patients with previously treated brain metastases must be stable (clinically and radiologically) for at least one month after completion of treatment and either off steroid treatment or only taking physiological doses of steroids prior to the screening step.
9. Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure.
10. Patients with known left ventricular ejection fraction (LVEF) < 40 % as determined by a multigated acquisition (MUGA) scan or echocardiogram.
11. Patients with stroke (including TIA) or acute myocardial infarction within three months prior to the screening step.
12. Patients with acute gastrointestinal bleeding within one month prior to the screening step.
13. Patients with any other clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements including, but not limited to ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations.
14. Lactating and nursing women.
15. Patients who do not meet drug-specific eligibility requirements for the drug selected by the treating physician.