This is a multi-cohort proof of concept study involving patients with metastatic gastrointestinal cancers. In the first cohort of treatment-naïve patients, the investigators intend to create cancer organoids for 100 subjects. Then, the investigators intend to evaluate ex-vivo prediction of treatment outcomes using QPOP (see section 4.0 for detailed sample size calculation).

Patients enrolled on study will undergo a fresh biopsy of tumour lesion to obtain cells that will be used to generate patient-derived tumour organoids. These patients will go on to receive standard of care first-line chemotherapy +/- targeted therapy. Organoids will then be subjected to up to a 14-drug panel screening. The drugs in the respective drug panel have been shown to have activity in the respective cancers and would be used in the standard-of-care setting by treating physicians.

Hypothesis: Ex-vivo sensitivity testing on patient derived tumour organoids using QPOP can identify drug combinations which may have clinical efficacy against metastatic gastrointestinal cancer.

Specific aim 1: To grow patients' gastrointestinal tumour-derived organoids.

Specific aim 2: To perform ex-vivo drug sensitivity testing on patient derived tumour organoids using QPOP for metastatic gastrointestinal cancers.

Specific aim 3: Asses the efficacy of phenotype directed therapy using QPOP to assign treatment after progression of standard of chemo for gastric cancer.

Inclusion Criteria:

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Patients may be included in the study only if they meet the following criteria:

1. Treatment naïve patient with gastrointestinal cancers (i.e. oesophageal, gastro-oesophgeal, gastric, small bowel, colorectal, hepatocellular, pancreatic and biliary tract) fit and planned for first line treatment, OR

2. Chemo-refractory patients with GI cancers deemed by investigator to be fit for clinical trial

3. Age ≥ 21 years

4. ECOG PS 0-1

5. At least 1 tumour lesion amenable to fresh biopsy

6. At least 1 measurable tumour lesion based on RECIST v 1.1 criteria

7. Estimated life expectancy of at least 24 weeks

8. Adequate organ function , including:

   1. Pre-biopsy

      o Bone marrow:

      • Absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x 109/L
      • Platelets ≥ 100 x 109/L
      • Pro-Thrombin within ULN
      • Hemoglobin ≥ 8 x 109/L

   2. Pre-treatment

      • Bone marrow:

        • Absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x 109/L
        • Platelets ≥ 100 x 109/L
        • Hemoglobin ≥ 8 x 109/L

      • Hepatic:

        • Bilirubin ≤ 1.5 x upper limit of normal (ULN),
        • ALT or AST ≤ 2.5x ULN, (or ≤ 5 X with liver metastases)

      • Renal:

        • Creatinine ≤ 1.5x ULN

9. Signed informed consent from patient or legal representative

10. Able to comply with study-related procedures.

11. Recovery from prior toxicity to G1, excluding alopecia.

Exclusion Criteria:

• There are no specific exclusion criteria if patients meet the inclusion criteria

At least 20 patients with gastric cancer, and 80 patients with other GI cancers will be first be recruited.