BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours

Inclusion Criteria:

1. Be 18 years or older.

2. Be male or non-pregnant females who agree to comply with applicable contraceptiverequirements of the protocol.

3. Histologically and/or cytologically confirmed gastrointestinal tumours that aremetastatic or unresectable. (ARM VII): Patients must have received only 1 prior lineof therapy in the metastatic setting.

4. Have measurable disease according to RECIST v1.1.

5. Have an anticipated survival of at least 16 weeks.

6. Be ambulatory, with an ECOG performance score of 0 or 1.

7. Have adequate organ function.

8. Be on stable doses of any drugs that may affect hepatic drug metabolism or renaldrug excretion.

9. Be fully informed about their illness and the investigational nature of the studyprotocol, and sign a REB-approved Informed Consent Form (ICF).

10. (ARM VII): BRAF wild-type tumour status.

Exclusion Criteria:

1. Neuropathy > grade 2

2. Previous intolerance to or significant reaction secondary to fluorouracil oroxaliplatin.

3. Cerebrovascular accident within the past 6 months before the start of treatment.

4. History or presence of central nervous system (CNS) metastasis or leptomeningealtumours.

5. Any serious medical conditions that might be aggravated by treatment or limitcompliance.

6. Any history of serious cardiac illness.

7. Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in thepast 6 months before the start of treatment.

8. Any other known malignancy within 3 years before the start of treatment.

9. Active gastrointestinal tract disease with malabsorption syndrome.

10. Non-healing wound, fracture, or ulcer, or presence of symptomatic peripheralvascular disease.

11. Treatment with radiation therapy or surgery within 4 weeks prior to startingtreatment.

12. Recent history of weight loss > 10% of current body weight in past 3 months beforethe start of treatment.

13. HIV-positive subjects on combination anti-retroviral therapy due to the potentialfor PK interactions with the study agent.

14. Concurrent use of another investigational therapy or anti-cancer therapy within 4weeks before the start of treatment.

15. Currently breastfeeding

16. Dihydropyrimidine Dehydrogenase (DPD) deficiency

17. Current or prior treatment with potent inhibitors of Dihydropyrimidine Dehydrogenase (DPD)

18. (ARM VII): Prior exposure to BOLD-100

19. (ARM VII): Subjects with microsatellite-high (MSI-H) Tumours

20. (ARM VII): Concurrent monoclonal antibody therapy for mCRC (anti-EGFR, anti-VEGF oranti-HER2)