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

Inclusion Criteria

• Be 18 years or older.
• Be male or non-pregnant females who agree to comply with applicable contraceptive requirements of the protocol.
• Histologically and/or cytologically confirmed gastrointestinal tumours that are metastatic or unresectable. (ARM VII): Patients must have received only 1 prior line of therapy in the metastatic setting.
• Have measurable disease according to RECIST v1.1.
• Have an anticipated survival of at least 16 weeks.
• Be ambulatory, with an ECOG performance score of 0 or 1.
• Have adequate organ function.
• Be on stable doses of any drugs that may affect hepatic drug metabolism or renal drug excretion.
• Be fully informed about their illness and the investigational nature of the study protocol, and sign a REB-approved Informed Consent Form (ICF).
• (ARM VII): BRAF wild-type tumour status.

Exclusion Criteria

• Neuropathy > grade 2
• Previous intolerance to or significant reaction secondary to fluorouracil or oxaliplatin.
• Cerebrovascular accident within the past 6 months before the start of treatment.
• History or presence of central nervous system (CNS) metastasis or leptomeningeal tumours.
• Any serious medical conditions that might be aggravated by treatment or limit compliance.
• Any history of serious cardiac illness.
• Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in the past 6 months before the start of treatment.
• Any other known malignancy within 3 years before the start of treatment.
• Active gastrointestinal tract disease with malabsorption syndrome.
• Non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease.
• Treatment with radiation therapy or surgery within 4 weeks prior to starting treatment.
• Recent history of weight loss > 10% of current body weight in past 3 months before the start of treatment.
• HIV-positive subjects on combination anti-retroviral therapy due to the potential for PK interactions with the study agent.
• Concurrent use of another investigational therapy or anti-cancer therapy within 4 weeks before the start of treatment.
• Currently breastfeeding
• Dihydropyrimidine Dehydrogenase (DPD) deficiency
• Current or prior treatment with potent inhibitors of Dihydropyrimidine Dehydrogenase (DPD)
• (ARM VII): Prior exposure to BOLD-100
• (ARM VII): Subjects with microsatellite-high (MSI-H) Tumours
• (ARM VII): Concurrent monoclonal antibody therapy for mCRC (anti-EGFR, anti-VEGF or anti-HER2)