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

BOLD-100 is a novel, targeted anti-cancer therapy which is an intravenously administered small molecule drug. In a previous Phase 1 study (NCT01415297) BOLD-100 showed low toxicity with minimal hematological issues as well as some potential anti-tumour activity. The lack of observed hematological toxicity and neurotoxicity position BOLD-100 well for use in combination with a broad range of standard-of-care (SOC) chemotherapy regimens.

This is a prospective, multicenter non-randomized Phase 1b/2a dose escalation & expanded cohort study of BOLD-100 in patients with advanced gastrointestinal malignancies (colorectal, pancreatic, gastric cancers, and cholangiocarcinoma) receiving standard-of-care FOLFOX chemotherapy. Enrollment in Arms I - VI is closed to enrollment.

Colorectal cancer (ARM VII) for patients who are oxaliplatin naïve and have received only 1 prior line of therapy in the metastatic setting. Within this arm, participants will be randomized to one of two dose levels of BOLD-100 - either 500 mg/m2 or 625 mg/m2 in combination with FOLFOX or FOLFOX alone, in a 1:1:1 ratio. Participants enrolled into Arm VII will complete quality of life questionnaires examining general quality of life and neuropathy associated quality of life parameters.

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)