Portfolio prioritization

This is an open-label, dose-escalation, multi-center phase I study evaluating the safety of CF33-hNIS (hNIS - human sodium iodide symporter) administered via two routes of administration, intratumoral (IT) or intravenous (IV), either as a monotherapy or in combination with pembrolizumab or mFOLFOX in patients with metastatic or advanced solid tumors.

CF33-hNIS, a novel chimeric orthopoxvirus, will be administered as a monotherapy or in combination with pembrolizumab or mFOLFOX to assess the safety and efficacy of the treatment regimens as well as immunological changes in the tumour microenvironment.

Patients eligible for treatment in dose escalation IT/IV cohorts include those with any metastatic or advanced solid tumor who have documented radiological progression per RECIST following at least two prior lines of therapy which may have included treatment with an Immune Checkpoint Inhibitor(ICI). For expansion IT and IV cholangiocarcinoma cohort patients, one prior line of systemic chemotherapy in metastatic/advanced setting is required and for patients with targetable tumor mutations, must have also received 1 line of an approved targeted therapy. For expansion IV cholangiocarcinoma cohort, prior treatment with leucovorin calcium, fluorouracil, or oxaliplatin is not permitted.

For IT/IV cohorts, patients will be treated with CF33-hNIS on Day 1 and 8 of Cycle 1 and then on Day 1 of each cycle thereafter. Patients treated with the combination regimen with pembrolizumab will also receive pembrolizumab Day 1 of each cycle beginning with Cycle 2.

For IV cholangiocarcinoma expansion cohort, patients will be treated with CF33-hNIS on Day 3 and Day 17 of each 28 day cycle along with a modified FOLFOX regimen.

Inclusion Criteria:

• Written informed consent from patient or legally authorized representative
• Age ≥ 18 years old on the date of consent
• IT/IV cohorts: Any metastatic or advanced solid tumor with documented radiological progression following at least two prior lines of treatment (which may have included prior immune checkpoint inhibitor (ICI) treatment). Expansion cholangiocarcinoma IT and IV cohorts: one prior line of chemotherapy in metastatic/advanced setting. Patients with targetable tumor mutations must have also received 1 line of approved targeted therapy.
• Expansion cholangiocarcinoma IV cohort: prior treatment with leucovorin calcium, fluorouracil, or oxaliplatin is not permitted.
• ECOG performance status 0 - 2
• At least one measurable lesion
• For IT administration, ideally < 5 total lesions no greater than 10cm and <33% of liver volume replaced by tumor.
• Adequate renal function
• Adequate liver function
• Adequate hematologic function
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

• Prior treatment with a poxvirus based oncolytic virus.
• Continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment.
• Prior radiotherapy within 2 weeks of start of study treatment.
• Active autoimmune disease
• Prior allogenic tissue/organ transplant or other medical conditions requiring ongoing treatment with immunosuppressive drugs or any condition resulting in a systemic immunosuppressed state
• Inadequate pulmonary function per Investigator assessment.
• Uncontrolled brain or other central nervous system (CNS) metastases.
• History of documented congestive heart failure (New York Heart Association [NYHA] class III - IV), unstable angina, poorly controlled hypertension, clinically significant valvular heart disease or high-risk uncontrolled arrhythmias