A Phase 1/2a, First-In-Human, Single and Multiple Ascending Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of Intralesional FLD-103 in Subjects with Basal Cell Carcinoma (BCC)

Exclusion Criteria20

• Women of childbearing potential or who are breastfeeding.
• History of sensitivity to any of the components in the Investigational Product (IP) formulation.
• Target lesion in high-risk anatomic location (e.g. ocular/peri-ocular, nose/perinasal, ears, lips/perioral, scalp, fingers/hands).
• Target lesion requiring immediate surgical removal.
• Clinically confirmed concurrent diagnosis of locally advanced or metastatic BCC.
• Use of known inhibitors of the HH signalling pathway (including but not limited to vismodegib, sonidegib, itraconazole) within four (4) weeks of Screening.
• Use of topical or intralesional treatment within 5 cm of the target BCC (e.g. 5-FU, imiquimod, topical corticosteroids, retinoids) within the specified period
• Has received or is expected to receive phototherapy, including treatment with psoralen plus UVA or UVB therapy, within 4 weeks of the Screening visit or during the study.
• Use of another Investigational Product (IP) within thirty (30) days or five (5) halflives or twice the duration of biological effect (whichever is the longest) preceding the first dose of FLD-103.
• Subjects who have received radiation therapy to the target lesion and surrounding area (within 5 cm). Radiation to an unrelated body area is acceptable if done at least 30 days prior to Screening.
• A history of, or current hepatic disease, or known hepatic or biliary abnormalities that in the opinion of the Investigator would preclude the subject from participation in the study.
• Moderate to severe renal impairment, including subjects on chronic renal dialysis and subjects with a history of nephrectomy or kidney transplant (regardless of renal function)
• History of alcohol or drug abuse within the past 180 days, or a positive pre-study drug screen (unless the positive result is consistent with the use of a prescribed medication (e.g., codeine, benzodiazepines) or cannabinoids, as documented by the Investigator), or any current mental health condition (including, but not limited to, psychiatric disorder or dementia), that in the opinion of the Investigator, may interfere with study compliance, affect informed consent capacity, or impact the subject’s ability to follow the protocol and attend study visits.
• History or current evidence of any condition, laboratory abnormality or situation which, in the Investigator’s opinion, may put the subject’s safety at significant risk, confound the study results, interfere with the evaluation of the target lesion/treatment area or interfere with the subject’s participation in the study, (for example, but not limited to, other clinically active or uncontrolled skin disorders or tattoos that would interfere with evaluation of the area surrounding the target BCC, uncontrolled systemic disease such as metabolic dysfunction, clinically significant 12-lead ECG abnormalities, and any other physical examination findings, or abnormal clinical laboratory findings).
• Diagnosis of Xeroderma Pigmentosum or any other skin disorder that is associated with an abnormal rate of development of skin cancers or which may interfere with administration of the treatment and/or assessment of the target nBCC.
• History of any malignancy within the past five (5) years or has a known malignancy that is progressing or requires active treatment excluding BCC or non-metastatic squamous cell carcinoma, successfully treated melanoma stage 0 or 1, or in situ cervical cancer or prostate cancer, Gleason score 6 or lower.
• Immunocompromised (e.g. active Hepatitis A or B infection, current Hepatitis C infection, HIV infection) or receiving or expected to receive an immunomodulating agent (including immunosuppressive agents, cytotoxic drugs, biological agents, immunoglobulins, interferon or other immune or cytokine-based therapies. Use of oral corticosteroids at doses higher than physiological replacement doses (used in e.g. adrenal or pituitary insufficiency) is an exclusion criterion.
• Heart rate less than 40 or greater than 100 bpm; systolic blood pressure (SBP) greater than 140 mmHg; diastolic blood pressure (DBP) greater than 90 mmHg measured in up to three (3) separate intervals after resting for five (5) minutes in a supine or semi-recumbent position. Subjects with a history of hypertension are eligible if their condition is controlled and they have been on a stable dose of antihypertensive medications for at least four (4) weeks prior to Screening.
• Prolonged mean QTcF (QT interval corrected for heart rate using Fridericia’s formula) greater than 450 ms for male subjects or greater than 470 ms for female subjects, or a shortened QTcF less than 300 ms or a family history of prolonged QT syndrome, at Screening.
• Employee of the Investigator or study centre, with direct or indirect involvement in the proposed study or other studies under the direction of that Investigator or study centre, as well as family members of the employees or the Investigator.