Inclusion
1. At least 18 years of age and up to 85 years of age, inclusive, at the time of signing the informed consent.
2. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and is willing and able to return for all study visits and comply with all protocol requirements and procedures.
3. At Screening, the subject must have at least a single histologically confirmed nBCC suitable for treatment and final excision by the Investigator.
4. A nBCC previously biopsied outside the study as part of standard clinical practice may be re-biopsied within the study, provided that less than approximately 25 percent of the area of the nodular lesion is removed as a result of the second biopsy.
5. If no previous biopsy is available, target nBCC must be appropriate for a full thickness 2 mm punch biopsy (for lesions from 5 mm up to less than 10 mm diameter) or preferrably a 3 mm punch biopsy (for lesions from 10 mm to less than 20 mm diameter), taken approximately halfway from the centre or outer border of each target nBCC, within 14 to 42 days prior to Day 1 for histological confirmation at Baseline. The biopsy(ies) must remove less than approximately 25 percent of the area of the nBCC.
6. Target BCC must, in the assessment of the Investigator, be appropriate for FLD-103 intralesional treatment over the anticipated duration of the study.
7. Female volunteers, must:
a. Be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit, or
b. Be postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines).
8. Male volunteers, must:
a. Agree not to donate sperm from signing the consent form until at least 90 days after the last dose of study drug.
b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception from signing the consent form until at least 90 days after the last dose of study drug.
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 90 days after the last dose of study drug.
Exclusion
1. Women of childbearing potential or who are breastfeeding.
2. History of sensitivity to any of the components in the Investigational Product (IP) formulation.
3. Target lesion in high-risk anatomic location (e.g. ocular/peri-ocular, nose/perinasal, ears, lips/perioral, scalp, fingers/hands).
4. Target lesion requiring immediate surgical removal.
5. Clinically confirmed concurrent diagnosis of locally advanced or metastatic BCC.
6. Use of known inhibitors of the HH signalling pathway (including but not limited to vismodegib, sonidegib, itraconazole) within four (4) weeks of Screening.
7. 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
8. 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.
9. 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.
10. 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.
11. 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.
12. 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)
13. 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.
14. 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).
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.