Basal Cell Carcinoma
Conditions
Brief summary
This is a multicenter, phase 2b, open-label, non-randomized, clinical trial to evaluate safety, tolerability, pharmacodynamics and preliminary efficacy of intra-lesional BO-112 in patients with resectable primary low and high risk basal cell carcinoma. * primary endpoint is composite visual and pathological response \[at surgery\] on patient level as assessed by central review * secondary endpoints are 1. Occurrence of adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation or death on patient level. 2. Pathological response \[at surgery\] on patient level assessed by the investigator and central review, respectively, and visual response \[during the study and at surgery\] on patient level assessed by the investigator and central review, respectively.
Detailed description
This study will be conducted in patients with resectable primary low- and high-risk basal cell carcinoma according to the following definition: Low-risk nodular BCC and/or low-risk superficial BCC: • Participants with primary resectable nodular and/or superficial BCC with well-defined borders with: * At least one lesion with the longest diameter from 5 to 10 mm located on cheeks, forehead, scalp, neck, and pretibial. OR * At least one lesion with the longest diameter from 5 to 20 mm located on trunk and extremities (excluding hands, feet, nail units, pretibial, and ankles). High-risk BCC: * Participants with primary resectable aggressive BCC (i.e. having morpheaform, basosquamous (metatypical), sclerosing, mixed infiltrative, or micronodular features in any portion of the lesion) with: * At least one lesion with the longest diameter from 5 mm to 30 mm in any body location. OR * Participants with primary resectable nodular and/or superficial BCC with * At least one lesion with the longest diameter from 5 mm to 30 mm located on central face, nose, lips, chin, mandible, preauricular and postauricular skin/sulci, temple, ear, genitalia, hands, and feet OR * At least one lesion larger than 10 mm to 30 mm located on cheeks, forehead, scalp, neck, and pretibial OR * At least one lesion larger than 20 mm to 30 mm located on trunk and extremities. For all participants: lesion(s) intended to be injected must be at least 2 cm apart from the open eyelid margins. Participants with multiple lesions in both groups must have a diagnostic punch or incisional biopsy from all lesions intended for injection and all lesions intended for injection must be resectable and injectable.
Interventions
DRUGBO-112
Noncoding double-stranded (ds) RNA based on polyinosinic-polycytidylic acid (Poly I:C), formulated with polyethylenimine (PEI) for intra-lesional injection
Sponsors
Highlight Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel group design with same treatment and study procedures
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant must be ≥ 18 years old \[or the legal age of consent in the jurisdiction in which the study is taking place\], at the time of signing the informed consent. Type of Participant and Disease Condition 2. Has primary resectable low or high risk basal cell carcinoma according to the protocol definition 3. Has diagnostic punch biopsy of all lesions intended for injection available prior to the first dose of BO-112. 4. Has adequate laboratory values as defined per protocol Sex and Contraceptive/Barrier Requirements 5. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of study drug. 6. Women of childbearing potential must be willing to use two effective methods of birth control while treated with BO-112 and for 4 weeks after the last treatment. The two forms of birth control authorized are defined as the use of a barrier method of contraception (condom with spermicide) in association with one of the following methods of birth control: bilateral tubal ligation; combined oral contraceptives (estrogens and progesterone) or implanted or injectable contraceptives from the time of informed consent. 7. Male patients with female partners of childbearing potential must be willing to use two adequate contraception methods while treated with BO-112 and for 4 weeks after treatment completion. Informed Consent 8. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 9. Able and willing to comply with all study requirements, including surgical removal of lesion/lesion site at completion of study.
Exclusion criteria
1. Has history of hypersensitivity to BO-112 or its excipients/vehicle. 2. Has any BCC lesion(s) planned for injection in site of prior radiation within 6 months prior to first dose of BO-112. 3. Has any BCC lesion(s) planned for injection within 2 cm of the open eyelid margins 4. Has Gorlin's syndrome 5. Has clinically active or uncontrolled skin disease or tattoos that would interfere with evaluation of the area surrounding the target lesion 6. Has another malignant disease requiring treatment 7. Has a history of immunological disorder, severe allergic reaction, moderate or severe asthma or known history of anaphylaxis or any other serious adverse reactions to the investigational products. 8. Female participants: lactating or pregnant. 9. Has received a live vaccine or messenger ribonucleic acid (mRNA) Corona virus disease (COVID) vaccine within 7 days prior to the first dose of study drug or has a vaccination planned during treatment with BO-112 and within 7 days after the last study drug administration. 10. Is immunocompromised. Systemic corticosteroids at \>10 mg/day prednisone or equivalent within 1 week prior to the first dose of BO-112. 11. Has any prior systemic anti-lesion therapy or local treatment for study lesions prior to first dose; any chemotherapy or immunotherapy for any other malignancy within 24 months prior to the first dose of BO-112. 12. Has any experimental or investigational agents within one month of first BO-112 injection. 13. Has received or is expected to receive treatment with psoralen plus ultraviolet A (UVA) or ultraviolet B (UVB) therapy within 6 months prior to the first dose of BO-112. 14. Requires / or has used topical products within 5 cm of a treatment-targeted BCC lesion or systemic therapies that might interfere with the evaluation of the study medication during the study. 15. Has any other concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational \[used for a not approved indication and in the context of a research investigation\]) within 28 days of first study drug administration; or plans to participate in an experimental drug study while enrolled in this study. 16. Has any medical contraindications to surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Visual and Pathological Response | at surgery | The composite primary endpoint of the visual and pathological response is defined as visual and pathological response on patient level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment-Related Adverse Events assessed by CTCAE 5.0 | through study completion, average 7 months | Occurrence of adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation or death on participant level. |
| Extent of Pathological Response | at surgery | Pathological response on participant level assessed by the investigator and central review, respectively, using a 4-point scale 1. Pathologic Complete Response (pCR): No Residual Viable Tumor (RVT) 2. Major Pathologic Response (MPR)/ "near-pCR": \<= 10% RVT 3. Pathologic Partial Response (pPR): 10% \< RVT \<= 50% " 4. Pathologic Non-Response" (pNR): \>50% RVT |
| Change of Visual Lesion Appearance | at baseline and at surgery | Visual response \[during the study and at surgery\] on participant level assessed by the investigator and central review, respectively. |
Countries
Israel, Spain
Outcome results
None listed