Intralesional BO-112 in patients with resectable basal cell carcinoma: results from the phase 2b SPOTLIGHT-204 trial

Introduction: Basal cell carcinoma (BCC) is the most common human malignancy and its incidence continues to rise globally. Mohs micrographic and conventional surgery achieve high cure rates in both high- and low-risk BCC, however, can result in significant scarring and functional compromise, particularly on the head and neck (H&N). Effective non-surgical options in dermatology practice remain an unmet clinical need. BO-112 is a dsRNA immunotherapy designed to activate an innate and adaptive immune response and immunogenic tumour-cell death. Methods: SPOTLIGHT-204 is a multi-centre, phase 2b, single-arm, two-cohort clinical trial evaluating efficacy, safety and tolerability of intralesional BO-112 injection in 50 patients (40 high-risk (HR), 10 low-risk (LR)) with resectable, histologically confirmed, HR and LR BCC lesions. Patients received three once weekly intralesional injections followed by protocol-mandated complete surgical excision between week 24 and 30. Visual and pathological responses were evaluated by a Central Review Committee. Visual efficacy was Grade: 1) complete (complete lesion disappearance or scar); 2) partial (≥30% reduction in lesion size); 3) no change / smaller than partial; or 4) lesion growth (≥20% increase in lesion size). Pathological response, at the time of surgical excision, was Grade: 1) complete (no residual viable tumour (RVT); 2) major (≤10% RVT); 3) partial (>10% ≤50% RVT); or 4) no response (>50% RVT). We report results in a 46-patient modified intention to treat population with 54 evaluable lesions. Results: The median age was 75.0 years (range 34–90). 22 (48%) were female and 24 (52%) male. Lesions were located on the face (33, 61%); H&N (6, 11%); extremities (8, 15%); trunk (7, 13%). Lesion median longest diameter was 12 mm (range 6–34 mm). Mean BO-112 cumulative exposure was 1.25 mg. The composite primary endpoint was defined as both visual and pathological response of Grade 3 or better in all treated lesions at patient level. This was demonstrated in 28 (61%) of patients, with high concordance between visual and histological assessments. In patients with HR lesions, this was 58% (n=21) and 70% (n=7) with LR lesions. Complete and major pathological responses were observed in: 20 (56%) of HR patients and 5 (50%) of LR patients. In the H&N patients 56% achieved complete pathological response with high concordance between visual and histological assessments. BO-112 was well tolerated: 91% of BO-112-related adverse events were grade 1, transient, flu-like or injection-site reactions; none were grade ≥3 and none were serious. Conclusion: Intralesional BO-112 achieved high rates of composite visual and pathological response in both LR and HR patients, with even larger benefits in the highest unmet need group of HR-H&N patients, with a manageable and predominantly low-grade safety profile. These results support further development of BO-112 as a non-surgical option that addresses a meaningful unmet need in BCC treatment. This study was sponsored by Highlight Therapeutics SA, Spain