Trial Outcomes & Findings for Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients (NCT NCT02762084)

Weight data at baseline was not available for 1 participant in the Patidegib Gel 4% treatment arm.

SEBs were defined as clinically diagnosed basal cell carcinoma (BCC) 5 millimeters (mm) or greater in diameter on the face, excluding the nose and periorbital skin, and 9 mm or greater at sites other than the face. The percent change in greatest diameters of treatment-targeted surgically eligible basal cell carcinomas (SEBs) from Baseline to Week 26 was calculated as follows: (sum \[Baseline\] - sum \[Week 26\] / sum \[Baseline\] \* 100), where sum = the greatest diameters of Baseline treatment-targeted SEBs and positive numbers represent decrease in tumor size and negative numbers to represent increase in tumor size. Missing values were imputed using Last-Observation Carried Forward (LOCF).

SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin, and 9-mm or greater at sites other than the face. A single baseline SEB designated as a treatment targeted tumor at Baseline was biopsied first at Baseline and again following 6 weeks of treatment. This was used to assess percent change in GLI1 mRNA levels as follows: (Baseline - Week 6) / Baseline \* 100, where positive numbers to represent decrease in GL1 mRNA level and negative numbers to represent increase in GL1 mRNA level. Any missing values were not imputed; all available data is summarized.

All serious adverse events (SAEs) and all other non-serious adverse events (AEs) regardless of causality are located in the Reported AE Module. AEs considered as related where categorized by the Investigator as either definitely related, probably related, or possibly related. Treatment-emergent AEs are those with an onset after use of study drug.

All SAEs and all other non-serious AEs, regardless of causality, are located in the Reported AE Module. The number of participants reporting administrative-site, skin condition treatment-emergent AEs considered related to study drug by the Investigator are presented below. Treatment-emergent AEs are those with an onset after use of study drug.

Facial SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin. A new facial SEB was defined as an SEB first noted on the face after Week 2 that developed at a site where there was no visible BCC of any size at Baseline or Week 2. New facial SEBs were investigated for participants on vehicle gel versus participants on patidegib 2% and 4% gel. Missing values were imputed using LOCF.

Facial SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin. A new facial SEB was defined as an SEB first noted on the face after Week 2 that developed at a site where there was no visible BCC of any size at Baseline or Week 2. New facial SEBs were investigated for participants on vehicle gel versus participants on patidegib 2% and 4% gel. Missing values were imputed using LOCF. The mean number of new SEBs (number per participant) are presented. No measure of dispersion/precision was calculated.

Facial SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin. A new facial SEB was defined as an SEB first noted on the face after Week 2 that developed at a site where there was no visible BCC of any size at Baseline or Week 2. New facial SEBs were investigated for participants on vehicle gel versus participants on patidegib 2% and 4% gel. Missing values were imputed using LOCF. The mean number of new SEBs (number per participant) are presented. No measure of dispersion/precision was calculated.

SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin, and 9 mm or greater at sites other than the face. The percent change in greatest diameters of Baseline treatment-targeted SEBs from Baseline to Week x (Week 6, 10, 14, 18, or 22) was calculated as follows: (sum \[Baseline\] - sum \[Week x\] / sum \[Baseline\] \* 100), where sum = the greatest diameters of Baseline treatment-targeted SEBs, and positive numbers to represent decrease in tumor size and negative numbers to represent increase in tumor size. Missing values were imputed using LOCF.

Central facial SEBs were defined as those located on the nose or periorbital area (eyelids) which were 3 mm or greater at Baseline. The percent change from Baseline to Week x (Week x = Weeks 6, 10, 14, 18, 22, or 26) in central facial SEBs was calculated as follows: \[sum (Baseline) - sum (Week x)\] / \[sum (Baseline)\] \* 100 where sum = the greatest diameters of Baseline treatment-targeted SEBs where positive numbers to represent decrease in tumor size and negative numbers to represent increase in tumor size. Missing values were imputed using LOCF.

The proportion of non-central facial BCCs that at Baseline measured a greatest diameter of \< 5 mm and increased to a diameter of ≥ 5 mm by Week x (Week x = Weeks 6, 10, 14, 18, 22, or 26) were calculated for each participant as follows: (Number of non-central facial BCCs with greatest diameter ≥ 5 mm at Week x) / (Number of non-central facial BCCs with greatest diameter \< 5 mm at Baseline). Missing values were imputed using LOCF.

SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin, and 9 mm or greater at sites other than the face. The proportion of Baseline treatment-targeted SEBs that at the end of 26 weeks of treatment were no longer large enough to be classified as SEBs (that is, the proportion of Baseline treatment targeted SEBs on the face that became \< 5 mm in greatest diameter and non-facial Baseline treatment targeted SEBs that became \< 9 mm in greatest diameter) were calculated for each participant as follows: (Number of Baseline treatment-targeted facial SEBs with greatest diameter \< 5 mm) + (Baseline treatment targeted non-facial SEBs with greatest diameter \< 9 mm) / Number of baseline treatment targeted SEBs. Missing values were imputed using LOCF.

The ISGTA is a scale with scores ranging from 0 (clear), 1 (almost clear), 2 (minimal residual tumor), to 3 (clearly visible tumor). The Investigator assessed each Baseline treatment-targeted SEB at Weeks 6, 10, 14, 18, 22, and 26. SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin, and 9 mm or greater at sites other than the face. The percentage of Baseline treatment-targeted SEBs evaluated as being clear or almost clear at Week x (Week x = Week 6, 10, 14, 18, 22 or 26) based on the ISGTA scale was calculated as follows: (Number of baseline treatment-targeted SEBs with ISGTA score of 0 or 1 at Week x) / (Number of Baseline treatment-targeted SEBs) \* 100. Missing data were imputed using LOCF. The percentage of responders achieving clear (0) or almost clear (1) on the ISGTA scale are presented by Week.