Phase II Evaluation of Sonidegib in Nevoid Basal Cell Carcinoma Syndrome and Sporadic Basal Cell Carcinoma Patients in EADO Stage IIb

The primary objective of this phase II study is to evaluate **treatment compliance** in patients with Nevoid Basal Cell Carcinoma Syndrome (NBCCS) and sporadic Basal Cell Carcinoma (BCC) in EADO stage IIb. These patients will be treated with daily **sonidegib** for 16 weeks, followed by a pulsed dosing schedule for an additional 24 weeks. This objective is clinically relevant as it assesses the feasibility and adherence to a long-term treatment regimen, which is crucial for the management of chronic conditions like NBCCS and sporadic BCC.

Secondary objectives include: - Evaluating the **activity** of a pulsed sonidegib regimen after 16 weeks of daily administration. - Assessing the **efficacy** of the pulsed regimen in the same timeframe. - Determining the **safety** profile of the pulsed regimen. - Investigating the **impact on quality of life** for patients undergoing this treatment schedule.

The clinical trial involves participants diagnosed with **Nevoid Basal Cell Carcinoma Syndrome** or sporadic Basal Cell Carcinoma, specifically in EADO stage IIb. The study population includes both male and female subjects aged between 18 and 50 years. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The selection criteria include individuals who are difficult to treat and not amenable to surgery or radiotherapy, as evaluated by a multidisciplinary team. The trial population includes a vulnerable group, although specific lifestyle considerations such as diet or physical activity are not detailed in the available data.

The clinical trial is designed to evaluate the efficacy and safety of **sonidegib** in patients with Nevoid Basal Cell Carcinoma Syndrome (NBCCS) and sporadic Basal Cell Carcinoma (BCC) in EADO stage IIb. This is a phase II, randomized, double-blind, controlled study. The trial will involve a treatment period of 40 weeks, with an initial 16 weeks of daily dosing followed by a pulsed dosing schedule for the subsequent 24 weeks. The primary objective is to assess treatment compliance and the discontinuation rate due to adverse events (AEs), aiming for a rate of less than 54% at 40 weeks. Secondary endpoints include the overall response rate (ORR) according to RECIST criteria, progression-free survival (PFS) at 40 weeks, duration of response (DOR) of the pulsed regimen, and the rate of drug-related AEs.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and performance status. Follow-up visits will be scheduled throughout the treatment period to monitor safety, efficacy, and compliance. The end-of-study visit will occur at the conclusion of the 40-week treatment period. The expected length of participant involvement is approximately 40 weeks, with conditions for early termination including significant AEs or non-compliance with the study protocol. Participants must be between 18 and 50 years of age, have a confirmed diagnosis of NBCCS or sporadic BCC, and be deemed difficult to treat by a multidisciplinary team. The study will commence recruitment on January 23, 2025, with an estimated end date of June 30, 2027.

The clinical trial involves the administration of **Odomzo 200 mg hard capsules**, which contain the active substance **sonidegib**. This pharmaceutical form is classified as a hard capsule and is intended for oral administration. The maximum daily dose of sonidegib is 200 mg, with a total maximum dose of 39,200 mg over the course of the treatment. The treatment period is set for a maximum of 40 weeks. The trial protocol specifies an initial daily dosing schedule for 16 weeks, followed by a pulsed dosing schedule for the subsequent 24 weeks. The medication is manufactured by Sun Pharmaceutical Industries Europe B.V. and is authorized for use in the European Union under the marketing authorization number EU/1/15/1030/002.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of sonidegib to evaluate treatment compliance in patients with Nevoid Basal Cell Carcinoma Syndrome (Gorlin syndrome) and sporadic Basal Cell Carcinoma in EADO stage IIb. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment regimen. The trial aims to assess the efficacy and safety of sonidegib in the specified patient population.

Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the discontinuation rate of less than 54% due to adverse events (AEs) at 40 weeks from study entry in patients with Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or sporadic Basal Cell Carcinoma (BCC) in EADO stage IIb. These patients will be treated with daily **sonidegib** for 16 weeks, followed by a pulsed dosing schedule for the subsequent 24 weeks.

Secondary endpoints include the Objective Response Rate (ORR) according to RECIST criteria, Progression-Free Survival (PFS) at 40 weeks from study entry, and Duration of Response (DOR) of the pulsed sonidegib regimen. Additionally, the trial will evaluate the rate of any grade drug-related adverse events and Grade 3/4 drug-related adverse events of the pulsed sonidegib regimen. The EORTC QLQ C30 score will be measured at baseline, after 16 weeks of continuous daily sonidegib therapy, and after 24 weeks of the pulsed regimen to assess quality of life.