Basal Cell Carcinoma
Conditions
Keywords
locally advanced basal cell carcinoma, metastatic basal cell carcinoma, LDE225, sonidegib, Basel Cell Carcinoma (BCC), skin cancer, Basel Cell Carcinoma, BCC
Brief summary
This study assessed the efficacy and safety of oral treatment with two dose levels of LDE225 in patients with locally advanced or metastatic BCC.
Interventions
DRUGLDE225
LDE225 was administered orally, on a continuous once daily dosing schedule and was supplied as 200 mg hard gelatin capsules in bottles. Every 4 weeks on the day of study visit, patients received a prescription of an adequate drug supply for self-administration at home. The 800 mg dose patients received 4 capsules of LDE225 and 200 mg dose arm patients received 1 LDE225 capsule + 3 placebo capsules.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with locally advanced BCC and metastatic BCC * Patients with adequate bone marrow, liver, and renal function
Exclusion criteria
* Patients who had had major surgery within 4 weeks of initiation of study medication * Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract, or known malabsorption syndromes. * Patients with concurrent medical conditions that may interfere or potentially affect the interpretation of the study. * Patients with neuromuscular disorders or are on concurrent treatment with drugs that may cause muscle damage. * Patients who were on concurrent therapy with other anti-neoplastic agents. * Patients who had taken part in an experimental drug within 4 weeks of initiation of study medication. * Pregnant or nursing (lactating) women * Women of child bearing potential unwilling to use 2 forms of highly effective contraception throughout the study and for 3 months after the last treatment * Fertile males not willing to use condoms throughout the study and for 3 months after the last treatment. * Patients who were unwilling or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 6 months | ORR is the percentage of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 6 months after starting LDE225 treatment.Treatment with sonidegib was considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 6 months | ORR is the percentage of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 6 months after starting LDE225 treatment.Treatment with sonidegib was to be considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) Per Central Review (pEAS) | 42 months | Rate of complete response is the percentage of patients with best overall response of complete response (CR) after starting LDE225 treatment. The rate of CR was determined according to mRECIST for laBCC and RECIST 1.1 for mBCC. Patients with best overall response of 'Unknown were treated as non responders. Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Complete Response Rate (CRR) Per Central Review (FAS) | 6 months | Rate of complete response is the proportion of patients with best overall response of complete response (CR) after starting LDE225 treatment. The rate of CR will be determined according to mRECIST for laBCC and RECIST 1.1 for mBCC. Patients with best overall response of 'Unknown will be treated as non responders |
| Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 42 months | Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. |
| Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 42 months | Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment. |
| Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 42 months | Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 42 months | Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 42 months | ORR is the percentage of patient's objective response (ORR) by 42 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 42 months after starting LDE225 treatment. Treatment with sonidegib was considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 42 months | Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Progressive disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. |
| Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 42 months | Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Progressive disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. |
| Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 42 months | Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 42 months | Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. |
| Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 42 months | Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Plasma Concentration of Sonidegib (LDE225) | Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69 | Blood PK samples were collected either by direct venipuncture or an indwelling cannula inserted in a forearm vein for the determination of trough (Cmin) plasma concentrations of sonidegib and its main circulating metabolite, LGE899, from all patients who enrolled in the study. Blood was collected in Weeks 1, 3, 5, 9 (pre-dose), and subsequently pre-dose every 4 weeks up to Week 21, and every 12 weeks thereafter up to week 69. |
| Overall Survival (OS) | 42 months | OS is defined as the time from date of randomization to date of death due to any cause or the last date that a patient was known to be alive (censored observation) as of the data cut-off. |
| Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 42 months | ORR is the percentage of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 42 months after starting LDE225 treatment.Treatment with sonidegib was to be considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
| Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 42 months | Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Median DoR for patients with laBCC was non-estimable for both treatment arms. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. |
Countries
Australia, Belgium, Canada, France, Germany, Greece, Hungary, Italy, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Randomization was stratified across the two treatment arms according to the stage of disease (laBCC or mBCC), histological subtype (non-aggressive or aggressive for laBCC patients) and the regions (Australia, Europe, and North America).
Pre-assignment details
All eligible, enrolled patients were randomized in 1:2 ratio to sonidegib treatment with either 200 mg or 800 mg once-daily dose. In total, 230 patients were evaluated as FAS population: 79 and 151 patients randomized to 200mg and 800 mg sonidegib respectively. However, 1 patient randomized to 800 mg sonidegib did not receive study treatment.
Participants by arm
| Arm | Count |
|---|---|
| LDE225 (Sonidegib) 200 mg The study is double blinded and will enroll at least 50 evaluable patients in the 200 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be treated with 200 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent. | 79 |
| LDE225 (Sonidegib) 800 mg The study is double blinded and will enroll at least 100 evaluable patients in the 800 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be treated with 800 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent. | 151 |
| Total | 230 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 23 | 57 |
| Overall Study | Death | 1 | 5 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Non-compliance with study treatment | 0 | 5 |
| Overall Study | Patient/guardian decision | 11 | 35 |
| Overall Study | Physician Decision | 10 | 14 |
| Overall Study | Progressive disease | 31 | 26 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Study terminated by Sponsor | 1 | 3 |
| Overall Study | Untreated | 0 | 1 |
Baseline characteristics
| Characteristic | LDE225 (Sonidegib) 200 mg | LDE225 (Sonidegib) 800 mg | Total |
|---|---|---|---|
| Age, Continuous | 65.6 Years STANDARD_DEVIATION 15.67 | 63.6 Years STANDARD_DEVIATION 14.59 | 64.3 Years STANDARD_DEVIATION 14.96 |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 71 Participants | 145 Participants | 216 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Female | 31 Participants | 55 Participants | 86 Participants |
| Sex: Female, Male Male | 48 Participants | 96 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 79 | 7 / 150 |
| other Total, other adverse events | 76 / 79 | 145 / 150 |
| serious Total, serious adverse events | 16 / 79 | 58 / 150 |
Outcome results
Primary
Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS)
ORR is the percentage of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 6 months after starting LDE225 treatment.Treatment with sonidegib was considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 6 months
Population: The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, \& including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDE225 200mg laBCC | Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 42.9 Percentage of participants |
| LDE225 800mg laBCC | Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 37.6 Percentage of participants |
| LDE225 200mg mBCC | Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 15.4 Percentage of participants |
| LDE225 800mg mBCC | Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 17.4 Percentage of participants |
Primary
Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS)
ORR is the percentage of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 6 months after starting LDE225 treatment.Treatment with sonidegib was to be considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 6 months
Population: The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDE225 200mg laBCC | Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 47.0 Percentage of participants |
| LDE225 800mg laBCC | Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 35.2 Percentage of participants |
| LDE225 200mg mBCC | Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 15.4 Percentage of participants |
| LDE225 800mg mBCC | Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 17.4 Percentage of participants |
Secondary
Complete Response Rate (CRR) Per Central Review (FAS)
Rate of complete response is the proportion of patients with best overall response of complete response (CR) after starting LDE225 treatment. The rate of CR will be determined according to mRECIST for laBCC and RECIST 1.1 for mBCC. Patients with best overall response of 'Unknown will be treated as non responders
Time frame: 6 months
Population: The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients). Patients were classified according to the treatment they were assigned in accordance with the intention-to-treat (ITT) principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDE225 200mg laBCC | Complete Response Rate (CRR) Per Central Review (FAS) | 3.0 Percentage of participants |
| LDE225 800mg laBCC | Complete Response Rate (CRR) Per Central Review (FAS) | 0.0 Percentage of participants |
| LDE225 200mg mBCC | Complete Response Rate (CRR) Per Central Review (FAS) | 0.0 Percentage of participants |
| LDE225 800mg mBCC | Complete Response Rate (CRR) Per Central Review (FAS) | 0.0 Percentage of participants |
Secondary
Complete Response Rate (CRR) Per Central Review (pEAS)
Rate of complete response is the percentage of patients with best overall response of complete response (CR) after starting LDE225 treatment. The rate of CR was determined according to mRECIST for laBCC and RECIST 1.1 for mBCC. Patients with best overall response of 'Unknown were treated as non responders. Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 42 months
Population: The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, \& including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDE225 200mg laBCC | Complete Response Rate (CRR) Per Central Review (pEAS) | 4.8 Percentage of participants |
| LDE225 800mg laBCC | Complete Response Rate (CRR) Per Central Review (pEAS) | 2.2 Percentage of participants |
| LDE225 200mg mBCC | Complete Response Rate (CRR) Per Central Review (pEAS) | 0.0 Percentage of participants |
| LDE225 800mg mBCC | Complete Response Rate (CRR) Per Central Review (pEAS) | 0.0 Percentage of participants |
Secondary
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Median DoR for patients with laBCC was non-estimable for both treatment arms. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 42 months
Population: The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients). Patients were classified according to the treatment they were assigned in accordance with the intention-to-treat (ITT) principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 26.1 Months |
| LDE225 800mg laBCC | Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 23.3 Months |
| LDE225 200mg mBCC | Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 24.0 Months |
| LDE225 800mg mBCC | Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | NA Months |
Secondary
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Progressive disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
Time frame: 42 months
Population: The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, \& including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 12.9 Months |
| LDE225 800mg laBCC | Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 23.7 Months |
| LDE225 200mg mBCC | Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 24.0 Months |
| LDE225 800mg mBCC | Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | NA Months |
Secondary
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 42 months
Population: The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients). Patients were classified according to the treatment they were assigned in accordance with the intention-to-treat (ITT) principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 15.7 Months |
| LDE225 800mg laBCC | Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 26.0 Months |
| LDE225 200mg mBCC | Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 18.1 Months |
| LDE225 800mg mBCC | Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 10.2 Months |
Secondary
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Progressive disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
Time frame: 42 months
Population: The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, \& including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 18.2 Months |
| LDE225 800mg laBCC | Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 26.0 Months |
| LDE225 200mg mBCC | Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 18.1 Months |
| LDE225 800mg mBCC | Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 10.2 Months |
Secondary
Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS)
ORR is the percentage of patient's objective response (ORR) by 42 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 42 months after starting LDE225 treatment. Treatment with sonidegib was considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 42 months
Population: The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, \& including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDE225 200mg laBCC | Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 71.4 Percentage of participants |
| LDE225 800mg laBCC | Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 61.3 Percentage of participants |
| LDE225 200mg mBCC | Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 23.1 Percentage of participants |
| LDE225 800mg mBCC | Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) | 34.8 Percentage of participants |
Secondary
Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS)
ORR is the percentage of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 42 months after starting LDE225 treatment.Treatment with sonidegib was to be considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 42 months
Population: The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDE225 200mg laBCC | Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 71.2 Percentage of participants |
| LDE225 800mg laBCC | Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 58.6 Percentage of participants |
| LDE225 200mg mBCC | Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 23.1 Percentage of participants |
| LDE225 800mg mBCC | Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) | 34.8 Percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as the time from date of randomization to date of death due to any cause or the last date that a patient was known to be alive (censored observation) as of the data cut-off.
Time frame: 42 months
Population: The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients). Patients were classified according to the treatment they were assigned in accordance with the intention-to-treat (ITT) principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Overall Survival (OS) | NA Months |
| LDE225 800mg laBCC | Overall Survival (OS) | NA Months |
| LDE225 200mg mBCC | Overall Survival (OS) | 47.6 Months |
| LDE225 800mg mBCC | Overall Survival (OS) | 33.8 Months |
Secondary
Plasma Concentration of Sonidegib (LDE225)
Blood PK samples were collected either by direct venipuncture or an indwelling cannula inserted in a forearm vein for the determination of trough (Cmin) plasma concentrations of sonidegib and its main circulating metabolite, LGE899, from all patients who enrolled in the study. Blood was collected in Weeks 1, 3, 5, 9 (pre-dose), and subsequently pre-dose every 4 weeks up to Week 21, and every 12 weeks thereafter up to week 69.
Time frame: Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
Population: The PK analysis set (PAS) consisted of all patients with at least one evaluable plasma concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 13 (0 h (pre-dose)) | 714.01 ng/mL | Geometric Coefficient of Variation 60.79 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (4 h (post-dose)) | 842.31 ng/mL | Geometric Coefficient of Variation 62.22 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 3 (0 h (pre-dose)) | 207.76 ng/mL | Geometric Coefficient of Variation 78.29 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (6 h (post-dose)) | 759.88 ng/mL | Geometric Coefficient of Variation 63.43 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (0 h (pre-dose)) | 688.93 ng/mL | Geometric Coefficient of Variation 64.43 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 21 (0 h (pre-dose)) | 707.49 ng/mL | Geometric Coefficient of Variation 63.58 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 9 (0 h (pre-dose)) | 559.29 ng/mL | Geometric Coefficient of Variation 67.3 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 33 (0 h (pre-dose)) | 702.67 ng/mL | Geometric Coefficient of Variation 93.11 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (1 h (post-dose)) | 841.78 ng/mL | Geometric Coefficient of Variation 52.57 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 45 (0 h (pre-dose)) | 697.92 ng/mL | Geometric Coefficient of Variation 76.02 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 5 (0 h (pre-dose)) | 372.26 ng/mL | Geometric Coefficient of Variation 68.89 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 57 (0 h (pre-dose)) | 559.17 ng/mL | Geometric Coefficient of Variation 117.27 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (2 h (post-dose)) | 939.56 ng/mL | Geometric Coefficient of Variation 50.79 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Wek 69 (0 h (pre-dose)) | 530.91 ng/mL | Geometric Coefficient of Variation 154.33 |
| LDE225 200mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 1 (0 h (pre-dose)) | NA ng/mL | — |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Wek 69 (0 h (pre-dose)) | 1355.91 ng/mL | Geometric Coefficient of Variation 89.03 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 1 (0 h (pre-dose)) | NA ng/mL | — |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 3 (0 h (pre-dose)) | 586.76 ng/mL | Geometric Coefficient of Variation 97.13 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 5 (0 h (pre-dose)) | 1012.63 ng/mL | Geometric Coefficient of Variation 70.42 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 9 (0 h (pre-dose)) | 1353.06 ng/mL | Geometric Coefficient of Variation 63.43 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 13 (0 h (pre-dose)) | 1443.84 ng/mL | Geometric Coefficient of Variation 61.57 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (0 h (pre-dose)) | 1574.21 ng/mL | Geometric Coefficient of Variation 59.88 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (1 h (post-dose)) | 1803.74 ng/mL | Geometric Coefficient of Variation 39.47 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (2 h (post-dose)) | 1922.38 ng/mL | Geometric Coefficient of Variation 34.9 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (4 h (post-dose)) | 1750.70 ng/mL | Geometric Coefficient of Variation 53.32 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 17 (6 h (post-dose)) | 1673.95 ng/mL | Geometric Coefficient of Variation 41.53 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 21 (0 h (pre-dose)) | 1547.41 ng/mL | Geometric Coefficient of Variation 63.92 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 33 (0 h (pre-dose)) | 1477.60 ng/mL | Geometric Coefficient of Variation 74.8 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 45 (0 h (pre-dose)) | 1368.87 ng/mL | Geometric Coefficient of Variation 79.6 |
| LDE225 800mg laBCC | Plasma Concentration of Sonidegib (LDE225) | Week 57 (0 h (pre-dose)) | 1257.42 ng/mL | Geometric Coefficient of Variation 78.96 |
Secondary
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
Time frame: 42 months
Population: The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 22.1 Months |
| LDE225 800mg laBCC | Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 24.9 Months |
| LDE225 200mg mBCC | Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 13.1 Months |
| LDE225 800mg mBCC | Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 11.1 Months |
Secondary
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
Time frame: 42 months
Population: The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, \& including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 19.0 Months |
| LDE225 800mg laBCC | Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 19.4 Months |
| LDE225 200mg mBCC | Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 13.1 Months |
| LDE225 800mg mBCC | Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 11.1 Months |
Secondary
Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
Time frame: 42 months
Population: The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, \& including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 20.1 Months |
| LDE225 800mg laBCC | Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 28.0 Months |
| LDE225 200mg mBCC | Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 13.1 Months |
| LDE225 800mg mBCC | Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 14.3 Months |
Secondary
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 42 months
Population: The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 4.0 Months |
| LDE225 800mg laBCC | Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 3.7 Months |
| LDE225 200mg mBCC | Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 9.2 Months |
| LDE225 800mg mBCC | Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) | 1.0 Months |
Secondary
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 42 months
Population: The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, \& including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 4.0 Months |
| LDE225 800mg laBCC | Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 3.7 Months |
| LDE225 200mg mBCC | Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 9.2 Months |
| LDE225 800mg mBCC | Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 1.0 Months |
Secondary
Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.
Time frame: 42 months
Population: The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, \& including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDE225 200mg laBCC | Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 1.9 Months |
| LDE225 800mg laBCC | Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 1.8 Months |
| LDE225 200mg mBCC | Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 1.0 Months |
| LDE225 800mg mBCC | Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) | 2.7 Months |