Triple Negative Breast Neoplasms
Conditions
Keywords
Triple Negative Breast Cancer, alpelisib, BYL719, nab-paclitaxel, PIK3CA mutation, PTEN loss
Brief summary
The purpose of this study was to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with advanced triple negative breast cancer (aTNBC) who carry either a PIK3CA mutation (Study Part A) or have PTEN loss (Study Part B1) or PTEN loss without PIK3CA mutation (Study Part B2)
Detailed description
The recruitment of Part A was halted on 11-Nov-2022 due to slow recruitment. Since Part B1 did not meet its primary objective for confirmed overall response rate, the Part B2 was not initiated, and the recruitment was halted for the entire study. Upon confirming either PIK3CA mutation and/or PTEN loss status, advanced TNBC participants meeting all other eligibility criteria were assigned to either Part A (PIK3CA mutation regardless of PTEN loss) or Part B1 (PTEN loss with PIK3CA unknown or non-mutant). In Part A, participants were randomized a 1:1 to receive either: * alpelisib 300 mg daily orally + nab-paclitaxel 100 mg/m\^2 intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle or * placebo + nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle. In Part B1, participants received alpelisib 300 mg daily orally + nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle.
Interventions
DRUGalpelisib
300 mg orally, once per day (QD), tablets
DRUGplacebo
300 mg orally, once per day (QD), tablets
DRUGnab-paclitaxel
100 mg/m\^2 IV infusion, once per day (QD)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Participant has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy), or metastatic (stage IV) TNBC * Participant has either a measurable disease per RECIST 1.1 criteria or, if no measurable disease is present, then at least one predominantly lytic bone lesion or mixed lytic-blastic bone lesion with identifiable soft tissue component (that can be evaluated by CT/MRI) must be present. Part B1: Participants must have measurable disease * Participant has adequate tumor tissue to identify the PIK3CA mutation status (either carrying a mutation or without a mutation) and the PTEN loss status; both of which will determine whether the subject can be allocated to Part A - PIK3CA mutation regardless of PTEN status; or to Part B1 - PTEN loss or to Part B2 - PTEN loss without a PIK3CA mutation * Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Participant has received no more than one line of therapy for metastatic disease * Participant has adequate bone marrow and organ function
Exclusion criteria
* Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor * Participant has a known hypersensitivity to alpelisib, nab-paclitaxel or to any of their excipients * Participant has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1; with the exception of alopecia * Participant has central nervous system (CNS) involvement which was not previously treated and/or was newly detected at screening * Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on Fasting Plasma Glucose and HbA1c * Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) based on investigator discretion * Participant has a history of acute pancreatitis within 1 year prior to screening or past medical history of chronic pancreatitis * Participant has currently documented pneumonitis/interstitial lung disease * Participant has a history of severe cutaneous reactions, such as Steven-Johnson Syndrome (SJS), erythema multiforme (EM),Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Syndrome (DRESS) * Participant with unresolved osteonecrosis of the jaw
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Per Investigator Assessment in Study Part A | Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months | PFS was defined as time from the date of randomization to the date of the first documented progressive disease (PD) or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. 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 mm\^2. PFS was censored at the date of the last adequate tumor assessment, if no PFS event was observed prior to the analysis cut-off date. |
| Overall Response Rate (ORR) Based on Local Radiology Assessments in Participants With Measurable Disease at Baseline in Study Part B1 | Up to 6 months | ORR was defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. BOR was defined as the best response recorded from the start of the study treatment until progressive disease (PD)/recurrence. 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. PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; PD= At least a 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in Study Part A | Up to 66 months | Overall survival is defined as the time from date of randomization to date of death due to any cause. |
| Overall Response Rate (ORR) With Confirmed Response in Study Part A | Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months | ORR with confirmed response was the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as per local review and according to RECIST 1.1. BOR was defined as the best response recorded from the start of the study treatment until progressive disease (PD)/recurrence. 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. PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; PD= At least a 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Clinical Benefit Rate (CBR) With Confirmed Response in Study Part A | Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months | Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1 based on investigator's assessment. 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 PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease. |
| Clinical Benefit Rate (CBR) With Confirmed Response in Study Part B1 | Up to 6 months | Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1 based on investigator's assessment. 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 PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease. |
| Time to Response (TTR) in Study Part A | Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months | Time to response (TTR) was defined as the time from the date of randomization/enrolment to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed (although date of initial response is used, not date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1. 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; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Time to Response (TTR) in Study Part B1 | Up to 6 months | Time to response (TTR) was defined as the time from the date of randomization/enrolment to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed (although date of initial response was used, not date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1. 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; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Duration of Response (DOR) With Confirmed Response in Study Part A | Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months | Duration of response (DOR) with confirmed response only applied to participants whose best overall response (BOR) was confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progressive disease (PD) or death due to underlying cancer. 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; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Duration of Response (DOR) With Confirmed Response in Study Part B1 | Up to approximately 20 months | Duration of response (DOR) with confirmed response only applied to participants whose best overall response (BOR) was confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progressive disease (PD) or death due to underlying cancer. 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; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Overall Survival in Study Part B1 | Up to approximately 26 months. | Overall survival for Part B1 was defined as the number of participants who were alive at the end of the post-treatment period. |
| Progression-free Survival (PFS) Per Investigator Assessment in Study Part B1 | Up to 6 months | PFS was defined as time from the date of enrolment to the date of the first documented progressive disease (PD) or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. 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 mm\^2. PFS was censored at the date of the last adequate tumor assessment, if no PFS event was observed prior to the analysis cut-off date. |
| PFS Based on Local Radiology Assessments Using RECIST 1.1 Criteria for Participants by PIK3CA Mutation Status Measured in Baseline Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Study Part A | Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months | PFS in participants with PIK3CA mutation as measured in ctDNA. PFS was defined as time from the date of randomization to the date of the first documented progression or death due to any cause. |
| Post-Hoc: All Collected Deaths | On-treatment deaths: Up to approximately 28 months (Part A) or approximately 17 months (Part B1). Post-treatment survival follow-up deaths: Up to approximately 7 additional months (Part A) or approximately 9 additional months (Part B1). | On-treatment deaths due to any cause were collected from first dose of study medication to 30 days after the last dose of study treatment. Post-treatment survival follow-up deaths were collected from Day 31 after last dose of study medication to the data cut-off date. |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, China, Colombia, Croatia, France, Germany, Hungary, India, Israel, Italy, Malaysia, Mexico, Norway, Peru, Poland, Russia, Slovakia, Slovenia, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: Alpelisib + Nab-paclitaxel Participants received alpelisib 300 mg orally + nab-paclitaxel 100 mg/m\^2 intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle. | 52 |
| Part A: Placebo + Nab-paclitaxel Participants received placebo + nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle. | 50 |
| Part B1: Alpelisib + Nab-paclitaxel Participants received alpelisib 300 mg orally + nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle. | 35 |
| Total | 137 |
Baseline characteristics
| Characteristic | Part A: Alpelisib + Nab-paclitaxel | Part A: Placebo + Nab-paclitaxel | Part B1: Alpelisib + Nab-paclitaxel | Total |
|---|---|---|---|---|
| Age, Continuous | 56.8 years STANDARD_DEVIATION 9.76 | 59.1 years STANDARD_DEVIATION 11.34 | 48.4 years STANDARD_DEVIATION 12.21 | 55.5 years STANDARD_DEVIATION 11.74 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 17 Participants | 19 Participants | 10 Participants | 46 Participants |
| Race/Ethnicity, Customized Black Or African American | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 32 Participants | 30 Participants | 23 Participants | 85 Participants |
| Sex: Female, Male Female | 52 Participants | 49 Participants | 35 Participants | 136 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 52 | 6 / 50 | 3 / 35 | 19 / 46 | 14 / 44 | 11 / 32 |
| other Total, other adverse events | 51 / 52 | 47 / 50 | 34 / 35 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 22 / 52 | 15 / 50 | 14 / 35 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Response Rate (ORR) Based on Local Radiology Assessments in Participants With Measurable Disease at Baseline in Study Part B1
ORR was defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. BOR was defined as the best response recorded from the start of the study treatment until progressive disease (PD)/recurrence. 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. PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; PD= At least a 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Up to 6 months
Population: Part B1: The full analysis set included all participants to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Overall Response Rate (ORR) Based on Local Radiology Assessments in Participants With Measurable Disease at Baseline in Study Part B1 | 14.3 percentage of participants |
Primary
Progression-free Survival (PFS) Per Investigator Assessment in Study Part A
PFS was defined as time from the date of randomization to the date of the first documented progressive disease (PD) or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. 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 mm\^2. PFS was censored at the date of the last adequate tumor assessment, if no PFS event was observed prior to the analysis cut-off date.
Time frame: Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Population: Part A: The full analysis set included all participants to whom study treatment was assigned by randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Progression-free Survival (PFS) Per Investigator Assessment in Study Part A | 7.2 months |
| Part A: Placebo + Nab-paclitaxel | Progression-free Survival (PFS) Per Investigator Assessment in Study Part A | 5.6 months |
95% CI: [0.92, 2.41]Regression, Cox
Secondary
Clinical Benefit Rate (CBR) With Confirmed Response in Study Part A
Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1 based on investigator's assessment. 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 PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time frame: Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Population: Part A: The full analysis set included all participants to whom study treatment was assigned by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Clinical Benefit Rate (CBR) With Confirmed Response in Study Part A | 50.0 percentage of participants |
| Part A: Placebo + Nab-paclitaxel | Clinical Benefit Rate (CBR) With Confirmed Response in Study Part A | 44.0 percentage of participants |
Secondary
Clinical Benefit Rate (CBR) With Confirmed Response in Study Part B1
Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1 based on investigator's assessment. 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 PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time frame: Up to 6 months
Population: Part B1: The full analysis set included all participants to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Clinical Benefit Rate (CBR) With Confirmed Response in Study Part B1 | 25.7 percentage of participants |
Secondary
Duration of Response (DOR) With Confirmed Response in Study Part A
Duration of response (DOR) with confirmed response only applied to participants whose best overall response (BOR) was confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progressive disease (PD) or death due to underlying cancer. 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; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Population: Part A: The full analysis set included all participants to whom study treatment was assigned by randomization. Results are reported for participants whose best overall response was confirmed complete response (CR) or confirmed partial response (PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Duration of Response (DOR) With Confirmed Response in Study Part A | 7.39 months |
| Part A: Placebo + Nab-paclitaxel | Duration of Response (DOR) With Confirmed Response in Study Part A | NA months |
Secondary
Duration of Response (DOR) With Confirmed Response in Study Part B1
Duration of response (DOR) with confirmed response only applied to participants whose best overall response (BOR) was confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progressive disease (PD) or death due to underlying cancer. 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; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to approximately 20 months
Population: Part B1: The full analysis set included all participants to whom study treatment was assigned. Results are reported for participants whose best overall response was confirmed complete response (CR) or confirmed partial response (PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Duration of Response (DOR) With Confirmed Response in Study Part B1 | 11.04 months |
Secondary
Overall Response Rate (ORR) With Confirmed Response in Study Part A
ORR with confirmed response was the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as per local review and according to RECIST 1.1. BOR was defined as the best response recorded from the start of the study treatment until progressive disease (PD)/recurrence. 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. PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; PD= At least a 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Population: Part A: The full analysis set included all participants to whom study treatment was assigned by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Overall Response Rate (ORR) With Confirmed Response in Study Part A | 40.4 percentage of participants |
| Part A: Placebo + Nab-paclitaxel | Overall Response Rate (ORR) With Confirmed Response in Study Part A | 34.0 percentage of participants |
Secondary
Overall Survival in Study Part A
Overall survival is defined as the time from date of randomization to date of death due to any cause.
Time frame: Up to 66 months
Secondary
Overall Survival in Study Part B1
Overall survival for Part B1 was defined as the number of participants who were alive at the end of the post-treatment period.
Time frame: Up to approximately 26 months.
Population: Part B1: All participants to whom study treatment was assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Overall Survival in Study Part B1 | 21 Participants |
Secondary
PFS Based on Local Radiology Assessments Using RECIST 1.1 Criteria for Participants by PIK3CA Mutation Status Measured in Baseline Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Study Part A
PFS in participants with PIK3CA mutation as measured in ctDNA. PFS was defined as time from the date of randomization to the date of the first documented progression or death due to any cause.
Time frame: Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Population: Part A: The full analysis set included all participants to whom study treatment was assigned by randomization. Results are reported for participants with available data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | PFS Based on Local Radiology Assessments Using RECIST 1.1 Criteria for Participants by PIK3CA Mutation Status Measured in Baseline Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Study Part A | 7.5 months |
| Part A: Placebo + Nab-paclitaxel | PFS Based on Local Radiology Assessments Using RECIST 1.1 Criteria for Participants by PIK3CA Mutation Status Measured in Baseline Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Study Part A | 3.5 months |
Secondary
Post-Hoc: All Collected Deaths
On-treatment deaths due to any cause were collected from first dose of study medication to 30 days after the last dose of study treatment. Post-treatment survival follow-up deaths were collected from Day 31 after last dose of study medication to the data cut-off date.
Time frame: On-treatment deaths: Up to approximately 28 months (Part A) or approximately 17 months (Part B1). Post-treatment survival follow-up deaths: Up to approximately 7 additional months (Part A) or approximately 9 additional months (Part B1).
Population: Parts A and B: All participants to whom study treatment was assigned.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Post-Hoc: All Collected Deaths | Post-treatment survival follow-up deaths | 19 Participants |
| Part A: Alpelisib + Nab-paclitaxel | Post-Hoc: All Collected Deaths | On-treatment deaths | 6 Participants |
| Part A: Alpelisib + Nab-paclitaxel | Post-Hoc: All Collected Deaths | All deaths | 25 Participants |
| Part A: Placebo + Nab-paclitaxel | Post-Hoc: All Collected Deaths | Post-treatment survival follow-up deaths | 14 Participants |
| Part A: Placebo + Nab-paclitaxel | Post-Hoc: All Collected Deaths | On-treatment deaths | 6 Participants |
| Part A: Placebo + Nab-paclitaxel | Post-Hoc: All Collected Deaths | All deaths | 20 Participants |
| Part B1: Alpelisib + Nab-paclitaxelEdit | Post-Hoc: All Collected Deaths | On-treatment deaths | 3 Participants |
| Part B1: Alpelisib + Nab-paclitaxelEdit | Post-Hoc: All Collected Deaths | All deaths | 14 Participants |
| Part B1: Alpelisib + Nab-paclitaxelEdit | Post-Hoc: All Collected Deaths | Post-treatment survival follow-up deaths | 11 Participants |
Secondary
Progression-free Survival (PFS) Per Investigator Assessment in Study Part B1
PFS was defined as time from the date of enrolment to the date of the first documented progressive disease (PD) or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. 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 mm\^2. PFS was censored at the date of the last adequate tumor assessment, if no PFS event was observed prior to the analysis cut-off date.
Time frame: Up to 6 months
Population: Part B1: The full analysis set included all participants to whom study treatment was assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Progression-free Survival (PFS) Per Investigator Assessment in Study Part B1 | 3.71 months |
Secondary
Time to Response (TTR) in Study Part A
Time to response (TTR) was defined as the time from the date of randomization/enrolment to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed (although date of initial response is used, not date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1. 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; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Population: Part A: The full analysis set included all participants to whom study treatment was assigned by randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Time to Response (TTR) in Study Part A | NA months |
| Part A: Placebo + Nab-paclitaxel | Time to Response (TTR) in Study Part A | NA months |
Secondary
Time to Response (TTR) in Study Part B1
Time to response (TTR) was defined as the time from the date of randomization/enrolment to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed (although date of initial response was used, not date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1. 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; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to 6 months
Population: Part B1: The full analysis set included all participants to whom study treatment was assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Alpelisib + Nab-paclitaxel | Time to Response (TTR) in Study Part B1 | NA months |