Breast Cancer
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, multicenter, pre-operative Phase II study designed to estimate the efficacy of ipatasertib combined with paclitaxel chemotherapy versus placebo combined with paclitaxel chemotherapy in women with Stage Ia - IIIa triple-negative breast adenocarcinoma. The anticipated time on study treatment is 12 weeks.
Interventions
DRUGIpatasertib
Ipatasertib will be administered at a dose of 400 milligrams (mg) orally daily on Days 1-21 of each 28-day cycle for 3 cycles.
DRUGPaclitaxel
Paclitaxel will be administered at a dose of 80 milligrams per square meter (mg/m\^2) as IV infusion QW for 3 cycles.
DRUGPlacebo
Participants will receive placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles.
Sponsors
SOLTI Breast Cancer Research Group
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Premenopausal or postmenopausal women * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Histologically documented, Stage Ia to operable Stage IIIa, triple-negative carcinoma of the breast with primary tumor greter than or equal to (\>/=) 1.5 centimeters (cm) in largest diameter (cT1-3) by MRI * Adequate hematologic and organ function within 14 days before the first study treatment * Availability of tumor tissue from formalin-fixed, paraffin-embedded (FFPE) core biopsy of breast primary tumor * For female participants of childbearing potential, agreement to use highly effective form(s) of contraception for the duration of the study and for at least 6 months after last dose of study treatment
Exclusion criteria
* Known human epidermal growth factor 2 (HER2)-positive, estrogen receptor (ER)-positive, or progesterone receptor (PgR)-positive breast cancer * Any prior treatment for the current primary invasive breast cancer * Participants with cT4 or cN3 stage breast tumors * Metastatic (Stage IV) breast cancer * Bilateral invasive breast cancer * Multicentric breast cancer * Any disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pathological Complete Response (pCR) in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in All Participants) | Surgery visit (at approximately Weeks 14 to 19) | pCR was defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer (AJCC) Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes. |
| Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Have Phosphatase and Tensin Homolog [PTEN]-Low Tumors) | Surgery visit (at approximately Weeks 14 to 19) | pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Tumor Response by Magnetic Resonance Imaging (MRI), As Assessed by Investigator Per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) (in All Participants) | Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16]) | Objective tumor response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
| Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Diagnostic Positive [Dx+]) | Surgery visit (at approximately Weeks 14 to 19) | pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes. |
| Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors) | Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16]) | ORR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. ORR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
| Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Dx+) | Surgery visit (at approximately Weeks 14 to 19) | pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue. |
| Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | Surgery visit (at approximately Weeks 14 to 19) | pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast subtypes by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue. The intrinsic molecular subtypes of breast cancer included here are luminal A (LumA), Her-2, basal-like, normal and unknown. |
| Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants) | Surgery visit (at approximately Weeks 14 to 19) | pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue. |
| Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors | From screening to surgery visit (at approximately Weeks 14 to 19) | After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across. |
| Percentage of Participants With Adverse Events | Screening up to Week 24 | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Plasma Concentrations of Ipatasertib on Day 1 and Day 8 | 0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days) | Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants. |
| Minimum Observed Plasma Concentration (Cmin) of Ipatasertib | 0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days) | Plasma samples for pharmacokinetic characterization was collected on Day 1 and Day 8 in all participants. |
| Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors | Surgery visit (at approximately Weeks 14 to 19) | After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across. |
| Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Have PTEN-low Tumors) | Surgery visit (at approximately Weeks 14 to 19) | pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue. |
Countries
Portugal, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ipatasertib + Paclitaxel Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses). | 76 |
| Placebo + Paclitaxel Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses). | 75 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 3 | 2 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Unknown Reason | 1 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo + Paclitaxel | Total | Ipatasertib + Paclitaxel |
|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 12 | 53.8 years STANDARD_DEVIATION 11.5 | 53.8 years STANDARD_DEVIATION 10.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 70 Participants | 141 Participants | 71 Participants |
| Sex: Female, Male Female | 75 Participants | 151 Participants | 76 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 76 | 0 / 75 |
| other Total, other adverse events | 76 / 76 | 73 / 75 |
| serious Total, serious adverse events | 10 / 76 | 3 / 75 |
Outcome results
Primary
Percentage of Participants With Pathological Complete Response (pCR) in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in All Participants)
pCR was defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer (AJCC) Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
Time frame: Surgery visit (at approximately Weeks 14 to 19)
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With Pathological Complete Response (pCR) in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in All Participants) | 17.1 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With Pathological Complete Response (pCR) in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in All Participants) | 13.3 percentage of participants |
Comparison: Unstratified Analysisp-value: 0.51995% CI: [-8.99, 16.54]Chi-squared
Primary
Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Have Phosphatase and Tensin Homolog [PTEN]-Low Tumors)
pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
Time frame: Surgery visit (at approximately Weeks 14 to 19)
Population: The ITT population included all randomized participants who have PTEN-low tumors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Have Phosphatase and Tensin Homolog [PTEN]-Low Tumors) | 15.8 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Have Phosphatase and Tensin Homolog [PTEN]-Low Tumors) | 12.5 percentage of participants |
Comparison: Unstratified analysisp-value: 0.781795% CI: [-25.52, 32.1]Chi-squared
Secondary
Minimum Observed Plasma Concentration (Cmin) of Ipatasertib
Plasma samples for pharmacokinetic characterization was collected on Day 1 and Day 8 in all participants.
Time frame: 0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)
Population: The ITT population included all participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ipatasertib + Paclitaxel | Minimum Observed Plasma Concentration (Cmin) of Ipatasertib | 37.5 ng/mL | Standard Deviation 28.3 |
Secondary
Percentage of Participants With Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Screening up to Week 24
Population: The safety population was identical to the ITT population and included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With Adverse Events | 100 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With Adverse Events | 98.7 percentage of participants |
Secondary
Percentage of Participants With Objective Tumor Response by Magnetic Resonance Imaging (MRI), As Assessed by Investigator Per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) (in All Participants)
Objective tumor response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With Objective Tumor Response by Magnetic Resonance Imaging (MRI), As Assessed by Investigator Per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) (in All Participants) | 67.1 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With Objective Tumor Response by Magnetic Resonance Imaging (MRI), As Assessed by Investigator Per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) (in All Participants) | 56.0 percentage of participants |
Comparison: Unstratified analysisp-value: 0.160795% CI: [-5.64, 27.85]Chi-squared
Secondary
Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors)
ORR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. ORR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])
Population: The ITT population included all randomized participants who have PTEN-low tumors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors) | 73.7 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors) | 50.0 percentage of participants |
Comparison: Unstratified Analysisp-value: 0.148695% CI: [-13.57, 60.94]Chi-squared
Secondary
Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype
pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast subtypes by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue. The intrinsic molecular subtypes of breast cancer included here are luminal A (LumA), Her-2, basal-like, normal and unknown.
Time frame: Surgery visit (at approximately Weeks 14 to 19)
Population: The ITT population included all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | Unknown | 18.5 percentage of participants |
| Ipatasertib + Paclitaxel | Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | Basal | 22.0 percentage of participants |
| Ipatasertib + Paclitaxel | Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | Normal | 50.0 percentage of participants |
| Ipatasertib + Paclitaxel | Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | Her2 | 33.3 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | Basal | 10.8 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | Normal | 0 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | Unknown | 21.9 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | Her2 | 0 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype | LumA | 0 percentage of participants |
Secondary
Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Diagnostic Positive [Dx+])
pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
Time frame: Surgery visit (at approximately Weeks 14 to 19)
Population: The ITT population included all randomized participants who are Akt Dx+.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Diagnostic Positive [Dx+]) | 17.9 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Diagnostic Positive [Dx+]) | 11.8 percentage of participants |
p-value: 0.49895% CI: [-15.01, 27.2]Chi-squared
Secondary
Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants)
pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Time frame: Surgery visit (at approximately Weeks 14 to 19)
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants) | 22.4 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants) | 14.7 percentage of participants |
Comparison: Unstratified analysisp-value: 0.223495% CI: [-5.95, 21.35]Chi-squared
Secondary
Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Dx+)
pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Time frame: Surgery visit (at approximately Weeks 14 to 19)
Population: The ITT population included all randomized participants who are Akt Dx+.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Dx+) | 21.4 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Dx+) | 11.8 percentage of participants |
p-value: 0.303295% CI: [-12.25, 31.58]Chi-squared
Secondary
Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Have PTEN-low Tumors)
pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Time frame: Surgery visit (at approximately Weeks 14 to 19)
Population: The ITT population included all randomized participants who have PTEN-low tumors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Have PTEN-low Tumors) | 15.8 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Have PTEN-low Tumors) | 18.8 percentage of participants |
Comparison: Unstratified analysisp-value: 0.816995% CI: [-33.91, 27.99]Chi-squared
Secondary
Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors
After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.
Time frame: From screening to surgery visit (at approximately Weeks 14 to 19)
Population: The ITT population included all randomized participants with T2 or T3 Tumors with response to conversion to BCS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors | 33.3 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors | 25 percentage of participants |
p-value: 0.629195% CI: [-33.04, 49.71]Chi-squared
Secondary
Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors
After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.
Time frame: Surgery visit (at approximately Weeks 14 to 19)
Population: The ITT population included all randomized participants with T2 or T3 Tumors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipatasertib + Paclitaxel | Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors | 64.5 percentage of participants |
| Placebo + Paclitaxel | Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors | 60.3 percentage of participants |
p-value: 0.62895% CI: [-14.37, 22.76]Chi-squared
Secondary
Plasma Concentrations of Ipatasertib on Day 1 and Day 8
Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Time frame: 0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)
Population: The ITT population included all randomized participants. Reported here are data for participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ipatasertib + Paclitaxel | Plasma Concentrations of Ipatasertib on Day 1 and Day 8 | 0.5 hours | 290 ng/mL | Standard Deviation 312 |
| Ipatasertib + Paclitaxel | Plasma Concentrations of Ipatasertib on Day 1 and Day 8 | 4 hours | 196 ng/mL | Standard Deviation 93 |
| Ipatasertib + Paclitaxel | Plasma Concentrations of Ipatasertib on Day 1 and Day 8 | 166 hours | 37.5 ng/mL | Standard Deviation 28.3 |
| Ipatasertib + Paclitaxel | Plasma Concentrations of Ipatasertib on Day 1 and Day 8 | 170 hours | 355 ng/mL | Standard Deviation 204 |