Metastatic Prostate Cancer
Conditions
Keywords
Metastatic Castrate-Resistant Prostate Cancer
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of ipatasertib plus abiraterone and prednisone/prednisolone compared with placebo plus abiraterone and prednisone/prednisolone in participants with metastatic castrate-resistant prostate cancer (mCRPC).
Interventions
DRUGIpatasertib
Oral tablets, 400 mg, given once daily (QD) beginning on Day 1 of Cycle 1 until disease progression or intolerable toxicity.
DRUGAbiraterone
Oral tablets of abiraterone, 1000 mg QD, taken on an empty stomach and swallowed whole with water.
DRUGPlacebo
Oral tablets (matched to ipatasertib appearance), given QD beginning on Day 1 of Cycle 1 until disease progression or intolerable toxicity.
Oral tablets of 5 mg, taken twice daily (BID) until disease progression or intolerable toxicity.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Collaborative Oncology Group (ECOG) performance status of 0 or 1 at screening * Adequate hematologic and organ function within 28 days before the first study treatment * Ability to comply with the study protocol, in the investigator's judgment * Willingness and ability of participants to use the electronic device to report selected study outcomes; Caregivers and site staff can assist with patient diary input but patient must be able to independently comprehend and answer the questionnaires * Life expectancy of at least 6 months * Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm * For enrollment into the China extension cohort, residence in the People's Republic of China Disease-specific Inclusion Criteria: * Histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small-cell features * Consent to provide a formalin-fixed paraffin-embedded (FFPE) tissue block (preferred) or a minimum of 15 (20 preferred) freshly cut unstained tumor slides from the most recently collected, available tumor tissue accompanied by an associated pathology report (with tumor content information, Gleason score, and disease staging) for PTEN IHC and NGS testing and for other protocol-mandated secondary and exploratory assessments. If only 12-14 slides are available, the patient may still be eligible for the study, after discussion with and approval by the Medical Monitor. Cytologic or fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases is not acceptable * A valid PTEN IHC result (testingcentral laboratory tested with results directly sent to IxRS) (e.g., participants with an invalid or failed PTEN IHC result are not permitted to enroll) * Metastatic disease documented prior to randomization by clear evidence of bone lesions on bone scan and/or measurable soft tissue disease by computed tomography (CT) and/or magnetic resonance imaging (MRI) (at least one target lesion) according to RECIST v1.1 * Asymptomatic or mildly symptomatic form of prostate cancer * Progressive disease before initiating study treatment * Ongoing androgen deprivation with gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy, with serum testosterone \<= 50 ng/dL (\<= 1.7 nmol/L) within 28 days before randomization
Exclusion criteria
* Inability or unwillingness to swallow whole pills * History of malabsorption syndrome or other condition that would interfere with enteral absorption * Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including cirrhosis, current alcohol abuse, or current known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) * Need of more than 10 mg/day of prednisone or an equivalent dose of other anti-inflammatory corticosteroids as a current systemic corticosteroid therapy to treat a chronic disease (e.g., rheumatic disorder) * Active infection requiring intravenous (IV) antibiotics within 14 days before Day 1, Cycle 1 * Immunocompromised status because of current known active infection with HIV or because of the use of immunosuppressive therapies for other conditions * Major surgical procedure or significant traumatic injury within 28 days prior to Day 1, Cycle 1, or anticipation of the need for major surgery during study treatment * History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), untreated coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), myocardial infarction or atrial thrombotic events within the past 6 months, severe unstable angina, New York Heart Association Class III and IV heart disease or depressed left ventricular ejection fraction (LVEF; previously documented LVEF \< 50% without documentation of recovery), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome * History of another malignancy within 5 years prior to randomization, except for either adequately treated non-melanomatous carcinoma of the skin, adequately treated melanoma in situ, adequately treated non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta, and low grade T1 tumors), or other malignancies where the patient has undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to have a recurrence rate of \<5% at 5 years * Any other diseases, cardiovascular, pulmonary, or metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participants at high risk from treatment complications. Disease-Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed Radiographic Progression-free Survival (rPFS), Per Prostate Cancer Working Group 3 (PCWG3) Criteria in Phosphatase and Tensin Homolog (PTEN) Loss Population | Up to approximately 32 months | rPFS was defined as time from date of randomization to the first occurrence of documented disease progression (PD), as assessed by the investigator with use of the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm) in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later according to the PCWG3 criteria. The Kaplan-Meier (KM) estimate was used to determine the median rPFS. |
| Investigator-assessed rPFS, Per PCWG3 Criteria in ITT Population | Up to approximately 32 months | rPFS was defined as time from date of randomization to the first occurrence of documented PD, as assessed by the investigator with use of the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions according to RECIST v1.1 criteria. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later according to the PCWG3 criteria. The KM estimate was used to determine the median rPFS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS in ITT Population | Up to approximately 6.5 years | OS was defined as the time from randomization to death due to any cause. KM estimates were used to determine the median OS. |
| Time to Pain Progression in PTEN-loss Population | Up to approximately 5.5 years | Time to pain progression was defined as the time from randomization to the first occurrence of confirmed clinically meaningful cancer-related pain progression event. Cancer-related pain progression refers to pain onset for participants who were asymptomatic at baseline or pain worsening for those who were mildly symptomatic at baseline. Pain severity was graded on a 10-point numeric rating scale \[NRS\], with 0=no pain and 10=severe pain. Pain severity progression was defined as a ≥ 2-point absolute increase from baseline. KM estimates were used to determine the median time to pain progression. |
| Time to Pain Progression in ITT Population | Up to approximately 5.5 years | Time to pain progression was defined as the time from randomization to the first occurrence of confirmed clinically meaningful cancer-related pain progression event. Cancer-related pain progression refers to pain onset for participants who were asymptomatic at baseline or pain worsening for those who were mildly symptomatic at baseline. Pain severity was graded on a 10-point NRS, with 0=no pain and 10=severe pain. Pain severity progression was defined as a ≥ 2-point absolute increase from baseline. KM estimates were used to determine the median time to pain progression. |
| Time to Initiation of Cytotoxic Chemotherapy for Prostate Cancer (PC) in PTEN-loss Population | Up to approximately 5.5 years | Time to initiation of cytotoxic chemotherapy was defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for PC. KM estimates were used to determine the median time to initiation of cytotoxic chemotherapy. |
| Time to Initiation of Cytotoxic Chemotherapy for PC in ITT Population | Up to approximately 5.5 years | Time to initiation of cytotoxic chemotherapy was defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for PC. KM estimates were used to determine the median time to initiation of cytotoxic chemotherapy. |
| Time to Function Deterioration Per European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Physical Function (PF) Scale and Role Function (RF) Scale in PTEN-loss Population | Up to approximately 5.5 years | Time to function deterioration=time from date of randomization to date of 10-point or more score decrease on either EORTC QLQ-C30 5-item PF/2-item RF scale scores, held for two consecutive assessments or death within 28 days, whichever occurs first. EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical,emotional,role,cognitive&social), 3 symptom scales (fatigue,nausea&vomiting,pain), global health/quality of life (GHS/QoL)&6 single items (dyspnea,insomnia,appetite loss,constipation,diarrhea&financial difficulties). PF scale has 5 questions about participants physical functioning&daily activities. RF scale has 2 questions about work/daily activities&hobbies/leisurely activities. PF&RF are scored on a 4-point scale (1=Not at All to 4=Very Much). Obtained scores are linearly transformed to score range of 0-100, where higher scores indicate a higher response level (better PF)&better functioning/support. |
| Time to Function Deterioration Per EORTC QLQ-C30 PF Scale and RF Scale in ITT Population | Up to approximately 5.5 years | Time to function deterioration=time from date of randomization to date of 10-point or more score decrease on either EORTC QLQ-C30 5-item PF/2-item RF scale scores, held for two consecutive assessments or death within 28 days, whichever occurs first. EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical,emotional,role,cognitive & social), 3 symptom scales (fatigue,nausea&vomiting,pain), GHS/QoL & 6 single items (dyspnea,insomnia,appetite loss,constipation,diarrhea & financial difficulties). PF scale has 5 questions about participants physical functioning & daily activities. RF scale has 2 questions about work/daily activities & hobbies/leisurely activities. PF&RF are scored on a 4-point scale (1=Not at All to 4=Very Much). Obtained scores are linearly transformed to score range of 0-100, where higher scores indicate a higher response level (better PF) & better functioning/support. |
| Time to Prostate-specific Antigen (PSA) Progression, Per the PCWG3 Criteria in PTEN-loss Population | Up to approximately 5.5 years | Time to PSA progression was defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression was defined as a PSA increase that was ≥ 25% and ≥ 2 nanograms per milliliters (ng/mL) above the baseline or the nadir, which was confirmed by a second value ≥ 3 weeks later. KM estimate was used to determine the median time to PSA. |
| Time to First Opioid Use in PTEN-loss Population | Up to approximately 5.5 years | Time to first opioid use was defined as the time interval from the date of randomization to the date of an initiation of opioid analgesic use for cancer-related pain, and consumption reported on at least 7 consecutive days. KM estimate was used to determine the median time to first opioid use. |
| Time to First Opioid Use in ITT Population | Up to approximately 5.5 years | Time to first opioid use was defined as the time interval from the date of randomization to the date of an initiation of opioid analgesic use for cancer-related pain, and consumption reported on at least 7 consecutive days. KM estimate was used to determine the median time to first opioid use. |
| Time to Symptomatic Skeletal Event (SSE) in PTEN-loss Population | Up to approximately 5.5 years | Time to SSE was defined as the time from randomization to the first occurrence of an SSE. A SSE was defined using one of the following: use of external-beam radiotherapy to relieve skeletal symptoms (including initiation of radium-223 to treat symptoms of bone metastases); occurrence of a new symptomatic pathological bone fracture (vertebral or non-vertebral); clinically apparent occurrence of spinal cord compression, or a tumor-related orthopedic surgical intervention. KM estimates were used to determine the median time to SSE. |
| Time to PSA Progression, Per the PCWG3 Criteria in ITT Population | Up to approximately 5.5 years | Time to PSA progression was defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression was defined as a PSA increase that was ≥ 25% and ≥ 2 ng/mL above the baseline or the nadir, which was confirmed by a second value ≥ 3 weeks later. KM estimate was used to determine the median time to PSA. |
| Objective Response Rate (ORR) Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in PTEN-loss Population | Up to approximately 5.5 years | ORR was defined as the percentage of participants who had an objective response (OR) with measurable disease at baseline. An OR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator using RECIST v1.1 and PCWG3 criteria in participants with measurable disease at baseline. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method. Percentages have been rounded off. |
| ORR Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in ITT Population | Up to approximately 5.5 years | ORR was defined as the percentage of participants who had an OR with measurable disease at baseline. An OR was defined as a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator using RECIST v1.1 and PCWG3 criteria in participants with measurable disease at baseline. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method. Percentage have been rounded off. |
| Duration of Confirmed Response (DOCR) in PTEN-loss Population | Up to approximately 5.5 years | DOCR was defined as the time from the first documented OR (CR or PR) to documented PD as determined by the investigator using RECIST v1.1 and PCWG3 criteria, or death from any cause, whichever occurred first. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions. DOR was estimated using the KM methodology. |
| DOCR in ITT Population | Up to approximately 5.5 years | DOCR was defined as the time from the first documented OR (CR or PR) to documented PD as determined by the investigator using RECIST v1.1 and PCWG3 criteria, or death from any cause, whichever occured first. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions. DOR was estimated using the KM methodology. |
| PSA Response Rate in PTEN-loss Population | Up to approximately 5.5 years | PSA response rate was defined as the percentage of participants achieving a PSA decline ≥ 50% from baseline. Participants without a post-baseline PSA assessment were considered to be non-responders. Percentages have been rounded off. |
| PSA Response Rate in ITT Population | Up to approximately 5.5 years | PSA response rate was defined as the percentage of participants achieving a PSA decline ≥ 50% from baseline. Participants without a post-baseline PSA assessment were considered to be non-responders. Percentages have been rounded off. |
| Investigator-assessed rPFS Per PCWG3 Criteria in PTEN-loss Population by Next-generation Sequencing (NGS) | Up to approximately 32 months | rPFS was defined as time from date of randomization to the first occurrence of documented PD, as assessed by the investigator using the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later. |
| Percentage of Participants With Adverse Events (AEs) | Up to 28 days after last study drug administration (approximately 6.5 years) | An AE was 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 AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), 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 were also considered as AEs. Percentages have been rounded off. |
| Plasma Concentrations of Ipatasertib at Specified Timepoints | 1-3 hours post-dose (Cycle 1, Day 1; Cycle 1 Day 15 and Cycle 3 Day 1) and pre-dose at steady state (Cycle 1 Day 15, Cycle 3 Day 1, Cycle 6 Day 1) (each cycle length= 28 days) | Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants. |
| Plasma Concentrations of Abiraterone at Specified Timepoints | Pre-dose at steady state in Cycle 1, Day 15 and Cycle 3 Day 1 (each cycle length= 28 days) | Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants. |
| Time to SSE in ITT Population | Up to approximately 5.5 years | Time to SSE was defined as the time from randomization to the first occurrence of an SSE. A SSE was defined using one of the following: use of external-beam radiotherapy to relieve skeletal symptoms (including initiation of radium-223 to treat symptoms of bone metastases); occurrence of a new symptomatic pathological bone fracture (vertebral or non-vertebral); clinically apparent occurrence of spinal cord compression, or a tumor-related orthopedic surgical intervention. KM estimates were used to determine the median time to SSE. |
| Overall Survival (OS) in PTEN-loss Population | Up to approximately 6.5 years | OS was defined as the time from randomization to death due to any cause. KM estimates were used to determine the median OS. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Costa Rica, Denmark, France, Greece, Hungary, Ireland, Israel, Italy, Japan, Mexico, Norway, Poland, Portugal, Russia, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
A total of 1101 male participants with metastatic castrate-resistant prostate cancer (mCRPC) took part in the study at 181 investigative sites across 26 countries from June 30, 2017 to April 24, 2024.
Pre-assignment details
Participants were randomized in a 1:1 ratio to one of the two following treatment arms: abiraterone plus prednisone/prednisolone plus ipatasertib (Ipat + Abi) and abiraterone plus prednisone/prednisolone plus placebo (Pbo + Abi). 3 participants in the Pbo+Abi arm and 1 participant in the Ipat +Abi arm did not receive any treatment. 5 participants randomized to the placebo arm took at least one dose of ipatasertib and hence were included in the Ipat + Abi arm for safety analysis.
Participants by arm
| Arm | Count |
|---|---|
| Pbo + Abi Participants received matching placebo along with abiraterone 1000 mg, QD and prednisone/prednisolone, 5 mg, BID administered orally in each 28 day treatment cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. | 554 |
| Ipat + Abi Participants received ipatasertib, 400 mg, QD along with abiraterone, 1000 mg, QD and prednisone/prednisolone, 5 mg, BID administered orally in each 28 day treatment cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. | 547 |
| Total | 1,101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 351 | 318 |
| Overall Study | Lost to Follow-up | 14 | 5 |
| Overall Study | Physician Decision | 4 | 6 |
| Overall Study | Progressive Disease | 3 | 4 |
| Overall Study | Reason Not Specified | 138 | 150 |
| Overall Study | Withdrawal by Subject | 44 | 64 |
Baseline characteristics
| Characteristic | Pbo + Abi | Total | Ipat + Abi |
|---|---|---|---|
| Age, Continuous | 69.7 years STANDARD_DEVIATION 8.2 | 69.5 years STANDARD_DEVIATION 8.1 | 69.4 years STANDARD_DEVIATION 8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 16 Participants | 31 Participants | 15 Participants |
| Race/Ethnicity, Customized Asian | 109 Participants | 219 Participants | 110 Participants |
| Race/Ethnicity, Customized Black or African American | 9 Participants | 19 Participants | 10 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 65 Participants | 131 Participants | 66 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 469 Participants | 921 Participants | 452 Participants |
| Race/Ethnicity, Customized Not Stated | 13 Participants | 27 Participants | 14 Participants |
| Race/Ethnicity, Customized Unknown | 33 Participants | 22 Participants | 35 Participants |
| Race/Ethnicity, Customized White | 386 Participants | 762 Participants | 376 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 554 Participants | 1101 Participants | 547 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 358 / 546 | 331 / 551 |
| other Total, other adverse events | 496 / 546 | 541 / 551 |
| serious Total, serious adverse events | 158 / 546 | 252 / 551 |
Outcome results
Primary
Investigator-assessed Radiographic Progression-free Survival (rPFS), Per Prostate Cancer Working Group 3 (PCWG3) Criteria in Phosphatase and Tensin Homolog (PTEN) Loss Population
rPFS was defined as time from date of randomization to the first occurrence of documented disease progression (PD), as assessed by the investigator with use of the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm) in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later according to the PCWG3 criteria. The Kaplan-Meier (KM) estimate was used to determine the median rPFS.
Time frame: Up to approximately 32 months
Population: PTEN loss population included all randomized participants with PTEN loss tumors by immunohistochemistry (IHC), regardless of whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Investigator-assessed Radiographic Progression-free Survival (rPFS), Per Prostate Cancer Working Group 3 (PCWG3) Criteria in Phosphatase and Tensin Homolog (PTEN) Loss Population | 16.5 months |
| Ipat + Abi | Investigator-assessed Radiographic Progression-free Survival (rPFS), Per Prostate Cancer Working Group 3 (PCWG3) Criteria in Phosphatase and Tensin Homolog (PTEN) Loss Population | 18.5 months |
p-value: 0.033595% CI: [0.61, 0.98]Log Rank
Primary
Investigator-assessed rPFS, Per PCWG3 Criteria in ITT Population
rPFS was defined as time from date of randomization to the first occurrence of documented PD, as assessed by the investigator with use of the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions according to RECIST v1.1 criteria. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later according to the PCWG3 criteria. The KM estimate was used to determine the median rPFS.
Time frame: Up to approximately 32 months
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Investigator-assessed rPFS, Per PCWG3 Criteria in ITT Population | 16.6 months |
| Ipat + Abi | Investigator-assessed rPFS, Per PCWG3 Criteria in ITT Population | 19.2 months |
p-value: 0.043195% CI: [0.71, 0.99]Log Rank
Secondary
DOCR in ITT Population
DOCR was defined as the time from the first documented OR (CR or PR) to documented PD as determined by the investigator using RECIST v1.1 and PCWG3 criteria, or death from any cause, whichever occured first. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions. DOR was estimated using the KM methodology.
Time frame: Up to approximately 5.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment. Overall number analyzed is the number of participants with objective response i.e. responders.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | DOCR in ITT Population | 16.3 months |
| Ipat + Abi | DOCR in ITT Population | 18.2 months |
Secondary
Duration of Confirmed Response (DOCR) in PTEN-loss Population
DOCR was defined as the time from the first documented OR (CR or PR) to documented PD as determined by the investigator using RECIST v1.1 and PCWG3 criteria, or death from any cause, whichever occurred first. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions. DOR was estimated using the KM methodology.
Time frame: Up to approximately 5.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment. Overall number analyzed is the number of participants with objective response i.e. responders.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Duration of Confirmed Response (DOCR) in PTEN-loss Population | 14.4 months |
| Ipat + Abi | Duration of Confirmed Response (DOCR) in PTEN-loss Population | 19.6 months |
Secondary
Investigator-assessed rPFS Per PCWG3 Criteria in PTEN-loss Population by Next-generation Sequencing (NGS)
rPFS was defined as time from date of randomization to the first occurrence of documented PD, as assessed by the investigator using the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later.
Time frame: Up to approximately 32 months
Population: PTEN loss population included all randomized participants with PTEN loss tumors by NGS, regardless of whether or not the participant received the assigned treatment. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Investigator-assessed rPFS Per PCWG3 Criteria in PTEN-loss Population by Next-generation Sequencing (NGS) | 14.2 months |
| Ipat + Abi | Investigator-assessed rPFS Per PCWG3 Criteria in PTEN-loss Population by Next-generation Sequencing (NGS) | 19.1 months |
p-value: 0.024695% CI: [0.45, 0.95]Log Rank
Secondary
Objective Response Rate (ORR) Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in PTEN-loss Population
ORR was defined as the percentage of participants who had an objective response (OR) with measurable disease at baseline. An OR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator using RECIST v1.1 and PCWG3 criteria in participants with measurable disease at baseline. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method. Percentages have been rounded off.
Time frame: Up to approximately 5.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment. Overall number analyzed is the number of participants with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pbo + Abi | Objective Response Rate (ORR) Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in PTEN-loss Population | 42.7 percentage of participants |
| Ipat + Abi | Objective Response Rate (ORR) Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in PTEN-loss Population | 63.6 percentage of participants |
p-value: 0.00395% CI: [6.2, 35.65]Cochran-Mantel-Haenszel
Secondary
ORR Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in ITT Population
ORR was defined as the percentage of participants who had an OR with measurable disease at baseline. An OR was defined as a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator using RECIST v1.1 and PCWG3 criteria in participants with measurable disease at baseline. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method. Percentage have been rounded off.
Time frame: Up to approximately 5.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment. Overall number analyzed is the number of participants with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pbo + Abi | ORR Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in ITT Population | 46.2 percentage of participants |
| Ipat + Abi | ORR Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in ITT Population | 62.7 percentage of participants |
p-value: 0.000895% CI: [6.66, 26.27]Cochran-Mantel-Haenszel
Secondary
OS in ITT Population
OS was defined as the time from randomization to death due to any cause. KM estimates were used to determine the median OS.
Time frame: Up to approximately 6.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | OS in ITT Population | 36.5 months |
| Ipat + Abi | OS in ITT Population | 39.4 months |
p-value: 0.251595% CI: [0.79, 1.07]Log Rank
Secondary
Overall Survival (OS) in PTEN-loss Population
OS was defined as the time from randomization to death due to any cause. KM estimates were used to determine the median OS.
Time frame: Up to approximately 6.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Overall Survival (OS) in PTEN-loss Population | 35.8 months |
| Ipat + Abi | Overall Survival (OS) in PTEN-loss Population | 36.8 months |
p-value: 0.569895% CI: [0.76, 1.17]Log Rank
Secondary
Percentage of Participants With Adverse Events (AEs)
An AE was 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 AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), 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 were also considered as AEs. Percentages have been rounded off.
Time frame: Up to 28 days after last study drug administration (approximately 6.5 years)
Population: SE population included all participants who received any amount of the study treatment. 5 participants randomized to the placebo arm took at least one dose of ipatasertib and hence were included in the Ipat + Abi arm for safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pbo + Abi | Percentage of Participants With Adverse Events (AEs) | 96.2 percentage of participants |
| Ipat + Abi | Percentage of Participants With Adverse Events (AEs) | 99.6 percentage of participants |
Secondary
Plasma Concentrations of Abiraterone at Specified Timepoints
Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Time frame: Pre-dose at steady state in Cycle 1, Day 15 and Cycle 3 Day 1 (each cycle length= 28 days)
Population: PK-evaluable population included all participants who received abiraterone treatment with evaluable PK samples. Overall number analyzed is the number of participants with data available for analysis. Number analyzed are unique number of participants out of all the assessed participants with data available at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pbo + Abi | Plasma Concentrations of Abiraterone at Specified Timepoints | Cycle 3 Day 1 | 10.4 ng/mL | Geometric Coefficient of Variation 120 |
| Pbo + Abi | Plasma Concentrations of Abiraterone at Specified Timepoints | Cycle 1 Day 15 | 11.2 ng/mL | Geometric Coefficient of Variation 124 |
| Ipat + Abi | Plasma Concentrations of Abiraterone at Specified Timepoints | Cycle 3 Day 1 | 9.55 ng/mL | Geometric Coefficient of Variation 159 |
| Ipat + Abi | Plasma Concentrations of Abiraterone at Specified Timepoints | Cycle 1 Day 15 | 9.40 ng/mL | Geometric Coefficient of Variation 159 |
Secondary
Plasma Concentrations of Ipatasertib at Specified Timepoints
Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Time frame: 1-3 hours post-dose (Cycle 1, Day 1; Cycle 1 Day 15 and Cycle 3 Day 1) and pre-dose at steady state (Cycle 1 Day 15, Cycle 3 Day 1, Cycle 6 Day 1) (each cycle length= 28 days)
Population: Pharmacokinetic (PK)-evaluable population included all participants who received ipatasertib treatment with evaluable PK samples. Number analyzed per timepoint are unique number of participants out all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pbo + Abi | Plasma Concentrations of Ipatasertib at Specified Timepoints | Cycle 1 Day 1 Post-dose | 212 ng/mL | Geometric Coefficient of Variation 158 |
| Pbo + Abi | Plasma Concentrations of Ipatasertib at Specified Timepoints | Cycle 1 Day 15 Pre-dose | 46.8 ng/mL | Geometric Coefficient of Variation 160 |
| Pbo + Abi | Plasma Concentrations of Ipatasertib at Specified Timepoints | Cycle 1 Day 15 Post-dose | 247 ng/mL | Geometric Coefficient of Variation 138 |
| Pbo + Abi | Plasma Concentrations of Ipatasertib at Specified Timepoints | Cycle 3 Day 1 Pre-dose | 35.4 ng/mL | Geometric Coefficient of Variation 256 |
| Pbo + Abi | Plasma Concentrations of Ipatasertib at Specified Timepoints | Cycle 3 Day 1 Post-dose | 207 ng/mL | Geometric Coefficient of Variation 156 |
| Pbo + Abi | Plasma Concentrations of Ipatasertib at Specified Timepoints | Cycle 6 Day 1 Pre-dose | 46.1 ng/mL | Geometric Coefficient of Variation 134 |
Secondary
PSA Response Rate in ITT Population
PSA response rate was defined as the percentage of participants achieving a PSA decline ≥ 50% from baseline. Participants without a post-baseline PSA assessment were considered to be non-responders. Percentages have been rounded off.
Time frame: Up to approximately 5.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment. Overall number analyzed included participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pbo + Abi | PSA Response Rate in ITT Population | 75.5 percentage of participants |
| Ipat + Abi | PSA Response Rate in ITT Population | 81.3 percentage of participants |
p-value: 0.017895% CI: [0.83, 10.9]Cochran-Mantel-Haenszel
Secondary
PSA Response Rate in PTEN-loss Population
PSA response rate was defined as the percentage of participants achieving a PSA decline ≥ 50% from baseline. Participants without a post-baseline PSA assessment were considered to be non-responders. Percentages have been rounded off.
Time frame: Up to approximately 5.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pbo + Abi | PSA Response Rate in PTEN-loss Population | 71.6 percentage of participants |
| Ipat + Abi | PSA Response Rate in PTEN-loss Population | 83.5 percentage of participants |
p-value: 0.001295% CI: [4.34, 19.29]Cochran-Mantel-Haenszel
Secondary
Time to First Opioid Use in ITT Population
Time to first opioid use was defined as the time interval from the date of randomization to the date of an initiation of opioid analgesic use for cancer-related pain, and consumption reported on at least 7 consecutive days. KM estimate was used to determine the median time to first opioid use.
Time frame: Up to approximately 5.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to First Opioid Use in ITT Population | NA months |
| Ipat + Abi | Time to First Opioid Use in ITT Population | NA months |
p-value: 0.139895% CI: [0.68, 1.06]Log Rank
Secondary
Time to First Opioid Use in PTEN-loss Population
Time to first opioid use was defined as the time interval from the date of randomization to the date of an initiation of opioid analgesic use for cancer-related pain, and consumption reported on at least 7 consecutive days. KM estimate was used to determine the median time to first opioid use.
Time frame: Up to approximately 5.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to First Opioid Use in PTEN-loss Population | NA months |
| Ipat + Abi | Time to First Opioid Use in PTEN-loss Population | NA months |
p-value: 0.135995% CI: [0.57, 1.08]Log Rank
Secondary
Time to Function Deterioration Per EORTC QLQ-C30 PF Scale and RF Scale in ITT Population
Time to function deterioration=time from date of randomization to date of 10-point or more score decrease on either EORTC QLQ-C30 5-item PF/2-item RF scale scores, held for two consecutive assessments or death within 28 days, whichever occurs first. EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical,emotional,role,cognitive & social), 3 symptom scales (fatigue,nausea&vomiting,pain), GHS/QoL & 6 single items (dyspnea,insomnia,appetite loss,constipation,diarrhea & financial difficulties). PF scale has 5 questions about participants physical functioning & daily activities. RF scale has 2 questions about work/daily activities & hobbies/leisurely activities. PF&RF are scored on a 4-point scale (1=Not at All to 4=Very Much). Obtained scores are linearly transformed to score range of 0-100, where higher scores indicate a higher response level (better PF) & better functioning/support.
Time frame: Up to approximately 5.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to Function Deterioration Per EORTC QLQ-C30 PF Scale and RF Scale in ITT Population | 14.8 months |
| Ipat + Abi | Time to Function Deterioration Per EORTC QLQ-C30 PF Scale and RF Scale in ITT Population | 9.2 months |
p-value: 0.007195% CI: [1.06, 1.47]Log Rank
Secondary
Time to Function Deterioration Per European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Physical Function (PF) Scale and Role Function (RF) Scale in PTEN-loss Population
Time to function deterioration=time from date of randomization to date of 10-point or more score decrease on either EORTC QLQ-C30 5-item PF/2-item RF scale scores, held for two consecutive assessments or death within 28 days, whichever occurs first. EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical,emotional,role,cognitive&social), 3 symptom scales (fatigue,nausea&vomiting,pain), global health/quality of life (GHS/QoL)&6 single items (dyspnea,insomnia,appetite loss,constipation,diarrhea&financial difficulties). PF scale has 5 questions about participants physical functioning&daily activities. RF scale has 2 questions about work/daily activities&hobbies/leisurely activities. PF&RF are scored on a 4-point scale (1=Not at All to 4=Very Much). Obtained scores are linearly transformed to score range of 0-100, where higher scores indicate a higher response level (better PF)&better functioning/support.
Time frame: Up to approximately 5.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to Function Deterioration Per European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Physical Function (PF) Scale and Role Function (RF) Scale in PTEN-loss Population | 15.7 months |
| Ipat + Abi | Time to Function Deterioration Per European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Physical Function (PF) Scale and Role Function (RF) Scale in PTEN-loss Population | 12.5 months |
p-value: 0.319895% CI: [0.89, 1.45]Log Rank
Secondary
Time to Initiation of Cytotoxic Chemotherapy for PC in ITT Population
Time to initiation of cytotoxic chemotherapy was defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for PC. KM estimates were used to determine the median time to initiation of cytotoxic chemotherapy.
Time frame: Up to approximately 5.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to Initiation of Cytotoxic Chemotherapy for PC in ITT Population | 35.5 months |
| Ipat + Abi | Time to Initiation of Cytotoxic Chemotherapy for PC in ITT Population | 40.4 months |
p-value: 0.041995% CI: [0.69, 0.99]Log Rank
Secondary
Time to Initiation of Cytotoxic Chemotherapy for Prostate Cancer (PC) in PTEN-loss Population
Time to initiation of cytotoxic chemotherapy was defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for PC. KM estimates were used to determine the median time to initiation of cytotoxic chemotherapy.
Time frame: Up to approximately 5.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to Initiation of Cytotoxic Chemotherapy for Prostate Cancer (PC) in PTEN-loss Population | 33.6 months |
| Ipat + Abi | Time to Initiation of Cytotoxic Chemotherapy for Prostate Cancer (PC) in PTEN-loss Population | 36.3 months |
p-value: 0.156695% CI: [0.65, 1.07]Log Rank
Secondary
Time to Pain Progression in ITT Population
Time to pain progression was defined as the time from randomization to the first occurrence of confirmed clinically meaningful cancer-related pain progression event. Cancer-related pain progression refers to pain onset for participants who were asymptomatic at baseline or pain worsening for those who were mildly symptomatic at baseline. Pain severity was graded on a 10-point NRS, with 0=no pain and 10=severe pain. Pain severity progression was defined as a ≥ 2-point absolute increase from baseline. KM estimates were used to determine the median time to pain progression.
Time frame: Up to approximately 5.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to Pain Progression in ITT Population | 21.9 months |
| Ipat + Abi | Time to Pain Progression in ITT Population | 25.9 months |
p-value: 0.172395% CI: [0.72, 1.06]Log Rank
Secondary
Time to Pain Progression in PTEN-loss Population
Time to pain progression was defined as the time from randomization to the first occurrence of confirmed clinically meaningful cancer-related pain progression event. Cancer-related pain progression refers to pain onset for participants who were asymptomatic at baseline or pain worsening for those who were mildly symptomatic at baseline. Pain severity was graded on a 10-point numeric rating scale \[NRS\], with 0=no pain and 10=severe pain. Pain severity progression was defined as a ≥ 2-point absolute increase from baseline. KM estimates were used to determine the median time to pain progression.
Time frame: Up to approximately 5.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to Pain Progression in PTEN-loss Population | 17.6 months |
| Ipat + Abi | Time to Pain Progression in PTEN-loss Population | 25.8 months |
p-value: 0.60195% CI: [0.58, 1.01]Log Rank
Secondary
Time to Prostate-specific Antigen (PSA) Progression, Per the PCWG3 Criteria in PTEN-loss Population
Time to PSA progression was defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression was defined as a PSA increase that was ≥ 25% and ≥ 2 nanograms per milliliters (ng/mL) above the baseline or the nadir, which was confirmed by a second value ≥ 3 weeks later. KM estimate was used to determine the median time to PSA.
Time frame: Up to approximately 5.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to Prostate-specific Antigen (PSA) Progression, Per the PCWG3 Criteria in PTEN-loss Population | 7.6 months |
| Ipat + Abi | Time to Prostate-specific Antigen (PSA) Progression, Per the PCWG3 Criteria in PTEN-loss Population | 12.6 months |
p-value: 0.004595% CI: [0.59, 0.91]Log Rank
Secondary
Time to PSA Progression, Per the PCWG3 Criteria in ITT Population
Time to PSA progression was defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression was defined as a PSA increase that was ≥ 25% and ≥ 2 ng/mL above the baseline or the nadir, which was confirmed by a second value ≥ 3 weeks later. KM estimate was used to determine the median time to PSA.
Time frame: Up to approximately 5.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to PSA Progression, Per the PCWG3 Criteria in ITT Population | 8.3 months |
| Ipat + Abi | Time to PSA Progression, Per the PCWG3 Criteria in ITT Population | 12.6 months |
p-value: <0.000195% CI: [0.61, 0.83]Log Rank
Secondary
Time to SSE in ITT Population
Time to SSE was defined as the time from randomization to the first occurrence of an SSE. A SSE was defined using one of the following: use of external-beam radiotherapy to relieve skeletal symptoms (including initiation of radium-223 to treat symptoms of bone metastases); occurrence of a new symptomatic pathological bone fracture (vertebral or non-vertebral); clinically apparent occurrence of spinal cord compression, or a tumor-related orthopedic surgical intervention. KM estimates were used to determine the median time to SSE.
Time frame: Up to approximately 5.5 years
Population: ITT population included all randomized participants, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to SSE in ITT Population | NA months |
| Ipat + Abi | Time to SSE in ITT Population | NA months |
p-value: 0.601895% CI: [0.66, 1.27]Log Rank
Secondary
Time to Symptomatic Skeletal Event (SSE) in PTEN-loss Population
Time to SSE was defined as the time from randomization to the first occurrence of an SSE. A SSE was defined using one of the following: use of external-beam radiotherapy to relieve skeletal symptoms (including initiation of radium-223 to treat symptoms of bone metastases); occurrence of a new symptomatic pathological bone fracture (vertebral or non-vertebral); clinically apparent occurrence of spinal cord compression, or a tumor-related orthopedic surgical intervention. KM estimates were used to determine the median time to SSE.
Time frame: Up to approximately 5.5 years
Population: PTEN loss population included all randomized participants with PTEN loss tumors by IHC, regardless of whether or not the participant received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pbo + Abi | Time to Symptomatic Skeletal Event (SSE) in PTEN-loss Population | NA months |
| Ipat + Abi | Time to Symptomatic Skeletal Event (SSE) in PTEN-loss Population | NA months |
p-value: 0.823995% CI: [0.61, 1.48]Log Rank