Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Apalutamide · 8 trials · 9 indications
rPFS is defined as the duration from the date of randomization to the date of first documentation of confirmed radiographic progressive disease or death due to any cause, whichever occurs first. rPFS will be assessed by investigators using conventional imaging (computed tomography \[CT\]/magnetic resonance imaging \[MRI\] and 99mTc bone scans).
Severity adjusted hot flash score will be calculated from the hot flash diary which will be daily filled by the participants.
pCR is assessed by a pathology blinded independent central radiology review (BICR) as defined in the pathology charter.
MFS is defined as the time from randomization to the date of the occurrence of radiographic distant metastasis evaluated by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
Will be summarized by count and percent along with the 95% confidence interval. This will then be compared to the historical control rate of 70% using a two sample z test for proportions with a one-sided p-value threshold of 0.05.
Confirmed BCR-free rate was estimated from primary efficacy variable, time to confirmed BCR. This was measured as the interval between the date of the first dose of study drug and the date of the first occurrence of confirmed prostate specific antigen (PSA) greater than (\>) 0.2 nanogram per milliliter (ng/mL). Confirmation of the PSA value was conducted within 3 to 4 weeks, regardless of study visit and timing. Participants without confirmed PSA \> 0.2 ng/mL (including those who were lost to follow-up) were censored on their last PSA measurement date during the treatment phase of the study.
Percentage of participants maintaining testosterone level \<50 ng/dL through Day 28 were reported.
Overall response rate (ORR) was defined as the percentage of participants who achieve partial response (PR) or better according to the response evaluation criteria in solid tumors (RECIST) version1.1, including with either confirmed best overall response of complete response (CR) or PR during the study. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR is defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C (last)/ lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
AUC(0-last) is defined as the time 0 to the time of the last measurable (non-below quantification limit) concentration of apalutamide calculated by linear-linear trapezoidal summation.
Cmax is defined as peak observed plasma concentration of the drug.
Cmax is the maximum observed plasma concentration.
AUC(0-72h) is area under plasma concentration-time curve from time zero to 72 hours.
AUC(0-168h) is area under plasma concentration-time curve from time zero to 168 hours.
Plasma concentration of apalutamide will be reported.
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
| Arm | Type | Description |
|---|---|---|
| Arm A (Intermittent ADT Group) | EXPERIMENTAL | Participants with PSA level \<0.2 ng/mL after 6 months of treatment with Apalutamide and ADT during initial treatment phase, will enter main treatment phase and treated with apalutamide with intermittent ADT per protocol or followed up for at least 18 months from Day 1 of Cycle 7 (each cycle 28 days) and followed up for up to a maximum of 2 years after the main treatment phase, or until death, withdrawal of consent, loss to follow-up, early termination of the study by the sponsor for any reason, whichever occurs first. |
| Arm B (Continuous ADT Group) | ACTIVE_COMPARATOR | Participants with PSA level \<0.2 ng/mL after 6 months of treatment with Apalutamide and ADT during initial treatment phase, will enter main treatment phase and continue to receive apalutamide plus ADT or followed up for at least 18 months from Day 1 of Cycle 7 (each cycle 28 days) and followed up for up to a maximum of 2 years after the main treatment phase, or until death, withdrawal of consent, loss to follow-up, early termination of the study by the sponsor for any reason, whichever occurs first. |
| Apalutamide + ADT | EXPERIMENTAL | Participants will receive androgen deprivation therapy (ADT) plus oral administration of apalutamide 240 milligram (mg) (4 tablets of 60 mg each) daily in each cycle (each cycle of 28 days). Participants will receive six cycles of treatment, followed by radical prostatectomy (RP) with pelvic lymph node dissection (pLND), followed by an additional six cycles of treatment. A Long-Term Extension (LTE) may be initiated at sponsor's discretion after completion of the primary endpoint analysis. |
| Placebo + ADT | EXPERIMENTAL | Participants will receive ADT with oral administration of matching placebo treatment daily in each cycle (each cycle of 28 days). Participants will receive six cycles of placebo treatment, followed by RP with pLND, followed by an additional six cycles of placebo treatment. A LTE may be initiated at sponsor's discretion after completion of the primary endpoint analysis. |
| Treatment (apalutamide, SBRT) | EXPERIMENTAL | Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up. |
| Apalutamide + Androgen Deprivation Therapy (ADT) | EXPERIMENTAL | In the main study, participants will receive apalutamide 240 milligram (mg) once daily orally along with ADT for 12 cycles (Each cycle is of 28 days). Participants who enrolled in the sub-study will receive apalutamide 240 mg once daily along with relugolix (a type of ADT) 120 mg once daily following a loading dose of 360 mg relugolix orally. Sub-study participants will be receiving relugolix up to Day 28 after which they will be transitioned into the main study from Cycle 2 Day 1 and will continue to receive conventional or oral ADT. |
| Apalutamide plus GnRH Agonist | EXPERIMENTAL | Participants will receive apalutamide 240 milligram (mg) in combination with a gonadotropin-releasing hormone (GnRH) agonist until disease progression, unacceptable toxicity, death, or the end of the study and each treatment cycle will be of 28 days. Participants who are benefitting from this study will enter long term extension phase. |
| Group 1: Participants with Severe Hepatic Impairment | EXPERIMENTAL | Participants with severe hepatic impairment will receive single oral dose of apalutamide on Day 1 under fasted condition. |
| Group 2: Participants with Normal Hepatic Function | EXPERIMENTAL | Participants with normal hepatic function will receive single oral dose of apalutamide on Day 1 under fasted condition. |
| Treatment Sequence AB | EXPERIMENTAL | Participants will receive a single dose of apalutamide 240 milligram (mg) (4\*60 mg tablets) swallowed whole under fasted conditions on Day 1 of Treatment Period 1 (Treatment A \[reference\]) followed by a single dose of apalutamide 240 mg (4\*60 mg tablets) as a dispersed mixture in applesauce under fasted conditions on Day 1 of Treatment Period 2 (Treatment B \[test\]). Study treatment periods will be separated by a washout interval of at least 42 days and no more than 56 days between doses. |
| Treatment Sequence BA | EXPERIMENTAL | Participants will receive a single dose of apalutamide 240 mg (4\*60 mg tablets) as a dispersed mixture in applesauce under fasted conditions on Day 1 of Treatment Period 1 (Treatment B \[test\]) followed by a single dose of apalutamide 240 mg (4\*60 mg tablets) swallowed whole under fasted conditions on Day 1 of Treatment Period 2 (Treatment A \[reference\]). Study treatment periods will be separated by a washout interval of at least 42 days and no more than 56 days between doses. |
| Apalutamide | EXPERIMENTAL | Participants will receive a single oral dose of apalutamide 240 milligram (mg) during pharmacokinetics (PK) Week Day 1 and will be monitored for one week (that is; PK Week) to assess PK and safety of drug. Subsequently, participants will further receive daily treatment of apalutamide from Cycle 1 Day 1 onwards until disease progression, withdrawal of consent, lost to follow-up, or the occurrence of unacceptable toxicity. Each treatment cycle consists of 28 days. After final analysis (FA), participants who are receiving apalutamide in the open-label treatment phase may continue receiving single oral dose apalutamide 240 mg once daily in a long-term extension (LTE) phase if they continue to derive benefit from treatment (based on investigator assessment). |
| Name | Type | Description |
|---|---|---|
| Apalutamide | DRUG | Apalutamide will be administered orally from Day 1 of Cycle 1 till 6 months in initial treatment phase and then in main treatment phase from Day 1 of Cycle 7 up to at least 18 months. |
| Androgen-deprivation Therapy (ADT) | DRUG | The choice of ADT will be at discretion of the Investigator. Dosing (dose and frequency of administration) will be consistent with the prescribing information. |
| Androgen Deprivation Therapy (ADT) | DRUG | Participants will receive a stable regimen of ADT - gonadotropin-releasing hormone analog (agonist or antagonist) (GnRHa). ADT is a kind of hormone therapy for prostate cancer. GnRHa will be administrated to achieve and maintain sub-castrate concentrations of testosterone (50 nanogram per deciliter \[ng/dL\]). |
| Placebo | DRUG | Participants will receive matching placebo oral tablets daily. |
| Biospecimen Collection | PROCEDURE | Undergo collection of blood samples |
| Computed Tomography | PROCEDURE | Undergo PSMA-PET/CT |
| Gallium Ga 68 Gozetotide | OTHER | Undergo PSMA-PET/CT |
| Guided Stereotactic Body Radiation Therapy | RADIATION | Undergo guided SBRT |
| Multiparametric Magnetic Resonance Imaging | PROCEDURE | Undergo multiparametric MRI |
| Positron Emission Tomography | PROCEDURE | Undergo PSMA-PET/CT |
| Questionnaire Administration | OTHER | Ancillary studies |
| ADT | DRUG | Participants will receive ADT intramuscular or subcutaneously during the main study. |
| Relugolix | DRUG | Participants will receive 120 mg of relugolix following a loading dose of 360 mg of (3 tablets of 120 mg each) relugolix during the sub-study. |
| GnRH Agonist | DRUG | A stable regimen of goserelin 3.6 mg will be administered as a GnRH agonist. |
Inclusion Criteria: * Diagnosis of prostate cancer prior to screening with histologically or cytologically confirmed adenocarcinoma of the prostate * For participants not undergoing Gender-affirming care: Metastatic prostate cancer disease documented by conventional imaging (example, computed tomog...