SUMMARY

• In the phase 3 TITAN study (NCT02489318) that evaluated ERLEADA compared to placebo in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving continuous androgen deprivation therapy (ADT), patients were excluded if radiation therapy (RT) was administered within 28 days of randomization. Additionally, concomitant RT for new painful metastatic prostate cancer lesions that were not present on baseline imaging was prohibited. Efficacy and safety analyses were not performed for patients who received palliative radiation to lesions at baseline in the TITAN study.^1,2
• In the phase 3 SPARTAN study (NCT01946204) that evaluated the efficacy and safety of ERLEADA compared to placebo in patients with high-risk, non-metastatic castration-resistant prostate cancer (nmCRPC) receiving continuous ADT, patients were permitted to receive salvage radiation for loco-regional pelvic disease to treat localized progression or symptoms while continuing treatment with ERLEADA.^3,4 Two patients (0.2%) and 1 patient (0.3%) in the ERLEADA and placebo groups, respectively, received concomitant RT. Efficacy and safety analyses were not performed for patients who received concomitant RT in the SPARTAN study.⁵
• ATLAS (NCT02531516) is an ongoing, phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of adding ERLEADA to gonadotropin-releasing hormone agonist (GnRHa) and external beam radiation therapy (EBRT) in patients with high-risk localized or locally advanced prostate cancer. The primary endpoint is metastasis-free survival (MFS). Efficacy and safety results have not been published.^6-8
  • A total of 90% of patients received standard EBRT to the prostate/pelvis over 68 weeks, while 10% and 6% of patients received hypofractionation and EBRT combined with brachytherapy, respectively.⁸
• PRIMORDIUM (NCT04557059) is an ongoing, phase 3, randomized, open-label, multicenter study evaluating the efficacy and safety of adding ERLEADA to RT and a luteinizing hormone-releasing hormone agonist (LHRHa) compared to RT and a LHRHa alone in patients with high-risk, prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-positive hormone-sensitive prostate cancer (HSPC). The primary endpoint is PSMA-PET metastatic progression-free survival (ppMPFS). This study also includes an observational cohort of PSMA-PET-negative patients. Efficacy and safety results have not been published.^9,10
• STARTAR (NCT03311555) was a phase 2, prospective, multicenter, single-arm, open-label study that evaluated the combined treatment of ERLEADA and ADT for 9 months with EBRT followed by 6 cycles of adjuvant docetaxel compared to the historical controls from the STREAM study in patients with prostate-specific antigen (PSA)-recurrent prostate cancer after radical prostatectomy (N=39).¹¹
  • The 2- and 3-year progression-free survival (PFS) were 84% and 71%, respectively; this improved significantly over the 3-year PFS of 47% in the historic control in the multimodality trial (P=0.004) and 54% in the STREAM treatment group (P=0.039).
  • Among patients who dose reduced or discontinued any part of study treatments, ERLEADA was held or dose reduced for 10 (25%) patients and discontinued in 2 (5%) patients. Radiation was held for 1 (3%) patient.
• FORMULA-509 (NCT03141671) is an ongoing, phase 2, randomized, open-label, multicenter study designed to evaluate the efficacy and safety outcomes of adding 6 months of ERLEADA and abiraterone acetate plus prednisone (AAP) to the standard-of-care (SOC) of 6 months of GnRHa with salvage RT in patients with unfavorable features and a detectable PSA post-RP (N=345). Patients received salvage RT plus 6 months of GnRHa and were randomized to concurrent ERLEADA 240 mg once daily (QD) plus abiraterone acetate 1000 mg plus prednisone 5 mg or bicalutamide 50 mg.¹²
  • In the ERLEADA plus AAP group vs bicalutamide group, the 3-year PFS was 74.9% vs 68.5% (HR, 0.71; 90% CI, 0.49-1.03). For baseline PSA >0.5 (HR, 0.50; 90% CI, 0.30-0.86), the 3-year PFS was 67.2% vs 46.8%.
• Metacure (NCT03436654), a phase 2, randomized, multicenter, multiarm study,¹³ tested stereotactic body radiation therapy (SBRT) +/- salvage RT to prostate bed/nodes with time-limited ADT plus androgen receptor pathway inhibitor (ARPI) hormonal blockade in patients with PSMA-PET-detected metachronous oligometastatic HSPC. Results have been reported for the B2 (n=10) and B2 expansion (n=26) cohorts.¹⁴
  • Testosterone recovery at 12 months from treatment initiation occurred in 60% (3/5) of the ERLEADA plus ADT plus AAP and 40% (2/5) of the ERLEADA plus ADT groups in cohort B2 and 54% (14/26) of the B2 expansion cohort. Of those, 100% (2/2 in ERLEADA plus ADT plus AAP and 3/3 in ERLEADA plus ADT groups) of patients in both groups of cohort B2 and 79% (11/14) of patients in the B2 expansion cohort had PSA <0.1.
• SATURN (NCT03902951), a prospective, phase 2, single-arm, single-center study, evaluated the efficacy and safety of adding ERLEADA, AAP, and PSMA-PET/computed tomography (CT)-guided metastasis-directed SBRT to intermittent ADT for patients with oligorecurrent mHSPC after prior RP (N=28). The primary endpoint was the percentage of patients with PSA <0.05 ng/mL 6 months after serum testosterone recovery to ≥150 ng/dL following androgen annihilation therapy (AAT).¹⁵
  • At 6 months after testosterone recovery, PSA was maintained at <0.05 ng/mL in 13 of 26 (50%) evaluable patients (95% CI, 32-67).
  • The rates of grade 2 and 3 AAT toxicity were 21% each.
• SOLAR (NCT03298087), a prospective, phase 2, single-arm study, evaluated the efficacy and safety of combining radical local (RP with lymph node dissection and postoperative RT or radical RT directed to the prostate, seminal vesicles, and pelvic lymph nodes) metastasis-directed SBRT, and intensified systemic therapies of limited duration (6 months on leuprolide, AAP, and ERLEADA) in veterans with de novo oligometastatic prostate cancer (N=28). The primary endpoint was the percentage of patients with undetectable serum PSA (for RP) or PSA <2 ng/mL (for radical RT) 6 months after testosterone recovery to ≥150 ng/dL.¹⁶
  • At a median follow-up of 30 months among 22 evaluable patients, 19 (86%) patients were progression-free.
  • Grade 2 and 3 toxicities, respectively, were reported in 46% and 4% of patients on primary tumor therapy; no patients on SBRT; and 42% and 4% of patients on systemic therapy. There was 1 grade 4 toxicity event.
• Interim results from an ongoing phase 2 study in patients with metachronous oligometastatic HSPC treated with ERLEADA plus ADT and SBRT (N=174)¹⁷ and an ongoing phase 2 study in patients with very high-risk, node negative prostate cancer treated with ERLEADA plus AAP plus leuprolide and ultra-hypofractionated radiation (UHRT; N=64)¹⁸ have been reported.
• Additionally, the study descriptions of ongoing phase 3 studies^19-21 and ongoing phase 2 study²² in patients treated with ERLEADA and concurrent RT have been published.
• Results from a real-world study evaluating the impact of prostate RT in patients with mHSPC receiving ERLEADA have been published (N=266).²³

Clinical Data

Phase 3 Studies

TITAN Study

Chi et al (2019)¹ evaluated the efficacy and safety of ERLEADA plus ADT compared to placebo plus ADT in patients with mCSPC (N=1052). Patients were randomized 1:1 to receive either ERLEADA 240 mg orally (PO) QD (n=525) or placebo QD (n=527). All patients in the TITAN study received a concomitant GnRH analog or had a bilateral orchiectomy (NCT02489318).

Patients were excluded if RT was administered within 28 days of randomization. Concomitant RT for new painful metastatic prostate cancer lesions that were not present on baseline imaging was prohibited. Additionally, patients discontinued ERLEADA treatment due to clinical progression, which included the need to initiate RT due to tumor progression (even in the absence of radiograph evidence of disease). Palliative radiation to lesions existing at baseline was not considered clinical progression.²

Efficacy and safety analyses were not performed for patients who received palliative radiation to lesions at baseline in the TITAN study.

SPARTAN Study

Smith et al (2018)³ study evaluated the efficacy and safety of ERLEADA in patients with nmCRPC (N=1207). Patients were randomized 2:1 to receive either ERLEADA 240 mg PO QD (n=806) or placebo QD (n=401). All patients in the SPARTAN study received a concomitant GnRH analog or had a bilateral orchiectomy. Salvage radiation for loco-regional pelvic disease to treat localized progression or symptoms was permitted while continuing treatment with ERLEADA (NCT01946204).⁴

Patient baseline demographic and disease characteristics were well balanced, and there were no significant differences between groups. The median treatment duration was 16.9 months in the ERLEADA group and 11.2 months in the placebo group.^3,5 Shown below is Table: Frequency of Concomitant Radiotherapy in the SPARTAN Study.

Efficacy and safety analyses were not performed for patients who received concomitant RT in the SPARTAN study.

Additional Information

Additional information regarding the SPARTAN study, including the clinical study report, protocol, and statistical analysis plan, can be found at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/Erleada_210951_toc.cfm (scroll to the “Sponsor Clinical Study Reports ARN-509-003 SPARTAN NCT # 01946204” section at the bottom of the web page).

ATLAS Study

ATLAS is an ongoing study evaluating the efficacy and safety of adding ERLEADA to GnRHa and EBRT in patients with high-risk localized or locally advanced prostate cancer.^6-8

Study Design/Methods

• Phase 3, randomized, double-blind, placebo-controlled, multicenter study
• A total of 1503 patients were randomized 1:1 to receive the following treatments during each 28-day treatment cycle:
  • Cycles 1-2 (neoadjuvant to RT)
    • Group 1: ERLEADA 240 mg QD, bicalutamide placebo, and GnRHa
    • Group 2: placebo, bicalutamide, and GnRHa
  • Cycles 3-4 (concurrent with RT)
    • Group 1: RT with ERLEADA 240 mg QD, bicalutamide placebo, and GnRHa
    • Group 2: RT with placebo, bicalutamide, and GnRHa
  • Cycles 5-30 (adjuvant to RT)
    • Group 1: ERLEADA 240 mg QD and GnRHa
    • Group 2: placebo and GnRHa
• Patients were stratified by Gleason score (GS), pelvic nodal status, use of brachytherapy boost, and region.
• Long-term follow-up will consist of monitoring PSA and testosterone levels every 3 months until distant metastasis by blinded independent central review (BICR), conventional imaging every 6 months until distant metastasis by BICR or death, and positron emission tomography (PET) imaging every 6 months until distant metastasis on PET or conventional imaging by BICR or death.
• The collection of PET imaging data was added to the protocol to guide treatment of patients with biochemical failure (BCF) or progressive disease after definitive RT and hormonal therapy.
• Select inclusion criteria: indicated and planned to receive primary RT for prostate cancer; histologically confirmed adenocarcinoma of an intact prostate and either GS ≥8 and ≥clinical stage T2c (≥cT2c) or GS ≥7, PSA ≥20 ng/mL and ≥cT2c; Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1; Charlson Comorbidity Index (CCI) ≤3; and adequate liver function
• Select exclusion criteria: presence of distant metastasis and history of pelvic radiation; prior treatment with GnRH analog, antiandrogen, or both for >3 months prior to randomization; prior procedural or systemic treatment for prostate cancer; cytochrome P450 17 (CYP17) inhibitors, radiopharmaceutical agents, immunotherapy, or any investigational agent; prior treatment with systemic glucocorticoids ≤4 weeks prior to randomization or is expected to require long-term use of corticosteroids during the study; and history of seizure
• Primary endpoint: MFS
• Key secondary endpoints: event-free survival (EFS), time to PSA progression, and overall survival (OS)
• Other secondary endpoints: time to next local or systemic treatment, time to distant metastasis, and MFS by conventional or PET imaging
• The safety evaluation is based on periodic physical examination, vital signs, and laboratory tests at clinic visits.
• The effect of adding ERLEADA to GnRHa on symptoms, function, and health-related quality of life (HRQoL) will be evaluated via patient-reported outcomes (PROs).

Results

Patient Characteristics

• Efficacy and safety results have not been published; however, patient baseline characteristics are available.
  • A total of 90% of patients received standard EBRT to the prostate/pelvis over 68 weeks, while 10% and 6% of patients received hypofractionation and EBRT combined with brachytherapy, respectively.⁸
  • Patient retention and physician engagement strategies were initiated during the coronavirus disease 2019 (COVID-19) pandemic, and a 96% patient retention rate was observed.²⁴

PRIMORDIUM Study

PRIMORDIUM is an ongoing study evaluating the efficacy and safety of adding ERLEADA to RT and a LHRHa compared to RT and a LHRHa alone in high-risk patients with PSMA-PET-positive HSPC. Patients who are PSMA-PET-negative at baseline will be enrolled into the observational cohort.^9,10

Study Design/Methods

• Phase 3, randomized, open-label, multicenter, global study
• A total of ~412 PSMA-PET-positive patients to achieve ~192 events and ~200 PSMA-PET-negative patients will be included in the interventional and observational cohorts, respectively. This study is not designed to compare results across cohorts.
• The treatments in the interventional cohort are randomized 1:1 as described in the Table: Treatments in the Interventional Cohort.
• Patients who are PSMA-PET-negative and enrolled in the observational cohort will receive SOC treatment per local practice and will have data collected during routine clinical practice which will include therapies administered, clinical evaluations, disease progression assessments, and survival until closure of the interventional cohort.

Treatments in the Interventional Cohort^9,10,a

• Patients in the interventional cohort will be stratified by location of PSMA-PET-positive lesions, PSA doubling-time (PSADT), and planned use of SBRT.
  • At sites where it is a standard approach, SBRT may be used for ≤3 PSMA-avid distant metastases; the decision to use SBRT must be made before randomization.
• In the interventional cohort, PSA will be measured every 3 months until the primary endpoint. If the PSA remains <0.2 ng/mL, PSMA-PET is assessed by BICR at 6 and 12 months, then annually until PSMA-PET progression. If PSA rises to ≥0.2 ng/mL, PSMA-PET is done immediately then every 6 months until PSMA-PET progression. Testosterone and patient-reported outcomes (PROs) will additionally be assessed.
  • Post-PSMA-PET-progression assessments will include bone scans, CT/magnetic resonance imaging (MRI), and PROs.
• Select inclusion criteria: histologically confirmed adenocarcinoma of the prostate; previously treated with RP with or without lymph node dissection and either any post-operative PSA of <0.1 ng/mL within 12 months after RP and without any PSA ≥0.1 ng/mL within the 4- to 8-week period after RP for biochemical recurrence after RP or PSA ≥0.1 ng/mL within the 4- to 8-week period after RP for persistent PSA after RP, confirmed by additional measurement ≥3 weeks later; biochemically recurrent prostate cancer after RP with high risk of developing metastasis defined as pathological GS ≥8 or PSADT ≤12 months; no evidence of metastases on screening CT/MRI of the chest/abdomen/pelvis, and technetium-99m (^99mTc) whole-body bone scan; ECOG PS 0 or 1; results of PSMA-PET at screening as determined by BICR had to be:
  • PSMA-PET-negative for any prostate cancer lesions (ie, no locoregional lesion and no distant lesions)
  • PSMA-PET-positive for ≥1 locoregional (pelvic) lesion without distant extra pelvic lesion
  • PSMA-PET-positive for ≥1 loco-regional (pelvic) lesion with extra pelvic lesion(s)
• Select exclusion criteria: history of pelvic radiation for malignancy; history of ADT or chemotherapy for prostate cancer; prior treatment for biochemical recurrence; prior treatment with a CYP17 inhibitor, androgen receptor (AR) antagonist, medication that lowers androgen levels, or bilateral orchiectomy; small cell or neuroendocrine carcinoma of the prostate; clinically significant cardiovascular disease; use of 5-alpha-reductase inhibitor or an investigational agent ≤4 weeks prior to randomization; history of seizure or at increased risk of seizure
• Primary endpoint: ppMPFS, defined as the appearance of at least 1 new PSMA-PET-positive distant lesion compared with the previous scan assessed by BICR, or death
• Secondary endpoints: time to PSA progression; PSA response rate; PSA levels at end of week 26; time to locoregional progression by PSMA-PET; overall survival (OS); prostate cancer-specific survival; and adverse events (AEs)

Results

• Efficacy and safety results have not been published.
• Baseline characteristics of patients enrolled in both cohorts through the data cutoff date of January 12, 2023 have been published.²⁵

Phase 2 Studies

STARTAR Study

STARTAR¹¹ was a phase 2 study that evaluated combined treatment of ERLEADA and ADT for 9 months with EBRT followed by 6 cycles of adjuvant docetaxel compared to the historical controls from the STREAM study in patients with PSA-recurrent prostate cancer after radical prostatectomy (N=39).

Study Design/Methods

• Phase 2, prospective, multicenter, single-arm, open-label study
• Patients received ADT for over 9 months and ERLEADA 240 mg orally daily for approximately 36 weeks.
• Beginning at week 8, EBRT at 64.8-68 Gy was administered to the prostate bed over 68 weeks, followed by a 4-week washout and then docetaxel 75 mg/m² intravenously every 3 weeks for up to 6 cycles.
• Primary endpoint: 36-month PSA PFS
• Secondary endpoints: proportion of patients at 12, 24, and 36 months with PSA levels of <0.1 ng/mL and testosterone recovery to >100 ng/dL, biochemical (PSA) PFS over time, PSA nadir, time to testosterone recovery, safety, and percentage of patients completing all treatments

Results

Baseline Characteristics

• The median age in the overall population and the STREAM cohort (N=38) was 64 years (IQR, 60-67 and IQR, 59-69, respectively).
• The median baseline PSA in the overall population and the STREAM cohort was 0.58 ng/mL (IQR, 0.35-1.06) and 0.4 ng/mL (0.29-0.75), respectively.
• All the patients in the STARTAR cohort completed the planned radiation treatment course. A higher rate of patients with N1 disease (6/9 [67%] with N1, 5/28 [18%] with N0, and none with Nx) underwent pelvic radiation.

Efficacy

• The median follow-up time for patients without progression was 37 months (IQR, 36-38).
• All patients who were evaluable for the primary endpoint were alive at the time of analysis, and all the patients (100%) achieved undetectable PSA as PSA nadir on treatment.
• The 2- and 3-year PFS were 84% and 71%, respectively; this improved significantly over the 3-year PFS of 47% in the historic control in the multimodality trial and 54% in the STREAM treatment cohort (P=0.004 and P=0.039, respectively).
• Testosterone recovery was reported in 4 (11%), 31 (82%), and all 37 patients at 1 year, 2 years, and data lock, respectively.
• PSA of <0.1 ng/mL with testosterone recovery was reported in 38%, 67%, and 69% of patients at 1, 2, and 3 years, respectively.
• The median time to testosterone recovery was 15 months (95% CI, 13-17).

Safety

• The most common AEs (>30%) included hot flashes (97%), fatigue (87%), alopecia (77%), anemia (59%), dysgeusia (59%), maculopapular rash (54%), diarrhea (44%), urinary frequency (44%), nausea (41%), insomnia (38%), urinary urgency (36%), paresthesia (36%), dyspnea (33%), pruritus (31%), and edema (31%).
• The maximum hematologic grade 3-4 AEs were neutropenia (27 [69%]), including 3 febrile neutropenia events during chemotherapy.
• Serious AEs observed included febrile neutropenia (3 [8%]) and 1 (2.6%) each of flu-like symptoms/sinus tachycardia, fever, pelvic infection, hematoma, and thromboembolism.
• Among patients who dose reduced or discontinued any part of study treatments, ERLEADA was held or dose reduced for 10 (25%) patients, with 2 (5%) patients discontinuing, and radiation was held for 1 (3%) patient.

FORMULA-509 Study

Nguyen et al (2023)¹² evaluated the efficacy and safety outcomes of adding 6 months of ERLEADA and AAP to the SOC of 6 months of GnRHa with salvage RT in patients with unfavorable features and a detectable PSA post-RP (N=345).

Study Design/Methods

• Phase 2, randomized, open-label, multicenter study
• Patients received salvage RT plus 6 months of GnRHa and randomization was to concurrent ERLEADA 240 mg QD plus abiraterone acetate 1000 mg plus prednisone 5 mg or bicalutamide 50 mg. Radiation to pelvic nodes was required for pN1 and optional for pN0.
• Patients were stratified by PSA at study entry (>0.5 vs ≤0.5) and pN0 vs pN1.
• Select inclusion criteria: PSA ≥0.1 post-RP and ≥1 unfavorable features: Gleason 8-10, PSA >0.5, pT3/T4, pN1 or radiographic N1, PSADT <10 months, negative margins, persistent PSA, gross local/regional disease, or high risk on Decipher test)
• Primary endpoint: PSA PFS
• Secondary endpoint: MFS, determined by conventional imaging

Results

Patient Characteristics

• Twenty-nine percent of patients were pN1 and 31% of patients had PSA>0.5 ng/mL.

Efficacy

• Results are summarized in Table: Primary and Secondary Endpoint Results.
• The median follow-up was 34 months.
• In a pre-planned analysis by stratification factors, the ERLEADA plus AAP group was superior to the bicalutamide group for PSA >0.5 for PFS (HR, 0.50; 90% CI, 0.30-0.86; 2-sided P-value=0.03 and 3 year PFS 67.2% vs 46.8%) and MFS (HR, 0.32; 90% CI, 0.15-0.72; 2-sided P-value=0.01 and 3 year MFS 84.3% vs 66.1%).

HRQoL Outcomes

• Patient-reported HRQoL was also evaluated using validated questionnaires at baseline, end of treatment, and 1 year after treatment. Both treatment arms demonstrated clinically meaningful declines in EPIC-26 hormonal domain (median change, -15 bicalutamide group, -15 ERLEADA plus AAP group) and increases in PROMIS Fatigue (median change, 6 bicalutamide group, 7.4 ERLEADA plus AAP group) from baseline to end of treatment, which improved to near baseline at 1 year after treatment for both groups.²⁶
• Median Saint Louis University Mental Status Exam (SLUMS) score was within normal range at baseline, end of treatment, and 1 year after treatment for both groups.²⁶
• There was no significant difference in patient-reported hormonal function, fatigue, or mental status between groups at end of treatment and 1 year after treatment.²⁶

Safety

• AEs were consistent with the known safety profiles of each medication, with more rash and hypertension reported in the ERLEADA plus AAP group (incidence not reported).

Metacure Study

Bent et al (2025)¹⁴ reported results from the B2 (n=10) and B2 expansion (n=26) cohorts in patients with PSMA-PET-detected metachronous oligometastatic HSPC.

Study Design/Methods

• Phase 2, randomized, multicenter, multiarm study
• The B2 and B2 expansion cohorts tested SBRT +/- salvage RT to prostate bed/nodes with time-limited ADT plus ARPI hormonal blockade.
  • Cohort B2 randomized patients to metastasis-directed SBRT with either 10 months of ERLEADA plus ADT plus AAP or ERLEADA plus ADT.
  • In the B2 expansion cohort, patients received 6 months of ERLEADA plus ADT with SBRT.
• Inclusion criteria: biochemical recurrence (BCR) or persistence (PSA >0.2) after prostatectomy with metastases treatable within a maximum of 3 RT plans
• Primary endpoint: proportion of patients with undetectable PSA (PSA <0.1) at 12 months from treatment initiation in patients with recovered testosterone
• Secondary endpoints: PSA <0.1 at 24 months, time to PSA progression, time to testosterone recovery (>150 ng/dL), radiographic PFS, PFS.

Results

Efficacy

• In the B2 and B2 expansion cohorts, the median follow-up was 35 months and 19 months, respectively.
• Testosterone recovery at 12 months from treatment initiation occurred in 60% (3/5) of the ERLEADA plus ADT plus AAP and 40% (2/5) of the ERLEADA plus ADT groups in cohort B2 and 54% (14/26) of the B2 expansion cohort.
  • Of those, 100% (2/2 in ERLEADA plus ADT plus AAP and 3/3 in ERLEADA plus ADT groups) of patients in both groups of cohort B2 and 79% (11/14) of patients in the B2 expansion cohort had PSA <0.1.
• Median time to PSA progression and PFS was 26 months for the ERLEADA plus ADT plus AAP group of cohort B2 and not reached for the other group of cohort B2 or B2 expansion cohort.
• Median rPFS was not reached in any group.
• At 12 months, all patients in the B2 and B2 expansion cohorts were progression free.
• At 18 months, PFS was 100% for the ERLEADA plus ADT group and 60% for the ERLEADA plus ADT plus AAP group of cohort B2 and 85% for the B2 expansion cohort.
• At 24 months, PFS was 60% for the ERLEADA plus ADT group and 60% for the ERLEADA plus ADT plus AAP group of cohort B2.
• Median testosterone recovery was 3.0 and 5.5 months for the B2 and B2 expansion cohorts, respectively.

Safety

• Grade 3 treatment-related AEs were seen in no B2 and 1 (lymphopenia) B2 expansion patient, respectively.

Francolini et al (2025)¹⁷ reported interim results of a phase 2 study in patients with metachronous oligometastatic HSPC treated with ERLEADA plus ADT and SBRT (N=174).

Study Design/Methods

• Phase 2, randomized study
• Patients were randomized into 2 groups:
  • Arm A (Control): SOC with ERLEADA plus ADT
  • Arm B (Treatment): ERLEADA plus ADT with SBRT on all sites of metastatic disease
• Exclusion criteria: patients with de novo metastatic disease or with >5 distant metastases
• Primary endpoint: complete biochemical response defined as PSA <0.2 ng/mL²⁷

Results

Efficacy

• Of patients enrolled thus far, 87/174 reached a minimum follow-up of 3 months.
• After 3 months of treatment initiation with ERLEADA plus ADT, a total of 92.9% of patients in the treatment group achieved a complete biochemical response compared to 91.1% of patients in the control group (OR, 1.27; 95% CI, 0.27-6.03; P=0.765).
• Patients with PSMA-positive lesions undetected on conventional imaging had similar outcomes to those with consistent target lesions identified on both conventional and PSMA imaging (OR, 0.74; 95% CI, 0.08-6.94; P=0.791).
• The rate of complete biochemical response was not influenced by the presence of bone metastatic lesions (OR, 1.39; 95% CI, 0.29-6.67; P=0.678).
• After adjusting for the number of lesions, a significant clinical benefit was observed in patients with <3 metastatic sites in the treatment group (OR, 5.88; 95% CI, 1.13-33.3; P=0.03).

Safety

• Safety results were not reported.

McBride et al (2021)¹⁸ reported interim results of an ongoing phase 2 study in very high-risk patients with node negative prostate cancer treated with ERLEADA plus AAP plus leuprolide in conjunction with UHRT (N=64).²⁸

Study Design/Methods

• Phase 2, open-label, single arm study
• Patients received treatment for 6 months with ERLEADA in combination with¹⁸:
  • AAP plus
  • Leuprolide and UHRT 7.5-8 Gy x 5 fractions
• Select inclusion criteria: very high-risk prostate cancer defined as having a GS of 9-10, or >4 cores of GS 8 disease, or 2 high-risk features (including rT3/T4 disease)
• Select exclusion criteria: radiographic evidence of metastatic disease, ≥1 positive lymph node as determined by radiographic assessment of MRI or CT, severe hepatic impairment (Child-Pugh Class C), and prior treatment for prostate cancer except for patient who received LHRH agonist/antagonist therapy for ≤1 month prior to study enrollment²⁸
• Primary endpoint: BCR defined as nadir PSA + 2 ng/mL¹⁸

Results

Patient Characteristics

• The median age was 69 years old (range, 50-90) and serum PSA at baseline was 12 ng/dL (range, 3.1-209.5).
• A total of 45 patients had a GS of 9-10, 14 patients had a GS of 8, and 5 patients had a GS of 6-7.
• At diagnosis, the radiographic T stages (MRI technique) were as follows: T2, 70.3% (45/64); T3a, 18.7% (12/64); T3b, 10.9% (7/64).

Efficacy

• A total of 98.4% of patients (63/64) achieved an undetectable nadir PSA.
  • The median time to nadir PSA from start of treatment was 2 months (range, 1-9).
• The median time to achieve the post-treatment, non-castrate testosterone level (>150 ng/mL) was 6.5 months (range, 2.5-25.5).
• BCR was reported in 7 patients.
• The 2- and 3-year bRFS were 95% (95% CI, 89.7-100) and 89.7% (95% CI, 81-99.3), respectively.
• Among the 57 patients without BCR (median follow-up of 30 months), 98.2% (56/57) had a non-castrate testosterone level of >150 ng/mL at the last follow-up visit.
  • The median PSA was 0.10 ng/mL (IQR, <0.10-0.30).
    • PSA of ≤0.20 ng/mL was reported in 70.2% of patients (40/57).
    • Undetectable PSA (<0.10 ng/mL) was reported in 42.1% of patients (24/57).

Safety

• Transient grade 3 toxicities were reported in 15 patients (hypertension, n=12; rash, n=3).

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 15 May 2025.