Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Immune System Diseases

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Central Nervous System Depressants

Other Dietary Supplements

Androgens

Hormones

Prolactin Release-Inhibiting Factors

Benzocaine

Hormone Antagonists

Tannic Acid

Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.

Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment."

Participants who received placebo in double-blind phase and remaind on study treatment until confirmed radiographic disease progression received enzalutamide and continued ADT in open-label phase. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.

Enzalutamide

Placebo

All participants were required to maintain ADT during study treatment, either using luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or having a history of bilateral orchiectomy.

Androgen deprivation therapy (ADT)

Medical Science Manager

The purpose of this study was to evaluate the efficacy and safety of enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT in Chinese subjects with metastatic hormone sensitive prostate cancer (mHSPC). The study was conducted in two phases: Double-Blind treatment phase and open-label phase.

An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

China ARCHES: A Multicenter, Phase 3, Randomized, Double-blind, Placebo Controlled Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Time to PSA progression was calculated as the time from the date of randomization to the first observation of PSA progression. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 microgram/liter (μg/L) (2 nanogram/milliliter \[ng/mL\]) above the nadir (i.e., lowest PSA value observed post baseline or at baseline), which was confirmed by a second consecutive value at least 3 weeks later. Time to event analysis was performed using Kaplan-Meier estimates.

An rPFS event was defined as the time from randomization to the first objective evidence of radiographic disease progression assessed by investigator or death (defined as death from any cause within 24 weeks from study drug discontinuation), whichever occurred first. Radiographic disease progression was defined as progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan. Time to event analysis was performed using Kaplan-Meier estimates.

Time to first SSE was defined as the time from randomization to the occurrence of the first SSE. SSE was defined as radiation or surgery to bone, clinically apparent pathological bone fracture or spinal cord compression. Time to event analysis was performed using Kaplan-Meier estimates.

Castration resistance was defined as occurrence of radiographic disease progression, PSA progression or SSE with castrate levels of testosterone (\< 50 ng/dL). Time to castration resistance was defined as the time from randomization to the first castration resistant event (radiographic disease progression, PSA progression or SSE), whichever occurred first. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 μg/L (2 ng/mL) above the nadir (i.e., lowest PSA value observed post baseline or at baseline), which was confirmed by a second consecutive value at least 3 weeks later. Radiographic disease progression was defined as progressive disease by RECIST version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan. SSE was defined as radiation or surgery to bone, clinically apparent pathological bone fracture or spinal cord compression. Time to event analysis was performed using Kaplan-Meier estimates.

The PSA response rate ≥50% is defined as the percentage of participants in the analysis population with maximal PSA declines of at least 50% at any time and at each visit for participants with detectable PSA at baseline and at least 1 post-baseline assessment.

The PSA response rate ≥90% is defined as the percentage of participants in the analysis population with maximal PSA declines of at least 90% at any time and at each visit for participants with detectable PSA at baseline and at least 1 post-baseline assessment.

Time to initiate of a new antineoplastic therapy (including cytotoxic and hormone therapies) was defined as the time interval from randomization to the date of the first dose administration of the first antineoplastic therapy. Time to event analysis was performed using Kaplan-Meier estimates.

The PSA undetectable rate was defined as the percentage of participants with detectable (≥ 0.2 ng/mL) PSA at baseline, which became undetectable (\< 0.2 ng/mL) during study treatment. Only participants with detectable PSA at baseline was included in the analysis.

The ORR was defined as the percentage of participants with measurable disease at baseline who achieved a complete or partial response (CR or PR) in their soft tissue disease using the RECIST version 1.1 criteria, CR was defined as complete disappearance of all target lesions and non-target disease. No new lesions. PR was defined as \>=30% decrease on study under baseline of the sum of longest diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions.

Astellas Pharma China, Inc.

The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).

Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase)

Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.

Placebo Plus ADT (Double Blind Phase)

Enzalutamide Plus ADT (Open-Label Phase)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Prior Docetaxel Use (yes or no)

High

Volume of Disease (Low Vs High)

The Intent-to-Treat (ITT) population included all participants who were randomized in the study.

Clinical Transparency

Time to Prostrate Specific Antigen (PSA) Progression

Radiographic Progression-Free Survival (rPFS)

Time to First Symptomatic Skeletal Event (SSE)

Time to Castration Resistance

Percentage of Participants With PSA Response (≥ 50%)

Percentage of Participants With PSA Response (≥ 90%)

Time to Initiation of New Antineoplastic Therapy

ITT Population with detectable PSA at baseline

Percentage of Participants With Undetectable PSA (< 0.2 ng/mL)

ITT Population with measurable soft tissue disease at baseline

Objective Response Rate (ORR)

Double Blind Phase

Open Label Phase

Symptoms and General Pathology

Rare Diseases

Disease Progression

Kennedy Disease

Gallium 68 PSMA-11

Pluvicto

Radiopharmaceuticals

Participant will receive 7.4 GBq (+/- 10%) 177Lu-PSMA-617, once every 6 weeks (+/- 1 week) for a planned 6 cycles, in addition to the Standard of Care (SOC); ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

For participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

administered intravenously once every 6 weeks (1 cycle) for 6 cycles

177Lu-PSMA-617

Intravenous dose of approx. 150 Megabecquerel (MBq) at screening and at time of centrally confirmed rPD

68Ga-PSMA-11

Administered orally on a continuous basis as per package insert and guideline

ARDT

ADT are administered as per physician order

Novartis Pharmaceuticals

The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with mHSPC. In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study. As of 31-Jan-2024, 1144 participants have been enrolled in 20 countries.

In this international, open-label, prospective, phase III study, where approximately 1126 patients with treatment naïve or minimally treated PSMA-positive mHSPC will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

The primary objective of the study is to determine whether the combination of 177Lu-PSMA-617 + SoC improves rPFS over that obtained by administration of SoC alone in mHSPC patients.

The randomization will be stratified according to the following three factors: disease volume (high v low), age \>= 70 years (yes/no), and on Previous or planned treatment (prostatectomy or radiation) to primary (prostate) tumor (yes/no).

Study duration: approximately 50 months. screening period: after signing ICF, patients will be assessed for eligibility and will be scanned with 68Ga PSMA-11 to identify PSMA expression status. Following completion of all required screening procedures and verifying participant eligibility, the participant will be randomized via the interactive response technology (IRT) system.

Amended protocol v02 included an option for participants to be enrolled into a separate long-term safety follow-up study, and China extension cohort (40 to 60 participants). Amended protocol v03 excluded China extension cohort and added a second 68Ga-PSMA-11 PET/CT scan at rPD.

Prior treatment:

* Up to 45 days of LHRH agonist/antagonists is allowed prior to ICF signature. If patient did not start the ADT prior randomization, ADT should start as soon as possible and ideally no later than 2 weeks after randomization.
* Up to 45 days of ARDT is allowed prior ICF signature. If patient did not start the ARDT prior randomization, ARDT should start as soon as possible and ideally no later than 2 weeks after randomization. Patients will received ARDT as per label instructions.

Randomization period:

The participant will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

Treatment period:

Patients randomized to the investigational arm (i.e. SoC+177Lu-PSMA-617): Patients will receive SoC as per label instructions, after randomization, if not started earlier and in the time frame allowed by the protocol. Patients must begin 177Lu-PSMA-617 dosing within 14 days after randomization or as soon as possible after the product is received. 177Lu-PSMA-617 is administered at the dose of 7.4 GBq (+/- 10%), once every 6 weeks (+/- 1 week) for a planned 6 cycles.

Patients randomized to the control arm will begin receiving SoC as per label instructions after randomization, if not started earlier and in the time frame allowed by the protocol.

The primary endpoint of rPFS will be assessed by a centralized blinded image review committee (i.e., BIRC) using radiographic images provided by the treating physician.

Participants from both arms will also undergo PET/CT scan with 68GaPSMA-11 following Centrally confirmed rPD.

An end of treatment (EOT) visit will be performed when participants permanently discontinue study treatment.

Cross-over period:

After patients randomized to the SoC alone (i.e., control) arm experience radiographic progression (the rPFS event) as confirmed by BIRC, they will be allowed to cross-over to receive 177Lu-PSMA-617 +/- SoC per the discretion of the treating physician. If cross-over to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as participants who were initially randomized to receive 177Lu-PSMA-617 as described above. Study cross-over participants for whom 177Lu-PSMA-617 is discontinued must have a second End of Treatment (EOT2) visit performed =\< 7 days and enter the Post-treatment Follow-up .

Post-Treatment Follow-Up (Safety, Efficacy):

After treatment discontinuation, all participants will be followed for safety with a 30-day safety follow-up visit (FUP) as well as longer term safety follow-up assessments for a period of approximately 12 months.

Participants who discontinue study treatment without having progressive disease confirmed by BIRC, will continue to be assessed for efficacy (efficacy follow-up) during the post-treatment follow-up period until the occurrence of their BIRC-confirmed radiographic disease progression (rPFS) event , or if the total number of protocol-defined rPFS events has occurred triggering the primary analysis, whichever occurs first.

Survival Follow-Up:

After study treatment discontinuation, or post-treatment follow-up period discontinuation, the participant's status will be collected every 90 days (via phone calls) as part of the survival follow-up. Every effort should be made to comply with the survival follow-up schedule and ensure collection of participant survival. The survival follow-up and the study will end when the number of OS events required for final OS analysis will be reached.

Patient randomized to SOC arm have an option to crossover to 177Lu-PSMA-617 treatment after rPFS

An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC

An Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care, Versus Standard of Care Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

rPFS is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1 as assessed by blinded independent central review, or death

OS is defined as time to death for any cause

PSA90 response is defined as the proportion of patients who have a more/equal 90% decrease in PSA from baseline, it will be calculated at 12, 24 and 48 months

Time to development of mCRPC is defined as the time from date of randomization to disease progression despite androgen deprivation therapy (ADT) presenting as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre existing disease, and/or the appearance of new metastases.

PFS is defined as the time from date of randomization to the date of first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first

PFS2 is defined as time from date of randomization to the first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) on next-line therapy or death from any cause, whichever occurs first.

Proportion of patients with PSA \< 0.2 ng/mL at months 12, 24 and 48 months

TTSTP is defined as time from randomization to radiographic soft tissue progression per PCWG3-modified RECIST v1.1 (Soft Tissue Rules of Prostate Cancer Working Group modified Response Evaluation Criteria in Solid Tumors Version 1.1) as assessed by Blinded Independent Central Review (BICR)

Time to SSE (TTSSE) is defined as date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first

ORR is defined as the proportion of participants with best overall response of complete response or partial response in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

DCR is defined as the proportion of participants with best overall response of complete response or partial response or Stable disease in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

DOR is defined as the duration of time between the date of first documented response (CR or PR) in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1, and the date of first documented progression or death due to any cause

TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR).

FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT-General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.

EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3=moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.

The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 \[no pain\] to 10 \[pain as bad as you can imagine\]). Pain severity progression is defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.

The distribution of adverse events (AE) will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)	NCT04076059	Metastatic Horm...	Enzalutamide Placebo Androgen depriv...	18 Years -	Astellas Pharma Inc
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC	NCT04720157	Prostatic Neopl...	177Lu-PSMA-617 68Ga-PSMA-11 ARDT ADT	18 Years -	Novartis
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC	NCT04720157	Prostatic Neopl...	177Lu-PSMA-617 68Ga-PSMA-11 ARDT ADT	18 Years -	Novartis
An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)	NCT04076059	Metastatic Horm...	Enzalutamide Placebo Androgen depriv...	18 Years -	Astellas Pharma Inc

Spots Global Cancer Trial Database for metastatic hormone sensitive prostate cancer