A Comparative Dose-finding Study of RS-113 in Patients With Metastatic Castration-resistant Prostate Cancer

A Phase II, Open-label, Randomized, Comparative Dose-finding Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of RS-113 in Patients With Metastatic Castration-resistant Prostate Cancer

The primary objective of the study is to determine the therapeutic dose of RS-113 in patients with metastatic castration-resistant prostate cancer based on efficacy, safety, and pharmacokinetic parameters. The secondary objectives are to assess a pilot efficacy and safety of different doses of RS-113 versus abiraterone, as well as to investigate pharmacokinetics profile and to perform a pilot evaluation of pharmacokinetics parameters of RS-113 in patients with metastatic castration-resistant prostate cancer

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: RS-113, 160 mg; Drug: Androgen deprivation therapy (ADT); Drug: RS-113, 240 mg; Drug: RS-113, 320 mg; Drug: Abiraterone; Drug: Prednisolone

Detailed Description

This is an open-label, randomized, comparative phase II clinical trial conducted in 4 treatment arms:

• Arm 1: RS-113 160 mg (2 capsules) once daily (QD)
• Arm 2: RS-113 240 mg (3 capsules) QD
• Arm 3: RS-113 320 mg (4 capsules) QD
• Arm 4: abiraterone 1000 mg (4 tablets) QD plus prednisolone 10 mg QD

All enrolled patients who have not previously undergone a surgical castration will receive androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) analogues throughout the study

The study will include the following periods:

1. Screening period: up to 28 days Days [-27 to -0] prior to the first dose of the study treatment

2. Core study: up to 2 years Days [1 to 728]

   Eligible patients should be randomized to one of four treatment arms (in a 1:1:1:1 ratio):

   • Arm 1: RS-113 160 mg (2 capsules) QD
   • Arm 2: RS-113 240 mg (3 capsules) QD
   • Arm 3: RS-113 320 mg (4 capsules) QD
   • Arm 4: abiraterone 1000 mg (4 tablets) QD plus prednisolone 10 mg QD

   During the core study, the treatment will continue until the earliest of the following:

   • Day 728 (+7 days)
   • Disease progression (per RECIST 1.1 and PCWG3 criteria)
   • Unacceptable toxicity
   • Patient withdrawal from the study

   During the core study tumor response assessments will be performed approximately every 8 weeks for the first 24 weeks, and every 12 weeks thereafter

3. Extension phase

   Patients who had stable disease or tumor response within 2 years of treatment may be enrolled in an extension study. During the Extension phase, patients will continue to receive the same treatment regimen as assigned in the Core study

   During the Extension phase, the treatment will be administered from Day 728 until the earliest of the following:

   • Disease progression
   • Unacceptable toxicity
   • Patient withdrawal from the study

4. Follow-up period (follow-up/FU)

   • Patients who complete the planned 2-year study treatment and are not enrolled in the Extension phase will have one in-person Follow-up (FU) visit 28±3 days after the last dose of investigational product/comparator. This will be the final study visit for these patients. Subsequent treatment will be provided through the national healthcare system (as part of routine clinical practice) if indicated.
   • Patients who discontinue treatment early due to disease progression will have one in-person FU visit 28±3 days after the last dose of investigational product/comparator (for safety data collection). Thereafter, follow-up will be conducted via telephone contacts every 12 weeks until Day 728 or death (for survival data collection).
   • Patients who discontinue treatment early for reasons other than disease progression will have one in-person FU visit 28±3 days after the last dose of investigational product/comparator (for safety data collection). Subsequently, they will undergo FU visits with tumor response assessments every 8 weeks until Day 169, and then every 12 weeks until Day 728, disease progression, or initiation of new treatment, whichever occurs first

Completing the last visit means the end of participation in the clinical trial for each particular patient

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russia
  • Arkhangelsk, Russia, 163045
    • State Budgetary Healthcare Institution of the Arkhangelsk Region "Arkhangelsk Oncology Dispensary"
  • Istra, Russia, 143515
    • Moscow City Clinical Oncology Hospital No. 62 of the Moscow Department of Healthcare
  • Ivanovo, Russia, 153040
    • Ivanovo Regional Oncology Dispensary
  • Kaluga, Russia, 248007
    • Kaluga Regional Clinical Oncology Dispensary
  • Kuz'molovskiy, Russia, 191104
    • State Budgetary Healthcare Institution "Leningrad Regional Clinical Hospital"
  • Moscow, Russia, 125367
    • Federal State Autonomous Institution "National Medical Research Center 'Medical and Rehabilitation Center'" of the Ministry of Health of the Russian Federation
  • Moscow, Russia, 143442
    • Joint-Stock Company "Medsi Group of Companies"
  • Moscow, Russia, 117152
    • Oncology Center No. 1 of the City Clinical Hospital named after S.S. Yudin of the Moscow Healthcare Department
  • Moscow, Russia, 125284
    • National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
  • Moscow, Russia, 127521
    • Research Lab LLC
  • Novosibirsk, Russia, 630091
    • LLC MSCh "Klinitsist-Klinika Pretor"
  • Saint Petersburg, Russia, 195271
    • Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of Saint-Petersburg"
  • Saint Petersburg, Russia, 198255
    • City Clinical Oncology Dispensary (Saint Petersburg)
  • Tomsk, Russia, 634063
    • Siberian State Medical University
  • Tyumen, Russia, 625041
    • Multidisciplinary Clinical Medical Center "Medical City"
  • Yaroslavl, Russia, 150054
    • State Institution of Healthcare of Yaroslavl Region "Regional Oncology Hospital"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily signed and dated Informed Consent Form (ICF) of the patient agreed to take part in this Study
2. Histologically confirmed diagnosis of prostate adenocarcinoma showing no neuroendocrine, signet-ring cell, small cell, or ductal differentiation
3. Ongoing androgen deprivation therapy for prostate cancer aimed at testosterone suppression with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist at a stable dose and schedule for at least 4 weeks immediately prior to Day 1, or a history of bilateral orchiectomy (i.e., medical or surgical castration). Patients who have not undergone bilateral orchiectomy must agree to continue effective continuous LHRH analogue therapy throughout the study
4. Serum testosterone level ≤ 50 ng/dL (1.73 nmol/L)
5. Prostate-specific antigen (PSA) level > 2 ng/mL

6. Evidence of progressive disease at the time of randomization, defined by one or more of the following criteria:

   • PSA progression, defined as at least two consecutive increases in PSA levels occurring ≥ 2 weeks apart, with at least one increase documented during screening; the PSA level at screening must be ≥ 2 ng/mL
   • Soft tissue disease progression based on computed tomography (CT) or magnetic resonance imaging (MRI) assessment per RECIST v1.1
   • Bone disease progression based on bone scintigraphy findings
7. Disease progression occurring during androgen deprivation therapy or during or after docetaxel chemotherapy administered as first-line treatment for metastatic hormone-sensitive prostate cancer
8. Asymptomatic or mildly symptomatic prostate cancer, defined as a score < 4 on Question 3 of the Brief Pain Inventory-Short Form (BPI-SF)
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
10. Life expectancy ≥ 24 weeks

11. Major organ function must meet the following criteria:

    • Absolute neutrophil count (ANC) ≥ 1,500/mm^3 (1.5 × 10^9 cells/L)
    • Platelet count ≥ 100,000/mm^3 (100 × 10^9 cells/L)
    • Hemoglobin ≥ 90 g/L
    • Total bilirubin ≤ 1.5 × ULN
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN, or ≤ 3 × ULN in the presence of liver metastases
    • Serum creatinine < 1.5 × ULN or estimated glomerular filtration rate (eGFR) > 45 mL/min, calculated using CKD-EPI equations
12. Fertile male patients must agree to abstain from heterosexual intercourse or to use highly effective methods of contraception, starting from the date of signing the informed consent form, throughout the entire study treatment period, and for at least 28 days after investigational product/comparator discontinuation

Exclusion Criteria:

1. Presence of central nervous system (CNS) metastases that are progressive or associated with clinical symptoms (e.g., cerebral edema, spinal cord compression), or requiring treatment with glucocorticoids and/or anticonvulsants. Patients with brain metastases may be enrolled in case adequate treatment (surgery and/or radiotherapy) has been completed and radiographic stability has been documented for at least 4 weeks prior to the planned date of randomization. Newly diagnosed CNS metastases identified during screening that are asymptomatic and do not require treatment are not considered an exclusion criterion

2. Prior antitumor therapy:

   • Radiotherapy (except palliative irradiation of bone lesions for pain control) within 4 weeks prior to the planned date of randomization
   • Prior treatment with first-generation antiandrogens (flutamide, bicalutamide, nilutamide) within 4 weeks prior to the planned date of randomization
   • Prior treatment with second-generation antiandrogens (enzalutamide, apalutamide, darolutamide)
   • Use of bisphosphonates or denosumab is permitted only if treatment was initiated prior to the planned date of randomization

3. Clinically significant cardiovascular disease, including:

   • Myocardial infarction within 6 months prior to the planned date of randomization
   • Unstable angina within 3 months prior to the planned date of randomization
   • Chronic heart failure NYHA class III or IV
   • Clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation)
   • QTc interval > 460 ms on ECG (calculated using Fridericia formula), or long QT syndrome identified at screening
   • Left ventricular ejection fraction ≤ 50% by echocardiography
   • Hypotension (systolic blood pressure < 80 mmHg) or bradycardia (heart rate < 50 bpm), except when drug-induced (e.g., beta-blockers), at the time of the planned randomization
   • Uncontrolled arterial hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 105 mmHg) at the time of the planned randomization

4. Clinically significant CNS disorders, including:

   • History of seizures or conditions that may predispose to seizure development
   • Presence of stroke or transient ischemic attack within 12 months prior to the planned date of randomization
   • Primary brain tumors, cerebral arteriovenous malformations, meningiomas, schwannomas, or other benign CNS disorders that may require surgical or radiation treatment (patients with such conditions may be enrolled if no surgical or radiotherapy intervention is required)
   • Traumatic brain injury or loss of consciousness within 12 months prior to the planned date of randomization
5. Presence of untreated spinal cord compression or any other severe or systemic disease increasing the risk of treatment-related complications
6. Presence of clinically significant pituitary or adrenal dysfunction that cannot be adequately controlled with stable-dose hormonal or other standard therapy for at least 28 days prior to the planned date of randomization
7. History of another malignancy that is progressive or required anticancer treatment (including hormonal therapy) within 5 years prior to the planned date of randomization, except curatively treated basal cell or squamous cell carcinoma of the skin
8. History of other significant comorbid conditions that, in the investigator's opinion, may worsen during the study, including uncontrolled diabetes mellitus

9. Prior or concomitant therapy:

   • Use of medications that may induce seizures within 4 weeks prior to the planned date of randomization
   • Use of inhibitors or inducers of CYP3A4 or CYP2D6 within 4 weeks prior to the planned date of randomization
   • Use of medications classified as QT prolongation risk class I within 4 weeks prior to the planned date of randomization; QT risk class II medications are permitted if administered at a stable dose for at least 5 half-lives prior to the planned date of randomization
   • Prior or concomitant treatment with 5-alpha reductase inhibitors or anabolic steroids within 6 months prior to the planned date of randomization
   • Prior systemic glucocorticosteroid therapy at doses equivalent to ≥ 10 mg prednisone within 3 months prior to the planned date of randomization, except corticosteroids administered following brain irradiation, if treatment has been completed prior to enrollment in the study
10. History of allergic reactions, including reactions to medicinal products or food, that are clinically significant, in the opinion of the investigator
11. Presence of conditions limiting the patient's ability to comply with protocol requirements, including dementia, neurological or psychiatric disorders, substance or alcohol abuse, or religious or personal beliefs potentially limiting standard treatment during the study. Patients receiving narcotic analgesics for pain control may be enrolled.
12. Concurrent participation in another interventional clinical trial within 30 days prior to signing the informed consent form (if at least one dose of investigational product/comparator was received), or prior participation in this study (if at least one capsule of RS-113 or one tablet of abiraterone was administered by the patient)
13. Acute infectious diseases or exacerbation of chronic infections within 14 days prior to the planned date of randomization
14. Presence of current hepatitis B or C infection, evidence of HIV infection or active syphilis
15. Use of live vaccines within 30 days prior to the planned date of randomization. For patients receiving approved SARS-CoV-2 vaccines, the instructions for use and/or local requirements must be followed. Use of the Sputnik V vaccine is permitted provided that at least 7 days have elapsed between administration of the second vaccine dose and the first dose of the investigational product
16. Inability to swallow the investigational or comparator product
17. Inability to administer intravenous contrast
18. Presence of hypersensitivity (grade ≥ 3) to any component of RS-113, abiraterone, prednisone, or LHRH agonists (goserelin, leuprorelin, triptorelin, buserelin)
19. Presence of any other significant concomitant disease or condition that, in the investigator's reasonable judgment, may adversely affect the patient's participation, safety, or interpretation of study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RS-113, 160 mg + androgen deprivation therapy (ADT); RS-113 is taken once daily (QD) orally, 2 capsules at a time (160 mg), 1 hour after a meal in the morning Androgen deprivation therapy (ADT) will be administered using analogues of luteinizing hormone-releasing hormone (aLHRH): goserelin (at a dose of 3.6mg every 28 days or 10.8 mg every 84 days, subcutaneously, into the anterior abdominal wall), or; leuprorelin (7.5 mg every 28 days or 22.5 mg every 3 months, subcutaneously, into the anterior abdominal wall), or; triptorelin (3.75 mg every 28 days intramuscularly), or; buserelin (3.75 mg every 28 days, intramuscularly)	Drug: RS-113, 160 mg; Hard gelatin capsules, 80 mg; Other Names: L01069; Drug: Androgen deprivation therapy (ADT); Goserelin: subcutaneous implant, 3.6 mg or 10.8 mg, or; Leuprorelin: lyophilisate for solution for subcutaneous injection, 7.5 mg or 22.5 mg, or; Triptorelin: lyophilisate for solution for intramuscular injection, 3.75 mg, or; Buserelin: lyophilisate for solution for intramuscular injection, 3.75 mg
Experimental: RS-113, 240 mg + androgen deprivation therapy (ADT); RS-113 is taken orally QD, 3 capsules at a time (240 mg), 1 hour after a meal in the morning Androgen deprivation therapy (ADT) will be administered using analogues of luteinizing hormone-releasing hormone (aLHRH): goserelin (at a dose of 3.6mg every 28 days or 10.8 mg every 84 days, subcutaneously, into the anterior abdominal wall), or; leuprorelin (7.5 mg every 28 days or 22.5 mg every 3 months, subcutaneously, into the anterior abdominal wall), or; triptorelin (3.75 mg every 28 days intramuscularly), or; buserelin (3.75 mg every 28 days, intramuscularly)	Drug: Androgen deprivation therapy (ADT); Goserelin: subcutaneous implant, 3.6 mg or 10.8 mg, or; Leuprorelin: lyophilisate for solution for subcutaneous injection, 7.5 mg or 22.5 mg, or; Triptorelin: lyophilisate for solution for intramuscular injection, 3.75 mg, or; Buserelin: lyophilisate for solution for intramuscular injection, 3.75 mg; Drug: RS-113, 240 mg; Hard gelatin capsules, 80 mg; Other Names: L01069
Experimental: RS-113, 320 mg + androgen-deprivation therapy (ADT); RS-113 is taken orally QD, 4 capsules at a time (320 mg), 1 hour after a meal in the morning Androgen deprivation therapy (ADT) will be administered using analogues of luteinizing hormone-releasing hormone (aLHRH): goserelin (at a dose of 3.6mg every 28 days or 10.8 mg every 84 days, subcutaneously, into the anterior abdominal wall), or; leuprorelin (7.5 mg every 28 days or 22.5 mg every 3 months, subcutaneously, into the anterior abdominal wall), or; triptorelin (3.75 mg every 28 days intramuscularly), or; buserelin (3.75 mg every 28 days, intramuscularly)	Drug: Androgen deprivation therapy (ADT); Goserelin: subcutaneous implant, 3.6 mg or 10.8 mg, or; Leuprorelin: lyophilisate for solution for subcutaneous injection, 7.5 mg or 22.5 mg, or; Triptorelin: lyophilisate for solution for intramuscular injection, 3.75 mg, or; Buserelin: lyophilisate for solution for intramuscular injection, 3.75 mg; Drug: RS-113, 320 mg; Hard gelatin capsules, 80 mg; Other Names: L01069
Active Comparator: Abiraterone + prednisolone + androgen deprivation therapy (ADT); Abiraterone is taken at a dose of 1000 mg (4 tablets of 250 mg) QD, 1 hour before a meal or 2 hours after a meal in combination with prednisolone at a dose of 10 mg (2 tablets of 5 mg) QD Androgen deprivation therapy (ADT) will be administered using analogues of luteinizing hormone-releasing hormone (aLHRH): goserelin (at a dose of 3.6mg every 28 days or 10.8 mg every 84 days, subcutaneously, into the anterior abdominal wall), or; leuprorelin (7.5 mg every 28 days or 22.5 mg every 3 months, subcutaneously, into the anterior abdominal wall), or; triptorelin (3.75 mg every 28 days intramuscularly), or; buserelin (3.75 mg every 28 days, intramuscularly)	Drug: Androgen deprivation therapy (ADT); Goserelin: subcutaneous implant, 3.6 mg or 10.8 mg, or; Leuprorelin: lyophilisate for solution for subcutaneous injection, 7.5 mg or 22.5 mg, or; Triptorelin: lyophilisate for solution for intramuscular injection, 3.75 mg, or; Buserelin: lyophilisate for solution for intramuscular injection, 3.75 mg; Drug: Abiraterone; Tablets, 250 mg; Drug: Prednisolone; Tablets, 5 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-free survival (PFS) at 1 year in RS-113 treatment arms	Progression-free survival (PFS) expressed as the median PFS for a period of up to 1 year of treatment inclusive in RS-113 treatment arms (per RECIST 1.1 and PCWG3 criteria) PFS is defined as the time from randomization to disease progression per RECIST 1.1 (an ≥ 20% increase in the sum of diameters of target lesions taking as reference the smallest sum recorded during the study (with an absolute increase of sum at least 5 mm), or the appearance of ≥ 1 new lesions), or death due to any cause According to PCWG3, progression is defined as: two or more new lesions detected on the first post-baseline scan with at least 2 additional lesions on a subsequent scan; two or more new lesions detected on a subsequent scan (if one or no new lesions were seen at the first post-baseline scan) and confirmed by a follow-up scan	Up to day 337 (visit 16)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) rate (%) at 1 year in RS-113 treatment arms	Progression-free survival (PFS) expressed as the rate (%) at 1 year PFS in RS-113 treatment arms (per RECIST 1.1 and PCWG3 criteria) PFS is defined as the time from randomization to disease progression per RECIST 1.1 (an ≥ 20% increase in the sum of diameters of target lesions taking as reference the smallest sum recorded during the study (with an absolute increase of sum at least 5 mm), or the appearance of ≥ 1 new lesions), or death due to any cause According to PCWG3, progression is defined as: two or more new lesions detected on the first post-baseline scan with at least 2 additional lesions on a subsequent scan; two or more new lesions detected on a subsequent scan (if one or no new lesions were seen at the first post-baseline scan) and confirmed by a follow-up scan	Up to day 337 (visit 16)
Prostate-specific antigen (PSA) response rate (%) in RS-113 treatment arms	Prostate-specific antigen (PSA) response rate (%) in RS-113 treatment arms	at Week 9, 21, 33, 45, 57, 69, 81, 93, 101 and FU visit
Number (%) of patients achieved ≥50% prostate-specific antigen (PSA) decline in RS-113 treatment arms	Number (%) of patients achieved ≥50% PSA decline at 6, 12, 18 and 24 months in RS-113 treatment arms Defined as a ≥50% reduction in PSA level from baseline at any time post-baseline. The response must be confirmed by the next PSA assessment performed at least 2 weeks later	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Number (%) of patients achieved ≥90% prostate-specific antigen (PSA) decline in RS-113 treatment arm	Number (%) of patients achieved ≥90% PSA decline at 6, 12, 18 and 24 months in RS-113 treatment arm Defined as a ≥90% reduction in PSA level from baseline at any time post-baseline. The response must be confirmed by the next PSA assessment performed at least 2 weeks later	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Objective response rate (ORR)(%) at 1 year in RS-113 treatment arms	The objective response rate (ORR)(%) is defined as the percentage of patients in RS-113 treatment arms who achieve a complete or partial response per RECIST 1.1: Complete response (CR): disappearance of all target lesions confirmed by CT for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be < 10 mm; Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions sustained for at least 4 weeks taking as reference the baseline sum at screening	once at screening, on days 57 (visit 5), 113 (visit 8), 169 (visit 10), 253 (visit 13), 337 (visit 16) and FU visit
Disease control rate (DCR)(%) at 1 year in RS-113 treatment arms	The disease control rate is defined as the percentage of patients in RS-113 treatment arms who achieve a complete response, partial response, or stable disease during treatment per RECIST 1.1: Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be <10 mm; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks taking as reference the baseline (screening) measurements; Stable Disease (SD) - neither sufficient shrinkage in the sum of diameters to qualify as partial response nor sufficient increase to qualify as progressive disease taking as reference the smallest sum recorded during the study	once at screening, on days 57 (visit 5), 113 (visit 8), 169 (visit 10), 253 (visit 13), 337 (visit 16) and FU visit
Time to Tumor Response (TTR) at 1 year in RS-113 treatment arms	Time to Tumor Response (TTR) at 1 year in RS-113 treatment arms	once at screening, on days 57 (visit 5), 113 (visit 8), 169 (visit 10), 253 (visit 13), 337 (visit 16) and FU visit
Duration of Response (DOR) at 1 year in RS-113 treatment arms	Duration of Response (DOR) at 1 year in RS-113 treatment arms	once at screening, on days 57 (visit 5), 113 (visit 8), 169 (visit 10), 253 (visit 13), 337 (visit 16) and FU visit
Time to prostate-specific antigen (PSA) progression in RS-113 treatment arms	Time to PSA progression is the time from randomization to the earliest date of confirmed PSA progression (per PCWG3 criteria). The date of PSA progression is defined as the date of a documented ≥25% increase in PSA and an absolute increase of ≥2 ng/mL above the nadir (or above baseline for patients with no PSA decline by Week 12), confirmed by two consecutive values obtained at least 3 weeks apart	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Radiographic Progression-Free Survival (rPFS) at 1 year in RS-113 treatment arms	Radiographic Progression-Free Survival (rPFS) in RS-113 treatment arms, expressed as median rPFS for a period of up to 1 year of treatment inclusive (defined as the time from randomization to the first objective evidence of radiographic disease progression per RECIST 1.1 criteria or death due to any cause)	Up to day 337 (visit 16)
Overall survival (OS) rate (%) at 1 year in RS-113 treatment arms	Overall survival (OS) expressed as the rate (%) at 1 year OS in RS-113 treatment arms	Up to day 337 (visit 16)
Number of patients (%) with adverse drug reactions (ADRs) of any severity	Number of patients (%) with adverse drug reactions (ADRs) of any severity	Up to day 701 (visit 29)
Number of patients (%) with adverse events (AEs) of any severity	Number of patients (%) with adverse events (AEs) of any severity	Up to day 701 (visit 29)
Number of patients (%) with AEs grade ≥ 3 per CTCAE v. 5.0	Number of patients (%) with AEs grade ≥ 3 per CTCAE v. 5.0	Up to day 701 (visit 29)
Number of patients (%) with ADRs grade ≥ 3 per CTCAE v. 5.0	Number of patients (%) with ADRs grade ≥ 3 per CTCAE v. 5.0	Up to day 701 (visit 29)
Number of patients (%) with serious adverse events (SAEs)	Number of patients (%) with serious adverse events (SAEs) SAEs will be graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0	Up to day 701 (visit 29)
Number of patients (%) with serious adverse drug reactions (SADRs)	Number of patients (%) with serious adverse drug reactions (SADRs) SADRs will be graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0	Up to day 701 (visit 29)
Number of patients (%) who required discontinuation of treatment due to development of ADRs	Number of patients (%) who required discontinuation of treatment due to development of ADRs ADRs will be graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0	Up to day 701 (visit 29)
Number of patients (%) who required discontinuation of treatment due to development of SADRs	Number of patients (%) who required discontinuation of treatment due to development of SADRs SADRs will be graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0	Up to day 701 (visit 29)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median progression-free survival (PFS) at 1 year (comparative assesment)	Progression-free survival (PFS) expressed as the median PFS for a period of up to 1 year of treatment inclusive (per RECIST 1.1 and PCWG3 criteria) (comparative assessment of median PFS at 1 year in each RS-113 treatment arm versus abiraterone plus prednisolone) PFS is defined as the time from randomization to disease progression per RECIST 1.1 (an ≥ 20% increase in the sum of diameters of target lesions taking as reference the smallest sum recorded during the study (with an absolute increase of sum at least 5 mm), or the appearance of ≥ 1 new lesions), or death due to any cause According to PCWG3, progression is defined as: two or more new lesions detected on the first post-baseline scan with at least 2 additional lesions on a subsequent scan; two or more new lesions detected on a subsequent scan (if one or no new lesions were seen at the first post-baseline scan) and confirmed by a follow-up scan	Up to day 337 (visit 16)
Progression-free survival (PFS) rate (%) at 1 year (comparative assessment)	Progression-free survival (PFS) expressed as the rate (%) at 1 year PFS (per RECIST 1.1 and PCWG3 criteria) (comparative assessment of PFS rate (%) at 1 year in each RS-113 treatment arm versus abiraterone plus prednisolone) PFS is defined as the time from randomization to disease progression per RECIST 1.1 (an ≥ 20% increase in the sum of diameters of target lesions taking as reference the smallest sum recorded during the study (with an absolute increase of sum at least 5 mm), or the appearance of ≥ 1 new lesions), or death due to any cause According to PCWG3, progression is defined as: two or more new lesions detected on the first post-baseline scan with at least 2 additional lesions on a subsequent scan; two or more new lesions detected on a subsequent scan (if one or no new lesions were seen at the first post-baseline scan) and confirmed by a follow-up scan	Up to day 337 (visit 16)
Median progression-free survival (PFS) at 2 years (comparative assesment)	Progression-free survival (PFS) expressed as the median PFS for a period of up to 2 years of treatment inclusive (per RECIST 1.1 and PCWG3 criteria) (comparative assessment of median PFS at 2 years in each RS-113 treatment arm versus abiraterone plus prednisolone) PFS is defined as the time from randomization to disease progression per RECIST 1.1 (an ≥ 20% increase in the sum of diameters of target lesions taking as reference the smallest sum recorded during the study (with an absolute increase of sum at least 5 mm), or the appearance of ≥ 1 new lesions), or death due to any cause According to PCWG3, progression is defined as: two or more new lesions detected on the first post-baseline scan with at least 2 additional lesions on a subsequent scan; two or more new lesions detected on a subsequent scan (if one or no new lesions were seen at the first post-baseline scan) and confirmed by a follow-up scan	Up to day 701 (visit 29)
Progression-free survival (PFS) rate (%) at 2 years (comparative assessment)	Progression-free survival (PFS) expressed as the rate (%) of 2-years PFS (per RECIST 1.1 and PCWG3 criteria) (comparative assessment of PFS rate (%) at 2 years in each RS-113 treatment arm versus abiraterone plus prednisolone) PFS is defined as the time from randomization to disease progression per RECIST 1.1 (an ≥ 20% increase in the sum of diameters of target lesions taking as reference the smallest sum recorded during the study (with an absolute increase of sum at least 5 mm), or the appearance of ≥ 1 new lesions), or death due to any cause According to PCWG3, progression is defined as: two or more new lesions detected on the first post-baseline scan with at least 2 additional lesions on a subsequent scan; two or more new lesions detected on a subsequent scan (if one or no new lesions were seen at the first post-baseline scan) and confirmed by a follow-up scan	Up to day 701 (visit 29)
Prostate-specific antigen (PSA) response rate (%) (comparative assessment)	Prostate-specific antigen (PSA) response rate (%) (comparative assessment of PSA response rate (%) in each RS-113 treatment arm versus abiraterone plus prednisolone)	once at screening, on days 57 (week 9), 141 (week 21), 225 (week 33), 309 (week 45), 393 (week 57), 477 (week 69), 561 (week 81), 645 (week 93), 701 (week 101) and FU visit
Number (%) of patients achieved ≥50% prostate-specific antigen (PSA) decline (comparative assessment)	Number (%) of patients achieved ≥50% PSA decline at 6, 12, 18 and 24 months (comparative assessment of PSA response rate (%) in each RS-113 treatment arm versus abiraterone plus prednisolone) Defined as a ≥50% reduction in PSA level from baseline at any time post-baseline. The response must be confirmed by the next PSA assessment performed at least 2 weeks later	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Number (%) of patients achieved ≥90% prostate-specific antigen (PSA) decline (comparative assessment)	Number (%) of patients achieved ≥90% PSA decline at 6, 12, 18 and 24 months (comparative assessment of PSA response rate (%) in each RS-113 treatment arm versus abiraterone plus prednisolone) Defined as a ≥90% reduction in PSA level from baseline at any time post-baseline. The response must be confirmed by the next PSA assessment performed at least 2 weeks later	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Objective response rate (ORR)(%) at 1 year (comparative assessment)	Objective response rate (ORR)(%) at 1 year (comparative assessment of ORR in each RS-113 treatment arm versus abiraterone plus prednisolone) The ORR is defined as the percentage of patients in each RS-113 treatment arm versus abiraterone plus prednisolone who achieve a complete or partial response per RECIST 1.1: Complete response (CR): disappearance of all target lesions confirmed by CT for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be < 10 mm; Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions sustained for at least 4 weeks taking as reference the baseline sum at screening	once at screening, on days 57 (visit 5), (visit 8), 113 (visit 10), 253 (visit 13), 337 (visit 16) and FU visit
Objective response rate (ORR)(%) at 2 years (comparative assessment)	Objective response rate (ORR)(%) at 2 years (comparative assessment of ORR in each RS-113 treatment arm versus abiraterone plus prednisolone) The ORR is defined as the percentage of patients in each RS-113 treatment arm versus abiraterone plus prednisolone who achieve a complete or partial response per RECIST 1.1: Complete response (CR): disappearance of all target lesions confirmed by CT for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be < 10 mm; Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions sustained for at least 4 weeks taking as reference the baseline sum at screening	once at screening, on days 57 (visit 5), (visit 8), 113 (visit 10), 253 (visit 13), 337 (visit 16), 421 (visit 19), 505 (visit 22), 589 (visit 25), 673 (visit 28) and FU visit
Disease control rate (DCR)(%) at 1 year (comparative assessment)	Disease control rate (DCR)(%) at 1 year (comparative assessment of DCR in each RS-113 treatment arm versus abiraterone plus prednisolone) The DCR is defined as the percentage of patients in each RS-113 treatment arm versus abiraterone plus prednisolone who achieve a complete response, partial response, or stable disease during treatment per RECIST 1.1: Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be <10 mm; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks taking as reference baseline (screening) measurements; Stable Disease (SD) - neither sufficient shrinkage in the sum of diameters to qualify as partial response nor sufficient increase to qualify as progressive disease taking as reference the smallest sum recorded during the study	once at screening, on days 57 (visit 5), (visit 8), 113 (visit 10), 253 (visit 13), 337 (visit 16) and FU visit
Disease control rate (DCR)(%) at 2 years (comparative assessment)	Disease control rate (DCR)(%) at 2 years (comparative assessment of DCR in each RS-113 treatment arm versus abiraterone plus prednisolone) The DCR is defined as the percentage of patients in each RS-113 treatment arm versus abiraterone plus prednisolone who achieve a complete response, partial response, or stable disease during treatment per RECIST 1.1: Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be <10 mm; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks taking as reference baseline (screening) measurements; Stable Disease (SD) - neither sufficient shrinkage in the sum of diameters to qualify as partial response nor sufficient increase to qualify as progressive disease taking as reference the smallest sum recorded during the study	once at screening, on days 57 (visit 5), (visit 8), 113 (visit 10), 253 (visit 13), 337 (visit 16), 421 (visit 19), 505 (visit 22), 589 (visit 25), 673 (visit 28) and FU visit
Time to Tumor Response (TTR) at 1 year (comparative assessment)	Time to Tumor Response (TTR) at 1 year (comparative assessment of TTR in each RS-113 treatment arm versus abiraterone plus prednisolone)	once at screening, on days 57 (visit 5), (visit 8), 113 (visit 10), 253 (visit 13), 337 (visit 16) and FU visit
Time to Tumor Response (TTR) at 2 years (comparative assessment)	Time to Tumor Response (TTR) at 2 years (comparative assessment of TTR in each RS-113 treatment arm versus abiraterone plus prednisolone)	once at screening, on days 57 (visit 5), (visit 8), 113 (visit 10), 253 (visit 13), 337 (visit 16), 421 (visit 19), 505 (visit 22), 589 (visit 25), 673 (visit 28) and FU visit
Duration of Response (DOR) at 1 year (comparative assessment)	Duration of Response (DOR) at 1 year (comparative assessment of DOR in each RS-113 treatment arm versus abiraterone plus prednisolone)	once at screening, on days 57 (visit 5), (visit 8), 113 (visit 10), 253 (visit 13), 337 (visit 16) and FU visit
Duration of Response (DOR) at 2 years (comparative assessment)	Duration of Response (DOR) at 2 years (comparative assessment of DOR in each RS-113 treatment arm versus abiraterone plus prednisolone)	once at screening, on days 57 (visit 5), (visit 8), 113 (visit 10), 253 (visit 13), 337 (visit 16), 421 (visit 19), 505 (visit 22), 589 (visit 25), 673 (visit 28) and FU visit
Time to prostate-specific antigen (PSA) progression (comparative assessment)	Time to prostate-specific antigen (PSA) progression (comparative assessment of time to PSA progression in each RS-113 treatment arm versus abiraterone plus prednisolone) Time to PSA progression is the time from randomization to the earliest date of confirmed PSA progression (per PCWG3 criteria). The date of PSA progression is defined as the date of a documented ≥25% increase in PSA and an absolute increase of ≥2 ng/mL above the nadir (or above baseline for patients with no PSA decline by Week 12), confirmed by two consecutive values obtained at least 3 weeks apart	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Radiographic Progression-Free Survival (rPFS) at 1 year in each RS-113 treatment arm versus abiraterone plus prednisolone (comparative assessment)	Radiographic Progression-Free Survival (rPFS) in each RS-113 treatment arm versus abiraterone plus prednisolone, expressed as median rPFS for a period of up to 1 year of treatment inclusive (defined as the time from randomization to the first objective evidence of radiographic disease progression per RECIST 1.1 criteria or death due to any cause)(comparative assessment of rPFS in each RS-113 treatment arm versus abiraterone plus prednisolone)	Up to day 337 (visit 16)
Radiographic Progression-Free Survival (rPFS) at 2 years in each RS-113 treatment arm versus abiraterone plus prednisolone (comparative assessment)	Radiographic Progression-Free Survival (rPFS) in each RS-113 treatment arm versus abiraterone plus prednisolone, expressed as median rPFS for a period of up to 2 years of treatment inclusive (defined as the time from randomization to the first objective evidence of radiographic disease progression per RECIST 1.1 criteria or death due to any cause)(comparative assessment of rPFS in each RS-113 treatment arm versus abiraterone plus prednisolone)	Up to day 701 (visit 29)
Change in pain intensity from baseline per the BPI-SF questionnaire (comparative assessment)	Change in pain intensity from baseline per the BPI-SF questionnaire at 6, 12, 18, and 24 months of treatment, and at the first follow-up visit (comparative assessment in each RS-113 treatment arm versus abiraterone plus prednisolone) When completing the BPI-SF (Brief Pain Inventory-Short Form), patients identify pain locations (graphically on a body diagram), rate pain intensity (from 0 [no pain] to 10 [pain as bad as you can imagine]), and assess the degree of pain interference with quality of life (from 0 [does not interfere] to 10 [completely interferes])	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Time to pain progression per the BPI-SF questionnaire (comparative assessment)	Time to pain progression per the BPI-SF questionnaire (comparative assessment in each RS-113 treatment arm versus abiraterone plus prednisolone) Time to pain progression is the interval from baseline to the date when the participant, according to Item 3 of the Brief Pain Inventory-Short Form (BPI-SF), demonstrates a ≥2-point increase in pain intensity from baseline, observed at two consecutive assessments ≥4 weeks apart, or the initiation of regular opioid use, whichever occurs first	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Change in quality of life from baseline per the FACT-P (version 4) questionnaire (comparative assessment)	Change in quality of life from baseline per the FACT-P (version 4) questionnaire at 6, 12, 18, and 24 months of treatment, and at the first follow-up visit (comparative assessment in each RS-113 treatment arm versus abiraterone plus prednisolone)	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Change in quality of life from baseline per the EQ-5D-5L questionnaire (comparative assessment)	Change in quality of life from baseline per the EQ-5D-5L) questionnaire at 6, 12, 18, and 24 months of treatment, and at the first follow-up visit (comparative assessment in each RS-113 treatment arm versus abiraterone plus prednisolone)	once at screening, on days 29 (visit 3), 57 (visit 5), 85-701 (visits 7-29) and FU visit
Overall survival (OS) rate (%) at 1 year (comparative assessment)	Overall survival (OS) expressed as the rate (%) at 1 year OS (comparative assessment in each RS-113 treatment arm versus abiraterone plus prednisolone)	Up to day 337 (visit 16)
Overall survival (OS) rate (%) at 2 years (comparative assessment)	Overall survival (OS) expressed as the rate (%) of 2-years OS (comparative assessment in each RS-113 treatment arm versus abiraterone plus prednisolone)	Up to day 701 (visit 29)
Area under the plasma drug concentration-time curve (AUC) of RS-113 from time 0 to 24 hours (AUC(0-24))	Area under the plasma drug concentration-time curve (AUC) of RS-113 from time 0 to 24 hours after the first (single dose) dose, truncated at the point before the second dose, i.e. up to 24 hours (AUC(0-24))	Pre-dose on Day 1 (<30 min before the first dose) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose
Maximum plasma concentration of RS-113 after the first dose (Cmax)	Maximum plasma concentration of RS-113 after the first dose (Cmax)	Pre-dose on Day 1 (<30 min before the first dose) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose
Time to reach maximum (peak) plasma concentration of RS-113 following the first dose (Tmax)	Time to reach maximum (peak) plasma concentration of RS-113 following the first dose (Tmax)	Pre-dose on Day 1 (<30 min before the first dose) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose
Volume of distribution of RS-113 after the first dose (Vd)	Volume of distribution of RS-113 after the first dose (Vd)	Pre-dose on Day 1 (<30 min before the first dose) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose
Maximum plasma concentration of RS-113 at steady state (Cmax ss)	Maximum plasma concentration of RS-113 at steady state (Cmax ss)	Pre-dose on Day 15 (<30 min before the 15th administration) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose
Minimum plasma concentration of RS-113 at steady state (Cmin ss)	Minimum plasma concentration of RS-113 at steady state (Cmin ss)	Pre-dose on Day 15 (<30 min before the 15th dose) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose
Area under the plasma drug concentration-time curve (AUC) of RS-113 at steady state (AUCtau ss)	Area under the plasma drug concentration-time curve (AUC) of RS-113 at steady state (AUCtau ss)	Pre-dose on Day 15 (<30 min before the 15th dose) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose
Time to reach maximum (peak) plasma concentration of RS-113 at steady state (Tmax ss)	Time to reach maximum (peak) plasma concentration of RS-113 at steady state (Tmax ss)	Pre-dose on Day 15 (<30 min before the 15th dose) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose
Volume of distribution of RS-113 at steady state (Vd ss)	Volume of distribution of RS-113 at steady state (Vd ss)	Pre-dose on Day 15 (<30 min before the 15th dose) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose
Residual concentration of RS-113 at steady state (Cthrough)	Residual concentration of RS-113 at steady state (Cthrough)	Pre-dose on Day 15 (<30 min before the 15th dose) and 3 h ± 15 min, 6 h ± 30 min, 10 h ± 30 min, 14 h ± 30 min, 17 h ± 30 min, 22 h ± 30 min, 23 h 55 min ± 30 min post-dose

Collaborators and Investigators

• Sponsor: R-Pharm International, LLC
• Investigators: Study Director: Mikhail Samsonov, R-Pharm

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2024
• Primary Completion (Estimated): May 14, 2026
• Study Completion (Estimated): May 9, 2027

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Metastatic Castration-resistant Prostate Cancer; RS-113
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Pharmacologic Actions; Chemical Actions and Uses; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Prednisolone; Androgen Antagonists; abiraterone
• Other Study ID Numbers: CL01069052

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No