A Phase 3 Study of [177Lu]Ludotadipep for Metastatic Castration-Resistant Prostate Cancer

A Multi-center, Open-label, Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of [177Lu]Ludotadipep Treatment for Metastatic Castration-resistant Prostate Cancer

Primary Efficacy Endpoint

- Radiographic Progression-Free Survival (rPFS): rPFS is defined as the time from randomization to radiographic disease progression (PD), as assessed by Blinded Independent Central Review (BICR) according to PCWG3-modified RECIST version 1.1, or death from any cause, whichever occurs first.

rPFS will be analyzed using the Kaplan-Meier method. The median survival time and corresponding two-sided 95% confidence intervals (CIs) will be estimated for both the investigational and control arms, and Kaplan-Meier curves will be presented.

A comparison between the investigational and control arms will be performed using a stratified Cox proportional hazards regression model. The model will be adjusted for the following stratification factors: nomogram score (≥178 vs <178), ECOG Performance Status (0 or 1 vs 2), prior use of cabazitaxel before randomization (yes vs no), and receipt of best supportive care alone (yes vs no). The p-value will be reported.

Ties in event times will be handled using the Efron method. The hazard ratio (HR) of the investigational arm relative to the control arm and its corresponding two-sided 95% confidence interval will be provided.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; mCRPC
• Intervention / Treatment: Drug: [177-Lu]Ludotadipep; Other: Best supportive care/standard of care (BSC/SOC) alone

Detailed Description

Study Procedures:

• Before randomization, investigators determine the most appropriate BSC/SoC for each participant.
• Participants start BSC/SoC from Cycle 1 Day 1 (C1D1). [177-Lu]Ludotadipep is administered every 8 weeks for up to 4 cycles; investigators may allow up to 6 cycles based on clinical judgment. (Participants who do not meet criteria or decline additional [177-Lu]Ludotadipep after 4 cycles will continue BSC/SoC alone.)
• Control arm participants who experience radiographic disease progression may cross over to receive [177-Lu]Ludotadipep in combination with BSC/SoC after obtaining separate consent and confirming eligibility.
• "Cross-over" is defined as [177-Lu]Ludotadipep treatment in the control arm after progression. "Cross-over screening" refers to the eligibility confirmation process for cross-over.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chan Soo Park; Phone Number: +82 70 5066 2479; Email: chansoo.park@futurechem.co.kr

Study Locations

• South Korea
  • Gyeonggi-do, South Korea
    • Recruiting
    • National Cancer Center
    • Contact: Jae Young Joung; Phone Number: 82 1588 8110; Email: urojy@ncc.re.kr
  • Seoul, South Korea
    • Recruiting
    • Samsung Medical Center
    • Contact: Seong Soo Jeon; Phone Number: +82 2 3410 0200; Email: seongsoo.jeon@samsung.com
  • Seoul, South Korea
    • Recruiting
    • Seoul National University Hospital
    • Contact: Cheol Kwak; Phone Number: +82 2 1588 5700; Email: mdrafael@snu.ac.kr
  • Seoul, South Korea
    • Recruiting
    • Severance Hospital
    • Contact: Seung Hwan Lee; Phone Number: 82 2 1599 1004; Email: LEESEH@yuhs.ac
  • Seoul, South Korea
    • Recruiting
    • Seoul St. Mary's Hospital
    • Contact: Ji Youl Lee; Phone Number: +82 2 1588-1511; Email: uroljy@catholic.ac.kr
  • Seoul, South Korea
    • Recruiting
    • Ewha Woman University Medical Center
    • Contact: Cheong Soo Kim; Phone Number: 82 2 8650 5114; Email: cskim37345806@gmail.com
  • Seoul, South Korea
    • Not yet recruiting
    • Korea University ANAM Hospital
    • Contact: Seok Ho Kang; Phone Number: 82 2 1577 0083; Email: mdksh@korea.ac.kr
  • Suwon, South Korea
    • Recruiting
    • St. Vincent's Hospital
    • Contact: Seung Ju Lee; Phone Number: 82 1577 8588; Email: lee.seungju@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Adult male aged ≥19 years at the time of written informed consent.

2. Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma without small cell features.

3. Patients with progressive metastatic castration-resistant prostate cancer (mCRPC) meeting at least one of the following criteria:

   1. PSA progression: Minimum PSA level of ≥2.0 ng/mL with at least two consecutive increases at intervals of ≥1 week.
   2. Soft tissue progression:

   i. ≥20% increase in the sum of diameters (SOD)* of target lesions compared to the smallest SOD since treatment initiation, or ii. Appearance of one or more new lesions.

   *Short axis for lymph nodes and long axis for non-nodal lesions. (c) Bone progression: Appearance of ≥2 new lesions on bone scan.

4. At least one metastatic lesion documented by CT, MRI, or bone scan within 4 weeks prior to baseline.

5. Castration-resistant status with serum testosterone ≤50 ng/dL (≤1.7 nmol/L), achieved by surgical or medical castration.

   Patients without bilateral orchiectomy receiving LHRH analogs must continue such therapy throughout the study.

6. Prior therapy meeting all of the following:

   1. At least one novel anti-androgen drug (NAAD) (e.g., enzalutamide and/or abiraterone).

      (First-generation anti-androgens such as bicalutamide, flutamide, and nilutamide are not counted.)

   2. At least one, but no more than two, prior taxane regimens. Patients who have not received docetaxel may be enrolled if deemed unsuitable, refused treatment, or lack access.

7. COG performance status ≤2.

8. Life expectancy of at least 24 weeks.

9. PSMA-positive mCRPC confirmed by [18F]PSMA PET/CT at screening by independent central review, meeting all of the following:

   1. At least one PSMA-positive metastatic lesion§.

      §Defined as uptake greater than liver background, regardless of organ system or lesion size.

   2. No PSMA-negative lesions∥. ∥Defined as metastatic lesions with uptake equal to or lower than liver background and measurable on CT¶.

      • i. Bone lesions with soft tissue component ≥1 cm (short axis) ii. Solid organ metastases ≥1 cm (short axis) iii. Lymph nodes ≥2.5 cm (short axis)

10. Adequate bone marrow, hepatic, and renal function at screening (one repeat test allowed during screening).

11. Agreement to avoid fathering a child and to use effective contraception from screening until 24 weeks after the last dose of study drug, and to refrain from sperm donation.

    Acceptable contraception methods include hormonal contraception, intrauterine device/system, surgical sterilization, double-barrier methods, or complete abstinence.

12. Planned best supportive care/standard of care (BSC/SoC) must be permitted in this study, and both investigator and patient agree that disease management with BSC/SoC alone is appropriate.

13. Ability to understand the study and provision of written informed consent prior to any study-specific procedures.

Exclusion Criteria:

1. Prior treatment with any of the following therapies:

   1. PSMA-targeted radioligand therapy
   2. Systemic radionuclide therapy within 24 weeks prior to the first dose of study intervention (e.g., strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, or hemi-body irradiation)
   3. Any other anticancer therapy (including cytotoxic chemotherapy, immunotherapy, biologic therapy, or targeted therapy) within 4 weeks prior to randomization

2. History of any of the following:

   1. Hypersensitivity to the active substance or any component of the investigation
   2. History of another primary malignancy within 3 years prior to screening, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, papillary thyroid cancer, or carcinoma in situ with no recurrence for at least 2 years, as judged by the investigator
   3. Clinically significant cardiovascular disease within 24 weeks prior to screening, including but not limited to:

   i. Myocardial infarction or severe/unstable angina ii. Congestive heart failure (NYHA Class III or IV) iii. QTcF >480 msec on ECG iv. Clinically significant seizures or conditions predisposing to seizures v. Symptomatic or impending spinal cord compression (d) Known human immunodeficiency virus (HIV) infection

3. Presence of any of the following comorbidities:

   1. Uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥90 mmHg)
   2. Symptomatic or uncontrolled central nervous system metastases (Patients may be eligible if clinically and radiologically stable for ≥4 weeks and off anticonvulsants and corticosteroids for ≥2 weeks prior to study treatment)
   3. Immunocompromised status (including splenectomy or hematopoietic stem cell transplantation) or active autoimmune disease (e.g., myasthenia gravis, Hashimoto's thyroiditis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, scleroderma)
   4. Severe infection or other uncontrolled active infection that may interfere with study assessments, as judged by the investigator
   5. Active hepatitis B or C infection:

   Hepatitis B: Defined as HBsAg positive at screening; however, patients may be eligible if HBV DNA <500 IU/mL and on stable antiviral therapy for ≥2 weeks prior to first dose, with intent to continue during the study and for ≥24 weeks after the last dose Hepatitis C: Defined as HCV antibody positive; patients are eligible if HCV RNA is negative

4. Presence of a superscan on bone scan at baseline.

5. Failure to recover to baseline or ≤ Grade 1 from prior anticancer therapy-related toxicities (except for alopecia of any grade or other conditions deemed acceptable per eligibility criteria).

6. Participation in another clinical study with administration of an investigational product or device within 4 weeks prior to the first dose of study intervention.

7. Any other condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [177-Lu]Ludotadipep plus best supportive care/standard of care (BSC/SOC); Each participant will receive 3.7 GBq (+/- 10%) [177-Lu]Ludotadipep every 8 weeks for a total of 4 cycles, with the possibility of up to 6 cycles based on clinical judgment. Best supportive care/standard of care (BSC/BSOC) might be used.	Drug: [177-Lu]Ludotadipep; [177-Lu]Ludotadipep 3.7 GBq (+/- 10%) intravenously every 8 weeks for a maximum of 6 cycles.; Other: Best supportive care/standard of care (BSC/SOC) alone; Best supportive care/standard of care as defined by the investigator.
Active Comparator: BSC/SoC; Control arms will receive best supportive care/standard of care (BSC/SoC) permitted in the trial, according to the investigator's discretion and the standard practices of the study site.	Other: Best supportive care/standard of care (BSC/SOC) alone; Best supportive care/standard of care as defined by the investigator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Progression-Free Survival (rPFS)	Radiographic progression-free survival (rPFS) is defined as the time from the date of randomization to the date of first documented radiographic disease progression or death from any cause, whichever occurs first, as assessed by blinded independent central review (BICR) according to PCWG3-modified RECIST version 1.1. Median rPFS and two-sided 95% confidence intervals (CIs) for each treatment group will be estimated using the Kaplan-Meier method, and Kaplan-Meier curves will be presented. Treatment groups will be compared using a stratified Cox proportional hazards regression analysis, adjusting for stratification factors (nomogram score [>178 vs. ≤178], ECOG performance status [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone). Ties will be handled using the Efron method. The hazard ratio (HR) for the treatment group relative to the control group, along with its two-sided 95% CI and corresponding p-value, will be reported.	up to 36 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Progression-Free Survival (rPFS)	Radiographic progression-free survival (rPFS) is defined as the Time from the date of randomization to the date of first documented radiographic disease progression or death from any cause, whichever occurs first, as assessed by blinded independent central review (BICR) and investigator according to RECIST version 1.1 and RECIP 1.0(RECIP BICR Only). Median rPFS and two-sided 95% confidence intervals (CIs) for each treatment group will be estimated using the Kaplan-Meier method, and Kaplan-Meier curves will be presented. Treatment groups will be compared using a stratified Cox proportional hazards regression analysis, adjusting for stratification factors (nomogram score [>178 vs. ≤178], ECOG performance status [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone). Ties will be handled using the Efron method. The hazard ratio (HR) for the treatment group relative to the control group, along with its two-sided 95% CI and corresponding p-value, will be reported.	up to 36 months.
Overall Survival (OS)	Overall survival (OS) is defined as the time from the date of randomization to the date of death from any cause. Median OS and two-sided 95% confidence intervals (CIs) for each treatment group will be estimated using the Kaplan-Meier method, and Kaplan-Meier curves will be presented. Treatment groups will be compared using a stratified Cox proportional hazards regression analysis, adjusting for stratification factors (nomogram score [>178 vs. ≤178], ECOG performance status [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone). Ties will be handled using the Efron method. The hazard ratio (HR) for the treatment group relative to the control group, along with its two-sided 95% CI and corresponding p-value, will be reported.	up to 36 months.
Duration of Response (DOR)	Duration of response (DOR) is defined as the time from the date of first documented partial response (PR) or complete response (CR) to the date of first documented radiographic disease progression (PD), as assessed by blinded independent central review (BICR) and investigator according to RECIST v1.1, PCWG3-modified RECIST v1.1, and RECIP 1.0 (RECIP BICR only). Median DOR and two-sided 95% confidence intervals (CIs) for each treatment group will be estimated using the Kaplan-Meier method, and Kaplan-Meier curves will be presented. Treatment groups will be compared using a stratified Cox proportional hazards regression analysis, adjusting for stratification factors (nomogram score [>178 vs. ≤178], ECOG performance status [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone). Ties will be handled using the Efron method. The hazard ratio (HR) for the treatment group relative to the control group, along with its two-sided 95% CI and corresponding p-value, will be reported.	up to 36 months.
Progression-Free Survival (PFS)	Progression-free survival (PFS) is defined as the time from the date of randomization to the date of first documented radiographic progression, PSA progression, clinical progression, or death from any cause, whichever occurs first, as assessed by investigator according to RECIST v1.1 and PCWG3-modified RECIST v1.1. Median PFS and two-sided 95% confidence intervals (CIs) for each treatment group will be estimated using the Kaplan-Meier method, and Kaplan-Meier curves will be presented. Treatment groups will be compared using a stratified Cox proportional hazards regression analysis, adjusting for stratification factors (nomogram score [>178 vs. ≤178], ECOG performance status [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone). Ties will be handled using the Efron method. The hazard ratio (HR) for the treatment group relative to the control group, along with its two-sided 95% CI and corresponding p-value, will be reported.	up to 36 months.
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the proportion (%) of participants who achieve a best overall response of complete response (CR) or partial response (PR), as assessed by BICR and investigator according to RECIST v1.1, PCWG3-modified RECIST v1.1, and RECIP 1.0 (RECIP 1.0 assessed by BICR only). Frequencies, percentages, and two-sided 95% CIs will be presented for each treatment group. Between-group comparisons will be performed using a stratified logistic regression model, adjusting for stratification factors (nomogram score [>178 vs. ≤178], ECOG performance status [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone). The odds ratio (OR) for the treatment group relative to the control group, along with its two-sided 95% CI and corresponding p-value, will be reported.	up to 36 months.
Health-Related Quality of Life (HRQoL) - BPI-SF (Brief Pain Inventory - Short Form)	Evaluated using Brief Pain Inventory - Short Form (BPI-SF). Pain severity items range from 0 (no pain) to 10 (pain as bad as you can imagine), calculated as the mean of 4 items. Pain interference items range from 0 (does not interfere) to 10 (completely interferes), calculated as the mean of 7 items. Lower scores represent less pain and interference (better outcome); higher scores represent greater pain and interference (worse outcome). Summary statistics (N, mean, SD, median, min, max) for baseline and post-baseline will be reported. Between-group comparisons will be analyzed using Analysis of Covariance (ANCOVA) on change from baseline, with treatment group as a fixed effect, and baseline score and stratification factors (nomogram score, ECOG PS, prior cabazitaxel use, BSC alone) as covariates. LSM, SE, LSM differences with 95% CIs, and p-values will be reported.	Baseline and Day 1 of each cycle during treatment
Biochemical Response - Best PSA Response Rate (best PSA-RR)	Best prostate-specific antigen response rate (best PSA-RR) is defined as the proportion (%) of subjects with a ≥50% reduction in Prostate-Specific Antigen (PSA) levels from baseline. Frequencies and percentages for each treatment group will be presented. Between-group comparisons will be performed using a stratified logistic regression model, adjusting for stratification factors (nomogram score [>178 vs. ≤178], ECOG performance status [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone). The odds ratio (OR) for the treatment group relative to the control group, along with its two-sided 95% confidence interval (CI) and corresponding p-value, will be reported.	Up to 36 months
Health-Related Quality of Life (HRQoL) - FACT-P (Functional Assessment of Cancer Therapy - Prostate)	Evaluated using Functional Assessment of Cancer Therapy - Prostate (FACT-P) total score (27-item FACT-General plus 12-item Prostate Cancer Subscale). Total scores range from 0 to 156, with higher scores indicating better quality of life. Questionnaire is completed prior to IP administration on Day 1 of each cycle. Summary statistics (N, mean, SD, median, min, max) for baseline and post-baseline will be reported. Between-group comparisons will be analyzed using ANCOVA on change from baseline, with treatment group as a fixed effect, and baseline score and stratification factors (nomogram score [>178 vs. ≤178], ECOG PS [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone) as covariates. LSM, SE, LSM differences with 95% CIs, and p-values will be reported.	Baseline and Day 1 of each cycle during treatment
Biochemical Response - Changes in LDH (Lactate Dehydrogenase)	Evaluated by the change from baseline in serum lactate dehydrogenase (LDH) level at specified time points. Summary statistics (N, mean, SD, median, min, max) for baseline and post-baseline will be reported. Between-group comparisons will be analyzed using ANCOVA on change from baseline, with treatment group as a fixed effect, and baseline LDH level and stratification factors (nomogram score [>178 vs. ≤178], ECOG PS [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone) as covariates. LSM, SE, LSM differences with 95% CIs, and p-values will be reported.	Baseline and scheduled study visits up to 36 months
Biochemical Response - Changes in ALP (Alkaline Phosphatase)	Evaluated by the change from baseline in serum alkaline phosphatase (ALP) level at specified time points. Summary statistics (N, mean, SD, median, min, max) for baseline and post-baseline will be reported. Between-group comparisons will be analyzed using ANCOVA on change from baseline, with treatment group as a fixed effect, and baseline ALP level and stratification factors (nomogram score [>178 vs. ≤178], ECOG PS [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone) as covariates. LSM, SE, LSM differences with 95% CIs, and p-values will be reported.	Baseline and scheduled study visits up to 36 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) is defined as the proportion (%) of subjects who achieved Complete Response (CR), Partial Response (PR), or Stable Disease (SD). Assessments are performed according to RECIST v1.1, PCWG3-modified RECIST v1.1, and RECIP 1.0 by both Independent Central Review (BICR) and Investigator, except for RECIP 1.0 which is evaluated by BICR only. Frequencies, percentages, and two-sided 95% confidence intervals (CIs) for each treatment group will be presented. Between-group comparisons will be performed using a stratified logistic regression model, adjusting for stratification factors (nomogram score [>178 vs. ≤178], ECOG PS [0-1 vs. 2], prior cabazitaxel use, and best supportive care alone). The odds ratio (OR) for the treatment group relative to the control group, along with its two-sided 95% CI and corresponding p-value, will be reported.	Up to 36 months

Collaborators and Investigators

• Sponsor: FutureChem
• Investigators: Principal Investigator: Ji Youl Lee, Seoul St. Mary's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2026
• Primary Completion (Estimated): March 26, 2028
• Study Completion (Estimated): January 26, 2029

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: September 28, 2026
• First Posted (Actual): October 1, 2026

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Neoplasms; Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Prostatic Diseases; Neoplasms by Site; Male Urogenital Diseases; Genital Diseases; Urogenital Diseases
• Additional Relevant MeSH Terms: Genital Diseases, Male; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplasms; Prostatic Neoplasms; Urogenital Neoplasms; Genital Neoplasms, Male; Neoplasms by Site; Male Urogenital Diseases; Prostatic Diseases; Socioeconomic Factors; Population Characteristics; Demography; Family Characteristics; Marital Status; Single Person
• Other Study ID Numbers: FC705-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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