The goal of this clinical trial is to evaluate the safety of the combination therapy of Lutetium (177Lu) DGUL and pembrolizumab. It will also assess the antitumor efficacy and pharmacokinetics of the combination therapy compared to Lutetium (177Lu) DGUL monotherapy. Participants will: Monotherapy: Receive Lutetium (177Lu) DGUL 4 times (plus 2 additional doses) at 6-week intervals Combination therapy: Receive Lutetium (177Lu) DGUL 4 times (plus 2 additional doses) at 6-week intervals along with pembrolizumab up to 18 times at 6-week intervals
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Lutetium (177Lu) DGUL will be administered in 4 doses at 6-week intervals (Q6W), and for patients showing good tolerance, additional 2 doses may be added, for a maximum of 6 doses.
Pembrolizumab will be introduced at a dose of 400 mg every 6 weeks, beginning with the second cycle of Lutetium (177Lu) DGUL, and will continue for up to approximately 2 years (18 doses).
Number of patients with treatment-emergent adverse events (TEAEs)
Time frame: From enrollment to 6-month follow-up after the end of treatment
Number of patients with drug-related TEAEs
Time frame: From enrollment to 6-month follow-up after the end of treatment
Adverse events (AEs)
Time frame: From enrollment to 6-month follow-up after the end of treatment
Drug-related adverse reactions based on dose limited toxicity (DLT) definitions
Time frame: From enrollment to 6-month follow-up after the end of treatment
Radiographic progression-free survivla (rPFS)
Time frame: From enrollment to 6-month follow-up after the end of treatment
1-year overall survivla (OS)
Time frame: From enrollment to 6-month follow-up after the end of treatment
Objective response rate (ORR; confirmed complete response (CR) + partial response (PR))
Time frame: From enrollment to 6-month follow-up after the end of treatment
Prostate specific antigen (PSA) response rate (>50% decrease compared to baseline PSA)
Time frame: From enrollment to 6-month follow-up after the end of treatment
PSA PFS
Time frame: From enrollment to 6-month follow-up after the end of treatment
Best PSA response through waterfall plot
Time frame: From enrollment to 6-month follow-up after the end of treatment
Disease control rate (DCR)
Time frame: From enrollment to 6-month follow-up after the end of treatment
Duration of response (DOR)
Time frame: From enrollment to 6-month follow-up after the end of treatment
Tumor change rate (target lesion) through waterfall plot
Time frame: From enrollment to 6-month follow-up after the end of treatment
Pain severity (numeric rating scale, NRS) and opioid analgesic use
Time frame: From enrollment to 6-month follow-up after the end of treatment
Quality of Life Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
The EORTC QLQ-C30 measures global health status, functional scales, and symptom scales. All scores range from 0 to 100. For functional and global health scales, higher scores indicate better functioning. For symptom scales, higher scores indicate worse symptoms.
Time frame: From enrollment to 6-month follow-up after the end of treatment
Quality of Life Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Prostate Cancer Module (EORTC QLQ-PR25)
The EORTC QLQ-PR25 assesses urinary, bowel, hormonal treatment-related symptoms and sexual functioning. Scores range from 0 to 100. For symptom scales, higher scores indicate worse symptoms. For sexual functioning, higher scores indicate better functioning.
Time frame: From enrollment to 6-month follow-up after the end of treatment
Quality of Life Assessed by the EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L)
The EQ-5D-5L generates an index value reflecting health status, typically ranging from less than 0 (worse than death) to 1 (full health). Higher scores indicate better overall health. A Visual Analog Scale (0-100) may also be reported, where higher scores indicate better self-rated health.
Time frame: From enrollment to 6-month follow-up after the end of treatment
Time-Activity Curve for Lutetium (177Lu) DGUL
The time-activity curve will be generated using serial imaging to quantify radioactivity kinetics of Lutetium (177Lu) DGUL in target tissues. Activity is measured in megabecquerels (MBq) over time.
Time frame: Dosimetry of Lutetium (¹⁷⁷Lu) DGUL could have a time frame of "0, 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 120 hours post-dose
Cumulative Activity of Lutetium (177Lu) DGUL
Cumulative activity represents the total integrated activity (MBq·h) within organs or lesions over time, derived from the time-activity curve.
Time frame: Dosimetry of Lutetium (¹⁷⁷Lu) DGUL could have a time frame of "0, 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 120 hours post-dose
Residence Time of Lutetium (177Lu) DGUL
Residence time is the time-integrated activity coefficient describing the average time (hours) that Lutetium (177Lu) DGUL remains in specific organs or lesions.
Time frame: Dosimetry of Lutetium (¹⁷⁷Lu) DGUL could have a time frame of "0, 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 120 hours post-dose
Effective Dose of Lutetium (177Lu) DGUL
The effective dose will be calculated using organ residence times and standard dosimetry models. Effective dose is reported in millisieverts (mSv).
Time frame: Dosimetry of Lutetium (¹⁷⁷Lu) DGUL could have a time frame of "0, 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 120 hours post-dose
Area Under the Plasma Concentration-Time Curve (AUC) of Lutetium (177Lu) DGUL
AUC represents the total systemic exposure to Lutetium (177Lu) DGUL over time. Reported in MBq·h or ng·h/mL depending on analytical method.
Time frame: Dosimetry of Lutetium (¹⁷⁷Lu) DGUL could have a time frame of "0, 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 120 hours post-dose
Peak Plasma Concentration (Cmax) of Lutetium (177Lu) DGUL
Cmax is the highest observed plasma concentration of Lutetium (177Lu) DGUL. Reported in MBq/mL or ng/mL.
Time frame: Dosimetry of Lutetium (¹⁷⁷Lu) DGUL could have a time frame of "0, 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 120 hours post-dose
Time to Peak Plasma Concentration (Tmax) of Lutetium (177Lu) DGUL
Tmax is the time at which Cmax occurs. Reported in hours.
Time frame: Dosimetry of Lutetium (¹⁷⁷Lu) DGUL could have a time frame of "0, 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 120 hours post-dose
Elimination Half-Life (T1/2) of Lutetium (177Lu) DGUL
T1/2 represents the time required for the plasma concentration of Lutetium (177Lu) DGUL to decrease by 50%. Reported in hours.
Time frame: Dosimetry of Lutetium (¹⁷⁷Lu) DGUL could have a time frame of "0, 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 120 hours post-dose
Volume of Distribution (Vd) of Lutetium (177Lu) DGUL
Vd is the apparent volume in which Lutetium (177Lu) DGUL is distributed throughout the body. Reported in liters (L).
Time frame: Dosimetry of Lutetium (¹⁷⁷Lu) DGUL could have a time frame of "0, 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 120 hours post-dose
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