Prostate Cancer
Conditions
Brief summary
The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617 that can be given without severe side effects for advanced prostate cancer.
Detailed description
Phase I dose escalation study with 177Lu-PSMA-617 using dose fractionation regimen will be performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu dose \[100 mCi (3.7 GBq) - 600 mCi (22.2 GBq)\] will be escalated in up to 6 different dose levels (3 + 3 study design). Additional 10 subjects will be enrolled at the MTD dose level to further assess safety and tolerability and to obtain a preliminary assessment of efficacy. The study will enroll adult males 18 years of age or older with documented progressive metastatic CRPC. The primary objectives are: - To determine the dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 - To determine the maximal tolerated and recommended phase II dose of 177Lu-PSMA-617 in a 2-week dose-fractionation regimen Subjects will receive the following study interventions: 1. 177Lu-PSMA-617 \[50mCi (1.85GBq) - 300mCi (11.1GBq)\] intravenous X2 doses, 2 weeks apart (Visit 1 and 2) 2. 68Ga-PSMA-HBED-CC \[5 ±2mCi or 185 ±74MBq\] intravenous during screening and at 12 weeks with standard imaging Subjects will be on this study from screening to end of study (day 85). The treatment phase comprises of 8 visits over 12 weeks. Patients will be followed until death for survival assessment. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event. All tests and procedures performed on this study are routine and standard of care except: 68Ga-PSMA-HBED-CC PET/CT scan, administration of investigational agent 177Lu-PSMA-617, research blood samples (CTCs for research, cell-free DNA sample), and PSMA testing on archive tissue.
Interventions
DRUG177Lu-PSMA-617
177Lu-PSMA-617 \[50mCi (1.85GBq) - 300mCi (11.1GBq)\] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)
68Ga-PSMA-HBED-CC \[5 ±2mCi or 185 ±74MBq\] intravenous during screening and at 12 weeks with standard imaging
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed adenocarcinoma of prostate 2. Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: * PSA progression * Objective radiographic progression in soft tissue * New bone lesions 3. ECOG performance status of 0-2 4. Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy. 5. Have previously been treated with at least one of the following: * Androgen receptor signaling inhibitor (such as enzalutamide) * CYP 17 inhibitor (such as abiraterone acetate) 6. Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy. 7. Age \> 18 years 8. Patients must have normal organ and marrow function as defined below: * Absolute neutrophil count \>2,000 cells/mm3 * Hemoglobin ≥9 g/dL (independent of transfusion and/or growth factors within 1 month prior to registration) * Platelet count \>150,000 x 109/uL (independent of transfusion and/or growth factors within 3 months prior to randomization) * Serum creatinine \<1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault * Serum total bilirubin \<1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal * Serum AST and ALT \<1.5 x ULN 9. Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
1. Use of investigational drugs or implantation of investigational medical device ≤4 weeks of Cycle 1, Day 1 or current enrollment in investigational drug or device study 2. Prior systemic beta-emitting bone-seeking radioisotopes 3. Brain metastases or leptomeningeal disease 4. History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry 5. Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study 6. Radiation therapy for treatment of PCa ≤4 weeks of Day 1 Cycle 1 7. Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study. 8. Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration 9. Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse. 10. Known history of known myelodysplastic syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617 | Assessed throughout the DLT period, up to 92 days after starting study drug. | Proportion of subjects experiencing a dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation was assessed. |
| Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617 | from first dose of study drug to at least 12 weeks of subsequent follow-up evaluations, up to 92 days | This outcome is measuring the number of subjects that achieved MTD. MTD is defined as the highest dose level with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. If no DLTs were experienced, then a recommended phase II dose was determined in 2-wk dose-fractionation regimen by using a 3+3 dose escalation design, as no MTD was observed. |
| Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen | Duration of Phase I, up to 47 months | Recommended Phase II dose was determined based on the results of the Phase I portion of the study. Since no Maximum Tolerated Dose was achieved given that no Dose Limiting Toxicities occurred, the Recommended Phase II dose was determined based on the Cohort 5 dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617 | from baseline visit to short term follow up visit, approximately 6 months | Proportion of patients with PSA decline following treatment (fractionated 177Lu-PSMA-617) with the RP2D of fractionated dose 177Lu-PSMA-617 (Phase II). PSA response will be determined by comparing the PSA levels after therapy to the baseline, pre-treatment PSA. |
| Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications | From start of study to progression of disease with at least 12 weeks of subsequent follow-up evaluations, up to 54 months | — |
| Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria | Duration of time on study, from baseline to last follow up visit, up to 54 months | Progression Free Survival, with progression determined based by Radiographic and Biochemical response. Biochemical response was assessed by comparing the PSA levels after therapy to the baseline, pre-treatment PSA. Declines of ≥ 30% confirmed by a second PSA value ≥2 weeks later, are reported. |
| Number of CTC Count Responders | Duration of study, from screening to EOS visit, up to 12 weeks | Changes in CTC count as measured by CellSearch and the rate of favorable CTC count and LDH at 12 weeks following fractionated 177Lu-PSMA-617. All subjects in this study will get blood samples drawn (at screening and EOS visit) for CTC enumeration by CellSearch methodology. Participants whose CTC counts drop to less than 5 or stay below 5 (responders) vs. those who remain at least 5 or above (non-responders) at EOS visit are analyzed. |
| Overall Survival Following Fractionated 177Lu-PSMA-617 | Up to 5 years | Overall survival was defined as the time from start of 177Lu-PSMA-617 to the date of death from any cause, or last date of follow up. |
| Count of Participants That Experience an Adverse Event | From screening to end of study visit, up to 54 months | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORScott Tagawa, MD
Weill Medical College of Cornell University
Participant flow
Recruitment details
Recruitment took place at at Weill Cornell Medicine New York Presbyterian and Tulane Medical Center.
Participants by arm
| Arm | Count |
|---|---|
| 177Lu-PSMA-617 Cohort 1 Cohort 1: Participants were administered of 177Lu-PSMA-617 once at the dose level of 50mCi (1.85GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment | 6 |
| 177Lu-PSMA-617 Cohort 2 Cohort 2: Participants were administered of 177Lu-PSMA-617 once at the dose level of 100mCi (3.7GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment | 6 |
| 177Lu-PSMA-617 Cohort 3 Cohort 3: Participants were administered of 177Lu-PSMA-617 once at the dose level of 200mCi (7.4GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment | 5 |
| 177Lu-PSMA-617 Cohort 4 Cohort 4: Participants were administered of 177Lu-PSMA-617 once at the dose level of 250mCi (9.25GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment | 6 |
| 177Lu-PSMA-617 Cohort 5 Cohort 5: Participants were administered of 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment | 6 |
| Dose Expansion Cohort Participants followed Cohort 5 and were administered 177Lu-PSMA-617 once at the dose level of 300mCi (11.1GBq) via intravenous infusion (IV) in two doses two weeks apart at Visits 1 and 2. Participants were then followed until death for survival assessment. | 21 |
| Total | 50 |
Baseline characteristics
| Characteristic | 177Lu-PSMA-617 Cohort 2 | 177Lu-PSMA-617 Cohort 3 | 177Lu-PSMA-617 Cohort 4 | 177Lu-PSMA-617 Cohort 1 | 177Lu-PSMA-617 Cohort 5 | Dose Expansion Cohort | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 6 Participants | 6 Participants | 3 Participants | 17 Participants | 40 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 6 Participants | 4 Participants | 6 Participants | 19 Participants | 43 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 21 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 6 | 6 / 6 | 5 / 5 | 5 / 6 | 6 / 6 | 19 / 21 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 5 / 5 | 6 / 6 | 6 / 6 | 21 / 21 |
| serious Total, serious adverse events | 1 / 6 | 1 / 6 | 2 / 5 | 1 / 6 | 0 / 6 | 3 / 21 |
Outcome results
Primary
Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617
This outcome is measuring the number of subjects that achieved MTD. MTD is defined as the highest dose level with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. If no DLTs were experienced, then a recommended phase II dose was determined in 2-wk dose-fractionation regimen by using a 3+3 dose escalation design, as no MTD was observed.
Time frame: from first dose of study drug to at least 12 weeks of subsequent follow-up evaluations, up to 92 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 177Lu-PSMA-617 Cohort 1 | Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617 | 0 Participants |
| 177Lu-PSMA-617 Cohort 2 | Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617 | 0 Participants |
| 177Lu-PSMA-617 Cohort 3 | Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617 | 0 Participants |
| 177Lu-PSMA-617 Cohort 4 | Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617 | 0 Participants |
| 177Lu-PSMA-617 Cohort 5 | Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617 | 0 Participants |
| Dose Expansion Cohort | Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617 | 0 Participants |
Primary
Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617
Proportion of subjects experiencing a dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation was assessed.
Time frame: Assessed throughout the DLT period, up to 92 days after starting study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 177Lu-PSMA-617 Cohort 1 | Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617 | 0 Participants |
| 177Lu-PSMA-617 Cohort 2 | Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617 | 0 Participants |
| 177Lu-PSMA-617 Cohort 3 | Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617 | 0 Participants |
| 177Lu-PSMA-617 Cohort 4 | Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617 | 0 Participants |
| 177Lu-PSMA-617 Cohort 5 | Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617 | 0 Participants |
| Dose Expansion Cohort | Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617 | 0 Participants |
Primary
Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen
Recommended Phase II dose was determined based on the results of the Phase I portion of the study. Since no Maximum Tolerated Dose was achieved given that no Dose Limiting Toxicities occurred, the Recommended Phase II dose was determined based on the Cohort 5 dose.
Time frame: Duration of Phase I, up to 47 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 177Lu-PSMA-617 Cohort 1 | Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen | 300 mci |
Secondary
Count of Participants That Experience an Adverse Event
Time frame: From screening to end of study visit, up to 54 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 177Lu-PSMA-617 Cohort 1 | Count of Participants That Experience an Adverse Event | 6 Participants |
| 177Lu-PSMA-617 Cohort 2 | Count of Participants That Experience an Adverse Event | 6 Participants |
| 177Lu-PSMA-617 Cohort 3 | Count of Participants That Experience an Adverse Event | 5 Participants |
| 177Lu-PSMA-617 Cohort 4 | Count of Participants That Experience an Adverse Event | 6 Participants |
| 177Lu-PSMA-617 Cohort 5 | Count of Participants That Experience an Adverse Event | 6 Participants |
| Dose Expansion Cohort | Count of Participants That Experience an Adverse Event | 21 Participants |
Secondary
Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications
Time frame: From start of study to progression of disease with at least 12 weeks of subsequent follow-up evaluations, up to 54 months
Population: Only evaluable subjects were analyzed for this measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 177Lu-PSMA-617 Cohort 1 | Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications | 4 Participants |
| 177Lu-PSMA-617 Cohort 2 | Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications | 0 Participants |
| 177Lu-PSMA-617 Cohort 3 | Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications | 1 Participants |
| 177Lu-PSMA-617 Cohort 4 | Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications | 1 Participants |
| 177Lu-PSMA-617 Cohort 5 | Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications | 1 Participants |
| Dose Expansion Cohort | Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications | 3 Participants |
Secondary
Number of CTC Count Responders
Changes in CTC count as measured by CellSearch and the rate of favorable CTC count and LDH at 12 weeks following fractionated 177Lu-PSMA-617. All subjects in this study will get blood samples drawn (at screening and EOS visit) for CTC enumeration by CellSearch methodology. Participants whose CTC counts drop to less than 5 or stay below 5 (responders) vs. those who remain at least 5 or above (non-responders) at EOS visit are analyzed.
Time frame: Duration of study, from screening to EOS visit, up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 177Lu-PSMA-617 Cohort 1 | Number of CTC Count Responders | 4 Participants |
| 177Lu-PSMA-617 Cohort 2 | Number of CTC Count Responders | 4 Participants |
| 177Lu-PSMA-617 Cohort 3 | Number of CTC Count Responders | 4 Participants |
| 177Lu-PSMA-617 Cohort 4 | Number of CTC Count Responders | 2 Participants |
| 177Lu-PSMA-617 Cohort 5 | Number of CTC Count Responders | 4 Participants |
| Dose Expansion Cohort | Number of CTC Count Responders | 21 Participants |
Secondary
Overall Survival Following Fractionated 177Lu-PSMA-617
Overall survival was defined as the time from start of 177Lu-PSMA-617 to the date of death from any cause, or last date of follow up.
Time frame: Up to 5 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 177Lu-PSMA-617 Cohort 1 | Overall Survival Following Fractionated 177Lu-PSMA-617 | 385 days |
| 177Lu-PSMA-617 Cohort 2 | Overall Survival Following Fractionated 177Lu-PSMA-617 | 607 days |
| 177Lu-PSMA-617 Cohort 3 | Overall Survival Following Fractionated 177Lu-PSMA-617 | 368 days |
| 177Lu-PSMA-617 Cohort 4 | Overall Survival Following Fractionated 177Lu-PSMA-617 | 743 days |
| 177Lu-PSMA-617 Cohort 5 | Overall Survival Following Fractionated 177Lu-PSMA-617 | 409 days |
| Dose Expansion Cohort | Overall Survival Following Fractionated 177Lu-PSMA-617 | 478 days |
Secondary
Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria
Progression Free Survival, with progression determined based by Radiographic and Biochemical response. Biochemical response was assessed by comparing the PSA levels after therapy to the baseline, pre-treatment PSA. Declines of ≥ 30% confirmed by a second PSA value ≥2 weeks later, are reported.
Time frame: Duration of time on study, from baseline to last follow up visit, up to 54 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 177Lu-PSMA-617 Cohort 1 | Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria | 95 days |
| 177Lu-PSMA-617 Cohort 2 | Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria | 147 days |
| 177Lu-PSMA-617 Cohort 3 | Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria | 119 days |
| 177Lu-PSMA-617 Cohort 4 | Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria | 188 days |
| 177Lu-PSMA-617 Cohort 5 | Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria | 99 days |
| Dose Expansion Cohort | Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria | 176 days |
Secondary
The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617
Proportion of patients with PSA decline following treatment (fractionated 177Lu-PSMA-617) with the RP2D of fractionated dose 177Lu-PSMA-617 (Phase II). PSA response will be determined by comparing the PSA levels after therapy to the baseline, pre-treatment PSA.
Time frame: from baseline visit to short term follow up visit, approximately 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 177Lu-PSMA-617 Cohort 1 | The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617 | 5 Participants |
| 177Lu-PSMA-617 Cohort 2 | The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617 | 3 Participants |
| 177Lu-PSMA-617 Cohort 3 | The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617 | 3 Participants |
| 177Lu-PSMA-617 Cohort 4 | The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617 | 6 Participants |
| 177Lu-PSMA-617 Cohort 5 | The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617 | 6 Participants |
| Dose Expansion Cohort | The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617 | 21 Participants |