Study Evaluating mCRPC Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment
NCT ID: NCT04647526
Last Updated: 2026-01-13
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE3
455 participants
INTERVENTIONAL
2021-02-25
2028-03-31
Brief Summary
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Detailed Description
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The study consists of 3 phases: Dosimetry, Randomized Treatment, and Long term Follow up.
The study will commence with a 25-patient safety and dosimetry lead-in (Part 1) and proceed to a randomization treatment phase in approximately 390 patients (Part 2). Patients in Part 2 will be randomized in a 2:1 ratio to receive either \[Lu-177\]-PNT2002 (Arm A), or enzalutamide or abiraterone (Arm B). Patients in Arm B who experience radiographic progression per central review and meet protocol defined eligibility, may crossover to receive \[Lu-177\]-PNT2002. After final overall survival (OS) analysis, all patients will continue to be followed through Continued Access, including long-term follow-up (LTFU) for at least 5 years from the first therapeutic dose, death, or loss to follow up (Part 3).
Only patients that meet PSMA PET avidity criteria per central review will be eligible for this study.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Lead-in Dosimetry Phase: [Lu-177]-PNT2002
Participants received 6.8 gigabecquerels (GBq) (±10%) of \[Lu-177\]-PNT2002 by intravenous infusion every 8 weeks for 4 cycles.
[Lu-177]-PNT2002
Participants randomized to Arm A will receive 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 every 8 weeks for 4 cycles
Randomization Phase: [Lu-177]-PNT2002 (Arm A)
Participants received 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 by intravenous infusion every 8 weeks for 4 cycles.
[Lu-177]-PNT2002
Participants randomized to Arm A will receive 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 every 8 weeks for 4 cycles
Randomization Phase: Abiraterone or Enzalutamide (Arm B)
Participants received either of below treatments until radiographic progression.
* Enzalutamide 160 milligram (mg) orally once daily (or)
* Abiraterone 1000 mg orally once daily coadministered with prednisone 5 mg orally twice daily or dexamethasone 0.5 mg orally once daily.
Participants who experienced radiographic progression per Blinded Independent Central Review (BICR) (or after final overall survival (OS), per local investigator-assessment), had not started an intervening treatment, and had no uncontrolled adverse events (AEs) were eligible to consent to cross over to receive 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 intravenous infusion every 8 weeks for 4 cycles.
[Lu-177]-PNT2002
Participants randomized to Arm A will receive 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 every 8 weeks for 4 cycles
Abiraterone
Abiraterone (1000 mg orally once daily with: 5 mg twice daily prednisone or 0.5 mg once daily dexamethasone)
Enzalutamide
Enzalutamide (160 mg orally once daily)
Pharmacokinetic (PK) Extension Phase: [Lu-177]-PNT2002
Participants received 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 by intravenous infusion every 8 weeks for 4 cycles.
[Lu-177]-PNT2002
Participants randomized to Arm A will receive 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 every 8 weeks for 4 cycles
Interventions
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[Lu-177]-PNT2002
Participants randomized to Arm A will receive 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 every 8 weeks for 4 cycles
Abiraterone
Abiraterone (1000 mg orally once daily with: 5 mg twice daily prednisone or 0.5 mg once daily dexamethasone)
Enzalutamide
Enzalutamide (160 mg orally once daily)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
3. Ineligible or averse to chemotherapeutic treatment options.
4. Patients must have progressive mCRPC at the time of consent based on at least 1 of the following criteria:
1. Serum/plasma PSA progression defined as increase in PSA greater than 25% and \>2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart.
2. Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or a new lesion.
3. Progression of bone disease defined as the appearance of two or more new lesions by bone scan.
5. Progression on previous treatment with one ARAT (abiraterone or enzalutamide or darolutamide or apalutamide) in either the CSPC or CRPC setting.
6. PSMA-PET scan (i.e., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by the sponsor's central reader.
7. Castrate circulating testosterone levels (\<1.7 nmol/L or \<50 ng/dL).
8. Adequate organ function, independent of transfusion:
1. Bone marrow reserve:
* i. White blood cell (WBC) count ≥2.5 × 10\^9/L OR absolute neutrophil count (ANC) ≥1.5 × 10\^9/L.
* ii. Platelets ≥100 × 10\^9/L.
* iii. Hemoglobin ≥8 mmol/L.
2. Liver function:
* i. Total bilirubin ≤1.5 × institutional upper limit of normal (ULN). For patients with known Gilbert's syndrome, ≤3 × ULN is permitted.
* ii. ALT or AST ≤3.0× ULN.
3. Renal function:
* i. Serum/plasma creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min based on Cockcroft-Gault formula (for patients in France, serum/plasma creatinine ≤1.5 × ULN or CrCl ≥60 mL/min based on Cockcroft-Gault formula).
4. Albumin ≥30 g/L.
9. Human immunodeficiency virus-infected patients who are healthy and have a low risk of acquired immunodeficiency syndrome-related outcomes are included in this trial.
10. For patients who have partners who are pregnant or of childbearing potential: a condom is required along with a highly effective contraceptive method during the study and for 6 months after last study drug administration. Such methods deemed highly effective include a) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, b) progestogen-only hormonal contraception associated with inhibition of ovulation, c) intrauterine device (IUD), d) intrauterine hormone-releasing system (IUS), e) bilateral tubal occlusion, f) vasectomy, g) true sexual abstinence: when this is in line with the preferred and usual lifestyle of the subject \[periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of abstinence\].
11. Willing to initiate ARAT therapy (either enzalutamide or abiraterone), pre-specified by investigator, if randomized to Treatment Arm B.
12. ECOG performance status 0 to 1.
13. Willing and able to comply with all study requirements and treatments (including 177Lu PNT2002) as well as the timing and nature of required assessments.
14. Signed informed consent.
Exclusion Criteria
1. If noted in pathology report, prostate cancer with known significant (\>10% present in cells) sarcomatoid or spindle cell or neuroendocrine components. Any small cell component in the cancer should result in exclusion.
2. Prior treatment for prostate cancer ≤28 days prior to randomization, with the exclusion of first-line local external beam, ARAT, luteinizing hormone-releasing hormone (LHRH) therapy, or non-radioactive bone-targeted agents.
3. Any prior cytotoxic chemotherapy for CRPC (e.g., cabazitaxel or docetaxel); chemotherapy for hormone-sensitive prostate cancer (HSPC) is allowed if the last dose was administered \>1 year prior to consent.
4. Prior treatment with systemic radionuclides (e.g. radium-223, rhenium-186, strontium 89).
5. Prior immuno-therapy, except for sipuleucel-T.
6. Prior PSMA-targeted radioligand therapy, e.g., Lu-177-PSMA-617, I 131-1095.
7. Prior poly ADP ribose polymerase (PARP) inhibitor for prostate cancer.
8. Patients who progressed on 2 or more lines of ARATs.
9. Patients receiving bone-targeted therapy (e.g. denosumab, zoledronic acid) not on stable doses for at least 4 weeks prior to randomization.
10. Administration of an investigational agent ≤60 days or 5 half-lives, whichever is shorter, prior to randomization.
11. Major surgery ≤30 days prior to randomization.
12. Estimated life expectancy \<6 months as assessed by the principal investigator.
13. Presence of liver metastases \>1 cm on abdominal imaging.
14. A superscan on bone scan defined as a bone scan that demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint genitourinary tract activity.
15. Dose escalation or initiation of opioids for cancer-related pain ≤30 days prior to consent up to and including randomization.
16. Known presence of central nervous system metastases.
17. Contraindications to the use of planned ARAT therapy, \[Ga-68\]-PSMA-11, \[F-18\]-DCFPyL or \[Lu-177\]-PNT2002 therapy, including but not limited to the following:
* Hypersensitivity to \[Ga-68\]-PSMA-11, \[F-18\]-DCFPyL or \[Lu-177\]-PNT2002 excipients (Diethylenetriaminepentaacetic acid (DTPA), Sodium ascorbate, Lascorbic acid, Sodium gentisate, HCl, Sodium hydroxide).
* Recent myocardial infarction or arterial thrombotic events (in the past 6 months) or unstable angina (in the past 3 months), bradycardia or left ventricular ejection fraction measurement of \< 50%.
* History of seizures in patients planned to receive enzalutamide.
18. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer.
19. Concurrent illness that may jeopardize the patient's ability to undergo study procedures.
20. Serious psychological, familial, sociological, or geographical condition that might hamper compliance with the study protocol and follow-up schedule. Patients that travel need to be capable of repeated visits even if they are on the control arm.
21. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
22. Concurrent serious (as determined by the investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure (see 12.1 Appendix 1), unstable ischemia, uncontrolled symptomatic arrhythmia, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
18 Years
MALE
No
Sponsors
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POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company
INDUSTRY
Responsible Party
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Principal Investigators
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Jessica Jensen
Role: STUDY_DIRECTOR
Eli Lilly and Company
Locations
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Arizona Institute of Urology (AIU) - Tucson
Tucson, Arizona, United States
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, United States
VA Greater Los Angeles Healthcare System
Los Angeles, California, United States
University of California Los Angeles, Nuclear Medicine Clinic
Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States
UC Irvine Chao Family Comprehensive Cancer Center
Orange, California, United States
Stanford Cancer Institute
Palo Alto, California, United States
University of Colorado Hospital
Aurora, Colorado, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States
Tulane University Medical Center
New Orleans, Louisiana, United States
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States
Chesapeake Urology Associates (CUA) P.A.
Towson, Maryland, United States
University of Michigan Hospitals
Ann Arbor, Michigan, United States
Karmanos Cancer Center
Detroit, Michigan, United States
VA St. Louis Health Care System
St Louis, Missouri, United States
Saint Louis University Hospital
St Louis, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Urology Cancer Center, PC
Omaha, Nebraska, United States
Astera Cancer Care
East Brunswick, New Jersey, United States
New Mexico Oncology Hematology Consultants Ltd., New Mexico Cancer Center
Albuquerque, New Mexico, United States
New York Presbyterian Hospital/Weill Cornell Medical Center
New York, New York, United States
Tri-State Urologic Services
Cincinnati, Ohio, United States
Greater Dayton Cancer Center
Kettering, Ohio, United States
Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
Dallas VA Medical Center, Nuclear Medicine Service
Dallas, Texas, United States
UT Southwestern Medical Center
Dallas, Texas, United States
Excel Diagnostics & Nuclear Oncology Center
Houston, Texas, United States
Swedish Cancer Institute Research
Seattle, Washington, United States
BC Cancer - Vancouver
Vancouver, British Columbia, Canada
Nova Scotia Health Authority
Halifax, Nova Scotia, Canada
London Health Sciences Center - Victoria Hospital
London, Ontario, Canada
Sunnybrook Research Institute, Odette Cancer Center
Toronto, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
CHUM - University Hospital of Montreal
Montreal, Quebec, Canada
Jewish General Hospital
Montreal, Quebec, Canada
CHU of Quebec - Laval University
Québec, Quebec, Canada
Center Jean Perrin, Department of Medical Oncology
Clermont-Ferrand, , France
Claude Huriez Hospital
Lille, , France
Leon Berard Center
Lyon, , France
La Timone Hospital, Nuclear Medicine Department
Marseille, , France
Montpellier Cancer Institute, Department of Nuclear Medicine
Montpellier, , France
Tenon Hospital, Department of Medical Oncology
Paris, , France
St. Antonius Hospital
Nieuwegein, , Netherlands
Radboud University Medical Center (Radboudumc)
Nijmegen, , Netherlands
Erasmus University Medical Center Rotterdam
Rotterdam, , Netherlands
Sahlgrenska University Hospital
Gothenburg, , Sweden
Norrlands University Hospital, Department of Radiation Sciences, Oncology
Umeå, , Sweden
Charing Cross Hospital, Department of Medical Oncology
London, , United Kingdom
Royal Marsden NHS Foundation Trust - Institute of Cancer Research
Sutton, , United Kingdom
Countries
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References
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Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, Schottelius M, Mueller D, Klette I, Wester HJ. 177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy. J Nucl Med. 2016 Jul;57(7):1006-13. doi: 10.2967/jnumed.115.168443. Epub 2016 Jan 21.
Hansen AR, Probst S, Beauregard JM, Viglianti BL, Michalski JM, Tagawa ST, Sartor O, Tutrone RF, Oz OK, Courtney KD, Delpassand ES, Nordquist LT, Osman MM, Chi KN, Sparks R, George N, Hawley SM, Wu W, Jensen JD, Fleshner NE. Initial clinical experience with [177Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer: dosimetry, safety, and efficacy from the lead-in cohort of the SPLASH trial. Front Oncol. 2025 Jan 7;14:1483953. doi: 10.3389/fonc.2024.1483953. eCollection 2024.
American College of Nuclear Medicine (ACNM) 2022 ACNM Annual Meeting AbstractsJanuary 27-29, 2022 Virtual Meeting. Clin Nucl Med. 2023 Feb 3:e246-e277. doi: 10.1097/RLU.0000000000004535. Online ahead of print. No abstract available.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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1400P - Efficacy and safety of 177Lu-PNT2002 prostate-specific membrane antigen (PSMA) therapy in metastatic castration resistant prostate cancer (mCRPC): Initial results from SPLASH
ESMO 2024: Efficacy of 177Lu-PNT2002 in PSMA-Positive mCRPC Following Progression on an Androgen-Receptor Pathway Inhibitor (SPLASH)
Other Identifiers
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J5T-OX-JXCA
Identifier Type: OTHER
Identifier Source: secondary_id
PBP-301
Identifier Type: OTHER
Identifier Source: secondary_id
2021-002641-15
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2024-515604-39-00
Identifier Type: CTIS
Identifier Source: secondary_id
27232
Identifier Type: -
Identifier Source: org_study_id
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