Study Evaluating mCRPC Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment

NCT04647526 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 5 other identifiers: 27232J5T-OX-JXCAPBP-3012021-002641-152024-515604-39-00
• Study Type: interventional
• Target: 455
• Locations: 6 countries
• Sites: 54

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of \[Lu-177\]-PNT2002 in patients with metastatic castration-resistant prostate cancer who have progressed following treatment with androgen receptor axis-targeted therapy (ARAT).

Conditions

Metastatic Castration-Resistant Prostate Cancer

Keywords

PSMA; mCRPC; Prostate cancer; 177Lu-PSMA; radioligand therapy; PSMA-I&T; SPLASH

Outcome Measures

Primary Outcomes (1)

• Randomization Phase: Radiographic Progression-Free Survival (rPFS)

  * rPFS, as assessed by blinded independent central review (BICR), is the time from the randomization date to progression on soft tissue per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or confirmed progression on bone lesions by Prostate Cancer Working Group 3 (PCWG3) criteria, or death from any cause. * The date of disease progression is the date of the scan for the first objectively documented progressive disease (PD) per RECIST v1.1 or PCWG3. PD is defined as a ≥20% increase in the sum of the diameters of target lesions (≥5 mm absolute), with reference being the smallest sum in the study, or unequivocal progression of non-target lesions, or appearance of new lesions. * Participants who do not progress, including those who started new anticancer therapy, withdrew from the study, or were lost to follow-up without disease progression, were censored at the last valid assessment for RECIST v1.1 or PCWG3.

  From the randomization date to the first documented progressive disease or death from any cause (up to 23 months)

Secondary Outcomes (5)

• Randomization Phase: Percentage of Participants With Objective Response Rate (ORR)

  Randomization until measured progressive disease (up to 23 months)

• Randomization Phase: Duration of Response

  From the date of first CR or PR to disease progression or death (up to 16.3 months)

• Randomization Phase: Percentage of Participants With Prostate-Specific Antigen (PSA) Response Rate

  From the randomization up to 23 months

• Randomization Phase: Biochemical Progression-Free Survival (bPFS)

  From the randomization up to 23 months

• Overall Survival

  5 years

Study Arms (4)

Lead-in Dosimetry Phase: [Lu-177]-PNT2002

EXPERIMENTAL

Participants received 6.8 gigabecquerels (GBq) (±10%) of \[Lu-177\]-PNT2002 by intravenous infusion every 8 weeks for 4 cycles.

Drug: [Lu-177]-PNT2002

Randomization Phase: [Lu-177]-PNT2002 (Arm A)

EXPERIMENTAL

Participants received 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 by intravenous infusion every 8 weeks for 4 cycles.

Drug: [Lu-177]-PNT2002

Randomization Phase: Abiraterone or Enzalutamide (Arm B)

ACTIVE COMPARATOR

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.

Drug: [Lu-177]-PNT2002; Drug: Abiraterone; Drug: Enzalutamide

Pharmacokinetic (PK) Extension Phase: [Lu-177]-PNT2002

EXPERIMENTAL

Participants received 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 by intravenous infusion every 8 weeks for 4 cycles.

Drug: [Lu-177]-PNT2002

Interventions

[Lu-177]-PNT2002 DRUG

Participants randomized to Arm A will receive 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 every 8 weeks for 4 cycles

Also known as: [Lu-177]-PSMA-I&T, LY4187525

Lead-in Dosimetry Phase: [Lu-177]-PNT2002; Pharmacokinetic (PK) Extension Phase: [Lu-177]-PNT2002; Randomization Phase: Abiraterone or Enzalutamide (Arm B); Randomization Phase: [Lu-177]-PNT2002 (Arm A)

Abiraterone DRUG

Abiraterone (1000 mg orally once daily with: 5 mg twice daily prednisone or 0.5 mg once daily dexamethasone)

Randomization Phase: Abiraterone or Enzalutamide (Arm B)

Enzalutamide DRUG

Enzalutamide (160 mg orally once daily)

Randomization Phase: Abiraterone or Enzalutamide (Arm B)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male aged 18 years or older.
• Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
• Ineligible or averse to chemotherapeutic treatment options.
• Patients must have progressive mCRPC at the time of consent based on at least 1 of the following criteria:
• 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.
• 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.
• Progression of bone disease defined as the appearance of two or more new lesions by bone scan.
• Progression on previous treatment with one ARAT (abiraterone or enzalutamide or darolutamide or apalutamide) in either the CSPC or CRPC setting.
• PSMA-PET scan (i.e., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by the sponsor's central reader.
• Castrate circulating testosterone levels (\<1.7 nmol/L or \<50 ng/dL).
• Adequate organ function, independent of transfusion:
• 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.

You may not qualify if:

• Patients are excluded from the study if any of the following criteria apply:
• 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.
• Prior treatment with systemic radionuclides (e.g. radium-223, rhenium-186, strontium 89).
• Prior immuno-therapy, except for sipuleucel-T.
• Prior PSMA-targeted radioligand therapy, e.g., Lu-177-PSMA-617, I 131-1095.
• Prior poly ADP ribose polymerase (PARP) inhibitor for prostate cancer.
• Patients who progressed on 2 or more lines of ARATs.
• Patients receiving bone-targeted therapy (e.g. denosumab, zoledronic acid) not on stable doses for at least 4 weeks prior to randomization.
• Administration of an investigational agent ≤60 days or 5 half-lives, whichever is shorter, prior to randomization.
• Major surgery ≤30 days prior to randomization.
• Estimated life expectancy \<6 months as assessed by the principal investigator.
• Presence of liver metastases \>1 cm on abdominal imaging.
• 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.
• Dose escalation or initiation of opioids for cancer-related pain ≤30 days prior to consent up to and including randomization.
• Known presence of central nervous system metastases.

Sponsors & Collaborators

• POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company: lead

Study Sites (54)

Arizona Institute of Urology (AIU) - Tucson

Tucson, Arizona, 85704, United States

Location

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

VA Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

University of California Los Angeles, Nuclear Medicine Clinic

Los Angeles, California, 90095, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

UC Irvine Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94305, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

Tulane University Medical Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Chesapeake Urology Associates (CUA) P.A.

Towson, Maryland, 21204, United States

Location

University of Michigan Hospitals

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

VA St. Louis Health Care System

St Louis, Missouri, 63106, United States

Location

Saint Louis University Hospital

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Urology Cancer Center, PC

Omaha, Nebraska, 68130, United States

Location

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

Location

New Mexico Oncology Hematology Consultants Ltd., New Mexico Cancer Center

Albuquerque, New Mexico, 87109, United States

Location

New York Presbyterian Hospital/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Tri-State Urologic Services

Cincinnati, Ohio, 45212, United States

Location

Greater Dayton Cancer Center

Kettering, Ohio, 45409, United States

Location

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Dallas VA Medical Center, Nuclear Medicine Service

Dallas, Texas, 75216, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Excel Diagnostics & Nuclear Oncology Center

Houston, Texas, 77402, United States

Location

Swedish Cancer Institute Research

Seattle, Washington, 98104, United States

Location

BC Cancer - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Nova Scotia Health Authority

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

London Health Sciences Center - Victoria Hospital

London, Ontario, N6A 5W9, Canada

Location

Sunnybrook Research Institute, Odette Cancer Center

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - University Hospital of Montreal

Montreal, Quebec, H2X 3E4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

CHU of Quebec - Laval University

Québec, Quebec, G1R 2J6, Canada

Location

Center Jean Perrin, Department of Medical Oncology

Clermont-Ferrand, 63011, France

Location

Claude Huriez Hospital

Lille, 59037, France

Location

Leon Berard Center

Lyon, 69373, France

Location

La Timone Hospital, Nuclear Medicine Department

Marseille, 13385, France

Location

Montpellier Cancer Institute, Department of Nuclear Medicine

Montpellier, 34298, France

Location

Tenon Hospital, Department of Medical Oncology

Paris, 75020, France

Location

St. Antonius Hospital

Nieuwegein, Netherlands

Location

Radboud University Medical Center (Radboudumc)

Nijmegen, Netherlands

Location

Erasmus University Medical Center Rotterdam

Rotterdam, 3015 GD, Netherlands

Location

Sahlgrenska University Hospital

Gothenburg, 41345, Sweden

Location

Norrlands University Hospital, Department of Radiation Sciences, Oncology

Umeå, Sweden

Location

Charing Cross Hospital, Department of Medical Oncology

London, United Kingdom

Location

Royal Marsden NHS Foundation Trust - Institute of Cancer Research

Sutton, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 26795286 BACKGROUND

• 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.

  PMID: 39839782 DERIVED

• 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.

  PMID: 36735603 DERIVED

Related Links

• 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)

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

abiraterone; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

08004595979

Study Officials

• Jessica Jensen

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 1, 2020
• Study Start: February 25, 2021
• Primary Completion: November 1, 2023
• Study Completion (Estimated): March 1, 2028
• Last Updated: January 13, 2026
• Results First Posted: January 13, 2026

Record last verified: 2025-12

Locations

NL (3); SE (2); CA (8); US (33); GB (2); FR (6)