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

Running, not enrolling · Phase 3

Conditions studied: Metastatic Castration-Resistant Prostate Cancer

In brief

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).

Key facts

Study ID

NCT04647526

Run by

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

People needed

455

Starts

2021-02-25

Expected to finish

2028-03-01

Last updated by the study team

2026-01-13

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

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.
• 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.
• 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).
• Albumin ≥30 g/L.
• Human immunodeficiency virus-infected patients who are healthy and have a low risk of acquired immunodeficiency syndrome-related outcomes are included in this trial.
• 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].
• Willing to initiate ARAT therapy (either enzalutamide or abiraterone), pre-specified by investigator, if randomized to Treatment Arm B.
• ECOG performance status 0 to 1.

You may not qualify if…

• Patients are excluded from the study if any of the following criteria apply:
• 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.
• 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.
• 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.
• 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.
• Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer.
• Concurrent illness that may jeopardize the patient's ability to undergo study procedures.
• 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.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.

Where it is running

• 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
• Arizona Institute of Urology (AIU) - Tucson — Tucson, Arizona, United States

Full record on ClinicalTrials.gov

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