Treatment of Patients With Progressive mCRPC With 177Lu-PSMA-617

The purpose of this study is to evaluate the safety and tolerability of Lutetium-177-PSMA-617 (PLUVICTO) in patients with metastatic castration-resistant prostate cancer (mCRPC) and extensive bone metastases, which appear as a "super scan" pattern on a bone scan. Pluvicto is FDA-approved, but patients with super scan bone scans were previously excluded from the VISION clinical trial, leaving a knowledge gap. The study will enroll up to 30 men with metastatic castration-resistant prostate cancer, with an initial dosing approach that differs from the standard dose. The safety and tolerability of PLUVICTO will be evaluated in this study, with a focus on identifying the optimal dose for this population. This study addresses an important gap in understanding how Pluvicto performs in mCRPC patients with super scan findings.

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

1. Ability to understand and sign an informed consent form (ICF).
2. Willingness and ability to comply with study requirements.
3. Age ≥18 years.
4. Presence of skeletal metastases with a superscan pattern on a 99mTc-MDP/HDP bone scan, defined by significantly increased skeletal radioisotope uptake relative to soft tissues and faint or absent renal activity.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
6. Hemoglobin ≥9.0 g/dL.
7. Platelet count ≥90 × 10⁹/L.
8. White blood cell count ≥2.0 × 10⁹/L, absolute neutrophil count (ANC) \>1.5 × 10⁹/L.

   o These hematologic criteria must be met without recent transfusions (within 28 days prior to the first study treatment) or growth factor support (within 21 days).
9. Serum/plasma creatinine ≤1.5 × upper limit of normal (ULN).
10. Histological, pathological, or cytological confirmation of prostate cancer.
11. Positive PSMA PET/CT scan showing at least one PSMA-positive metastatic lesion.
12. Castrate-level serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L).
13. Prior treatment with at least one androgen receptor-axis-targeted therapy (ARAT).

Exclusion Criteria:

1. Prior treatment with radiopharmaceuticals (e.g., Strontium-89, Samarium-153, Rhenium- 186, Rhenium-188, Radium-223, hemi-body irradiation) within six months before start of treatment under this protocol.
2. Prior PSMA-targeted radioligand therapy.
3. Systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy, monoclonal antibodies) within four weeks before screening visit.
4. Known hypersensitivity to PLUVICTO or its components.
5. Concurrent treatment with other cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
6. Renal impairment (estimated glomerular filtration rate \<60 mL/min), hemoglobin \<9 g/dL, ANC \<1.5 × 10⁹/L, or platelets \< 90 × 10⁹/L.
7. History of CNS metastases unless treated and stable for 6 months, with no ongoing corticosteroid use.
8. Symptomatic or impending spinal cord compression.
9. Other malignancies impacting life expectancy or interfering with study assessments. Exceptions include non-melanoma skin cancer or superficial bladder cancer that has been adequately treated.
10. Major surgery within 30 days prior to enrollment.
11. Plans to conceive or father a child during treatment and up to six months post-treatment.

• BACKGROUNDHartrampf PE, Weinzierl FX, Buck AK, Rowe SP, Higuchi T, Seitz AK, Kubler H, Schirbel A, Essler M, Bundschuh RA, Werner RA. Matched-pair analysis of [177Lu]Lu-PSMA I&T and [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2022 Jul;49(9):3269-3276. doi: 10.1007/s00259-022-05744-6. Epub 2022 Mar 4. PMID 35243517
• BACKGROUNDEisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. PMID 19097774
• BACKGROUNDBanerjee SR, Pullambhatla M, Byun Y, Nimmagadda S, Green G, Fox JJ, Horti A, Mease RC, Pomper MG. 68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer. J Med Chem. 2010 Jul 22;53(14):5333-41. doi: 10.1021/jm100623e. PMID 20568777
• BACKGROUNDHope TA, Abbott A, Colucci K, Bushnell DL, Gardner L, Graham WS, Lindsay S, Metz DC, Pryma DA, Stabin MG, Strosberg JR. NANETS/SNMMI Procedure Standard for Somatostatin Receptor-Based Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE. J Nucl Med. 2019 Jul;60(7):937-943. doi: 10.2967/jnumed.118.230607. PMID 31263080
• BACKGROUNDAhmadzadehfar H, Eppard E, Kurpig S, Fimmers R, Yordanova A, Schlenkhoff CD, Gartner F, Rogenhofer S, Essler M. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget. 2016 Mar 15;7(11):12477-88. doi: 10.18632/oncotarget.7245. PMID 26871285
• BACKGROUNDMessiou C, Cook G, deSouza NM. Imaging metastatic bone disease from carcinoma of the prostate. Br J Cancer. 2009 Oct 20;101(8):1225-32. doi: 10.1038/sj.bjc.6605334. Epub 2009 Sep 29.