Expanded Access Treatment with [Lu-177]-PNT2002 for Adult Patients with Prostate-Specific Membrane Antigen (PSMA)-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Inclusion Criteria

• •1. Patient is male aged 18 years or older;
• •2. Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate;
• •3. Patients must have at least 1 metastatic lesion present on CT, MRI, or bone scan imaging;
• •4. Patients must have progressive mCRPC 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 diameters (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 2 or more lesions by bone scan
• •5. Progression on prior treatment with ≥1 ARPI (abiraterone, apalutamide, darolutamide, enzalutamide ) in nmCRPC, mHSPC or mCRPC;
• •6. PSMA-PET scan (\[Ga-68\]-PSMA-11 or \[F-18\]-DCFPyL) positive as determined by local investigator;
• •1. At least 1 PSMA-PET positive lesion for prostate cancer
• •2. Uptake greater than the liver will be used as the reference for determining PSMA-PET positivity and uptake less than or equal to the liver will be used as the reference for determining PSMA-PET negativity
• •3. All lymph nodes that measure ≥25 mm in short axis on anatomic imaging must be PSMA-PET positive
• •4. All bone metastases with soft tissue component(s) ≥10 mm in short axis must be PSMA-PET positive (PSMA-negative osseous metastases without a soft tissue component do not exclude patients)
• •5. All solid organ metastases (i.e., lung, liver, adrenal glands, etc.) ≥10 mm in short axis must be PSMA-PET positive
• •7. Castrate levels of circulating testosterone (\<1.7 nmol/L or \<50 ng/dL);
• •8. Patients must have recovered to Grade ≤2 from all clinically significant toxicities related to; prior therapies (i.e., prior ARPI, chemotherapy, PARPi, radioisotope or immunotherapy, etc.)
• •9. Adequate organ function, independent of transfusion;
• •a. Bone marrow reserve
• •i. White blood cell (WBC) count ≥2.5 x 109/L OR absolute neutrophil count (ANC) ≥1.5 x 109/L ii. Platelets ≥100 x 109/L iii. Hemoglobin ≥80 g/L or ≥8 g/dL
• •b. Liver function
• •i. Total bilirubin ≤1.5 x institutional upper limit of normal (ULN). For patients with known Gilbert's syndrome, ≤3.0 x ULN ii. ALT and AST ≤3.0 x ULN
• •c. Renal function
• •i. Creatinine clearance ≥50 mL/min based on Cockroft-Gault formula
• •d. Albumin ≥30 g/L
• •10. Human immunodeficiency virus-infected patients who are healthy and have a low risk of acquired immunodeficiency syndrome-related outcomes are eligible;
• •11. ECOG performance status 0 or 1;
• •12. 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 \[periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of abstinence\].
• •13. Signed Informed Consent Form
• •5. Symptomatic cord compression, or clinical radiologic findings indicative of impending cord compression;
• •6. Any pre-existing symptoms, or concurrent severe and/or uncontrolled medical conditions such as ureteral obstruction, which in the opinion of the investigator would compromise safe participation in the \[Lu-177\]-PNT2002 EAP;
• •7. Not able to understand and comply with treatment instructions and requirements;