Sacituzumab Tirumotecan in Pts w/ NEPC After Progression on Prior Chemotherapy

Inclusion Criteria 1. Patients with histologically or cytologically confirmed diagnosis of de novo (d-NEPC) or treatment related NEPC (t-NEPC), defined by one or more of the following: histologically small cell prostate cancer or neuroendocrine differentiation by IHC, defined by positive staining by chromogranin or synaptophysin and/or additional neuroendocrine markers. Patients with t-NEPC must have history of treatment with ADT and/or an androgen receptor pathway inhibitor (ARPI) agent. Note: Pure small cell/NEPC or NEPC mixed with adenocarcinoma or other histologic subtype are eligible 2. Patients must have progressed following at least one course (minimum of 4 cycles) of platinum-based chemotherapy (alone or in combination with etoposide or taxane). Patients who received prior taxane alone for treatment of mHSPC or mCRPC, and patients who received a checkpoint inhibitor immunotherapy alone or in combination with prior chemotherapy are eligible. Patients who received a non-ADC drug through a prior clinical trial or Tarlatamab are also eligible provided they had also received at least one course of platinum-based chemotherapy. 3. Patients who have measurable metastatic disease per PCWG modified RECIST 1.1 criteria as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions. Patients with radiologically positive pelvic nodal, bone or soft tissue metastatic disease, are acceptable. Progressive disease is defined per PCWG modified RECIST 1.1 criteria. Note: Patients who have prior prostatectomy, definitive or salvage radiation, are eligible. 4. Male participant at least 18 years of age at the time of providing the informed consent. 5. If capable of producing sperm, the participant agrees to the following during the intervention period and for at least 120 days after: * Refrains from donating sperm * Uses a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant PLUS partner use of an additional contraceptive method (refer to Section 10.4.2), as a condom may break or leak Note: If the participant is azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview), no contraception is required. 6. If capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use a penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate. 7. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. 8. Has provided an archival tumor tissue sample collected within 12 months prior to the enrollment or most recently obtained core, incisional, or excisional biopsy of a tumor lesion from prostate or a metastatic site, from which NEPC was diagnosed. Irradiated tissue is not acceptable. Sites should follow local guidelines regarding fresh tissue collection. 9. Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except for alopecia and vitiligo). Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible. 10. Adequate organ function as defined below. Specimens must be collected within 10 days before the start of study intervention. Any value of serum prostate specific antigen (PSA) is considered eligible. 11. Absolute neutrophil count ≥1500/µL 12. Platelets ≥100,000/µL 13. Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L 14. Creatinine clearance ≥30 mL/min 15. Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN 16. ALT/AST ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) 17. Albumin ≥3.0 g/dLb 18. INR or PT/aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants a Criteria must be met without colony-stimulating factors, erythropoietin dependency, and without pRBC transfusion within the preceding 2 weeks. b Criteria must be met without albumin supplementation within the last 72 hours. 19. Has ECOG performance status of 0 or1 20. Be willing and able to comply with study procedures, laboratory tests, and other requirements of the study. 21. HIV-infected participants must have well-controlled HIV on ART, defined as: * Having a CD4+ T-cell count ≥350 cells/mm3 at the time of screening * Having achieved and maintained virologic suppression, defined as confirmed HIV RNA level below 50 or the LLOQ using the locally available assay, at the time of screening and for at least 12 weeks before screening * Absence of any AIDS-defining opportunistic infections within the past 12 months * Being on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before enrollment and agreeing to continue ART throughout the study Note: The ART regimen must not contain any antiretroviral medications that are strong CYP3A4 inducers/inhibitors/substrates. Refer to https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Please note that this list is not exhaustive and that investigators should review the locally approved label for all concomitant therapy to ensure it is not a strong inducer/inhibitor/substrate of CYP3A4. Note: HIV testing at screening is not required unless there is a known history of HIV infection or it is mandated by local guidelines 22. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load before enrollment. Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention. Hepatitis B testing at screening is not required unless there is a known history of HBV infection or it is mandated by local guidelines 23. Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening. Note: Participants must have completed curative antiviral therapy at least 4 weeks before enrollment. Hepatitis C testing at screening is not required unless there is a known history of HCV infection or it is mandated by local guidelines Exclusion Criteria 1. Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing. 2. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention. 3. Received prior treatment with a TROP2-targeted ADC. 4. Received prior treatment with a topoisomerase 1 inhibitor-containing ADC. 5. Received prior systemic anticancer therapy within 2 weeks before the first dose of study intervention. ADT and/or antiandrogens/ARPI is allowed. 6. Received prior radiotherapy within 2 weeks before the first dose of study intervention, has radiation-related toxicities, requiring corticosteroids, and/or has had radiation pneumonitis. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention. 7. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Refer to Section 6.2 for information on COVID-19 vaccines. 8. Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks. Note: A list of strong inducers/inhibitors of CYP3A4 can be found at the following website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Please note that this list is not exhaustive and that investigators should review the locally approved label for all concomitant therapy to ensure it is not a strong inducer/inhibitor of CYP3A4. 9. Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anticancer therapy is prohibited. 10. Has received an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention. 11. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (excluding carcinoma in situ of the bladder) who have undergone potentially curative resection are not excluded. Note: Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded. 12. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously-treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable, and have not required steroid treatment for at least 14 days before the first dose of study intervention. 13. Has an active infection requiring systemic therapy (except those permitted per Section 5.1) 14. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the individual's ability to cooperate with the requirements of the study, or interfere with the individual's participation for the full duration of the study, such that it is not in the best interest of the individual to participate, in the opinion of the treating investigator. 15. Severe hypersensitivity (Grades ≥3) to study intervention, any of their excipients, and/or to another biologic therapy. 16. Has had major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention. Anticipation of the need for major surgery during the course of treatment with study intervention is also exclusionary. Note: Participants who underwent major surgery must have adequately recovered from toxicity and/or complications from the surgery before starting study intervention. 17. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 18. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc), any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen. 19. Has a "superscan" bone scan. This is defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated.