Ensayos clínicos

Inclusion Criteria:

• Subject has provided informed consent prior to initiation of any study specific  activities/procedures.  
• Men aged ≥ 18 years at time of signing the informed consent.
• Metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC) defined by histological, immunohistochemistry, or genomic analyses of baseline tumor tissue  (by local assessment) or circulating tumor DNA (ctDNA) (by local assessment) as per protocol.
• At least 1 line of prior systemic treatment per protocol. Exception: Subjects may also be included if the aforementioned therapeutic options were medically not appropriate for them.
• For subjects with treatment-emergent NEPC or de novo NEPC with histologic evidence of  prostate cancer with neuroendocrine differentiation.  
• Subjects with treatment-emergent NEPC or de novo NEPC with histologic evidence of  prostate cancer with neuroendocrine differentiation without a history of bilateral  orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH)  analogue therapy during the course of protocol therapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Prostate Cancer Working Group 3 (PCWG3) modifications.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Subjects with treated brain metastases are eligible provided they meet defined criteria.
• Adequate organ function as defined in protocol.

Exclusion Criteria:  

• History of other malignancy within the past 2 years, with exceptions:  
  • Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician;
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
  • Adequately treated non-muscle invasive urothelial carcinoma.
• History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years.
• Untreated (includes new lesions or progression in previously treated lesions) or symptomatic brain metastases and leptomeningeal disease.
• History or presence of relevant CNS pathology such as uncontrolled epilepsy or seizure disorder, aphasia, paresis, dementia, severe brain injuries, Parkinson’s disease, cerebellar disease, organic brain disorder, or psychosis.
• Myocardial infarction within 12 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or clinically significant uncontrolled cardiac arrhythmia.
• History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 12 months of first dose of tarlatamab.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (prednisone dose > 10 mg per day or equivalent dose) or any other form of immunosuppressive therapy within 7 days prior study day 1.
• Active autoimmune disease requiring systemic treatment within the past 2 years (i.e., with the use of disease modifying agents, non-physiologic doses of corticosteroids or immunosuppressive drugs); including current autoimmune sequelae or previous Grade > 2 autoimmune sequelae from checkpoint inhibitors or other immunomodulatory treatments that require systemic therapy.
  • Exception: Participants with autoimmune endocrine disorders on hormonal supplementation may be enrolled even if  > Grade 2 when it first occurred, if approved by the Medical Monitor.
• Active infection requiring oral or IV antimicrobials for management within 7 days of first dose tarlatamab.
• Exclusion of hepatitis infection based on the following results and/or criteria:
  • Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic Hepatitis B or recent acute hepatitis B);
  • Negative HepBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B;
  • Positive Hepatitis C virus antibody: Hepatitis C virus RNA by PCR is necessary. Detectable Hepatitis C virus RNA suggests chronic hepatitis C.
• Known positive test for human immunodeficiency virus (HIV).
• Anti-tumor therapy within 28 days of study day 1; concurrent use of hormone deprivation therapy for hormone-refractory prostate is permitted; subjects on a stable bisphosphonate or denosumab for ≥ 30 days prior to study day 1 are eligible.
• Exceptions:
  • Subjects who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicities have resolved to Grade ≤ 1;
  • Prior palliative radiotherapy must have been completed at least 7 days before the first dose of tarlatamab;
  • Subjects who received androgen signaling inhibitor (e.g., abiraterone, enzalutamide, and/or apalutamide) are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to Grade ≤ 1
• Major surgical procedures ≤ 28 days or non–study-related minor procedures ≤ 7 days prior to study day 1. In all cases, the subjects must be sufficiently recovered and stable before treatment administration
• Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded with the exception of 68-Gallium-prostate-specific membrane antigen-11 (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) and fluorodeoxyglucose (18F-FDG) PET/CT.
• Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia or toxicities that are stable and well-controlled and there is agreement to allow by the investigator and sponsor
• Subject unable to receive both iodinated contrast for CT scans and gadolinium contrast for magnetic resonance imaging (MRI) scans.
• Subject has known sensitivity and immediate hypersensitivity to any components of tarlatamab.
• Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator’s knowledge
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
• Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an 132 days after the last dose of tarlatamab. 
• Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for 132 days after the last dose of tarlatamab.
• Male subjects unwilling to abstain from donating sperm during treatment and for 132 days after the last dose of tarlatamab.
• Subjects on prior DLL3-targeted therapy may be eligible if discussed with Amgen medical monitor prior to enrollment
• History of hypophysitis or pituitary dysfunction.
• Subjects of child-bearing potential who are not willing to practice an acceptable method(s) of effective birth control while on study through 35 days after receiving last dose of AMG 757. Acceptable methods of effective birth control include sexual abstinence; vasectomy; or a condom with spermicide.