Study of AZD0754 in Participants With Metastatic Prostate Cancer (APOLLO)

• Biological: AZD0754

Inclusion Criteria:

Age

1. Participant must be 18 years or older at the time of signing the informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. form.Type of Participant and Disease Characteristics
2. Participants with:
   1. A histologically confirmed diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of metastatic adenocarcinomacancer arising from mucus-producing glands in organs of the prostate without known neuroendocrine differentiation or small cell features.
   2. Castration-resistant prostate cancer as defined by disease progression despite castration by orchiectomyremoval of one or both testicles, also known as orchidectomy or ongoing luteinising hormone-releasing hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body analogue. Participants receiving medical castration therapy with gonadotropin releasing hormone analogues should continue this treatment during the study.
   3. Measurable PSA >/=1 ng/mL AND
   4. Evidence of progression within 6 months prior to screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening according to one of the following:

   (i) Radiographic disease progression in soft tissuetissue/the material that joins, holds up or surrounds inside body parts such as fat, muscle, ligaments and lining around joints based on Response Evaluation Criteria in Solid Tumours Version 1.1 criteria with or without PSA progression as per Prostate Cancer Working Group Criteria 3 (PCWG3) (ii) Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scana type of medical imaging that uses a radioactive tracer to detect bone conditions or abnormalities as per Prostate Cancer Working Group Criteria 3 (PCWG3).

   (iii) Evidence of disease progression in bone according to PSMA PET scan results in tandem with PSA progression according to PCWG3 criteria.”

3. Participant has previously received a NHA (ie, abiraterone, enzalutamide, apalutamide, darolutamide) and taxane as part of their treatment for prostate cancer (whether before or in the metastatic castration-resistant setting) or be ineligible for or refuse taxanes.
4. For participants with pathogenic mutations in BRCA1 or BRCA2, they must also have received a PARP-inhibitor or be intolerant of this therapy. For participants with non-BRCA HRR deficiency disease, treatment with a PARP-inhibitor is at the discretion of the Investigator based on a riskthe possibility that something bad will happen/benefit analysis and discussion with the participant.
5. For participants who have high microsatellite instability or deficient DNA mismatch repair they must also have received at least one line of checkpoint inhibitors (ie, pembrolizumab), not be eligible for, or be intolerant to therapy as per NCCN or local treatment guidelines.
6. Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status of 0 or 1 prior to apheresisa medical procedure where a machine separates a particular blood compnent from the blood and then returns the rest to the body.
7. Minimum life expectancy of > 12 weeks prior to apheresis in the opinion of the Investigator
8. Adequate organ and marrow function.
9. Consent and provision of tumoura tissue mass that forms from groups of unhealthy cells material to assess STEAP2 expression and other correlative biomarkers retrospectively with pre- and post-treatment biopsies. Fresh baseline and on-treatment biopsies are required unless these are deemed medically unfeasible. If the participant is unable to undergo fresh biopsyremoval of a section of tissue to analyse for cancer cells, an archival tumour sample will be required (age of biopsy cannot be greater than 10 years).