Prostate Cancer
Conditions
Interventions
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent and complying to the study protocol. 2. Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form. 3. 18 years or more of age at the time of signing the informed consent form. 4. Participants with: 1. Histologically confirmed diagnosis of metastatic adenocarcinoma of the prostate 2. Surgically or medically castrated, with serum testosterone levels 50 ng/dL or less (1.75 nmol/L or less) 28 days or less before first dose of study intervention. Participants without prior surgical castration must be currently taking and willing to continue LHRH agonist or antagonist therapy throughout the duration of the study intervention. 3. Castration-resistant prostate cancer as defined by disease progression despite castration by orchiectomy or ongoing ADT. 4. PSA at screening visit 1 ng/mL or more. 5. Provision of baseline fresh or archival tumor biopsy of prostate carcinoma is mandatory. 6. Evidence of disease progression within 6 months prior to screening with at least one of the following: 1. PSA progression defined by a minimum of 3 rising PSA levels with an interval of 1 week or more between each determination. 2. Radiographic progression of soft tissue disease by RECIST v1.1 criteria with or without PSA progression. 3. Radiographic progression of bone metastasis by PCWG3 criteria with 2 or more documented new bone lesions on a bone scan with or without PSA progression. 7. Part A: Module 1 and Module 2: 1. Part A: Module 1 and Module 2 prior anti-cancer treatment requirements as stated in study protocol 2. Pharmacodynamic backfill cohort(s) only: lesion amenable for biopsy and be willing to undergo biopsy, distinct from any target lesion used in the RECIST v1.1 evaluation, unless there are no other lesions available for biopsy. 8. Part B: Module 1 and Module 2: 1. Part B: Module 1 and Module 2 prior anti-cancer treatment requirements as stated in study protocol. 2. Participants may have received PARP inhibitors or checkpoint inhibitors per local treatment guidelines. 3. Sampling Requirements as stated in study protocol. 9. ECOG PS score of 0 or 1. 10. Adequate hematological, renal, bone marrow, and liver function as documented in the protocol. 11. Body weight 35 kg or more. 12. Male, as assigned at birth, inclusive of all gender identities. 13. Contraceptive use by participants or participant partners as documented in the protocol and consistent with local regulations.
Exclusion criteria
Exclusion criteria: 1. Any evidence of diseases (such as severe or uncontrolled systemic diseases) which in the Investigator's opinion makes it undesirable for the participant to participate in the study. 2. One or more of the following: 1. Mean resting corrected QT interval > 470 ms, 2. History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause Torsades de Pointes. 3. Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives. 4. Inadequate cardiac function of LVEF 10 mg prednisone/day or equivalent. 11. CNS pathology (examples in protocol). 12. Active or uncontrolled hepatitis B or C virus infection (exceptions listed in the protocol). 13. Known HIV infection that is not well controlled (definition for HIV infection that is well controlled is listed in protocol). 14. Radiation therapy within 4 weeks of first dose of study intervention (or local or focal radiotherapy within 2 weeks of first dose). 15. Prior anti-cancer drug exposure requirement as stated in study protocol 16. Previous anti-cancer treatment requirements as stated in study protocol 17. Systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent < 7 days prior to first dose. 18. Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose. 19. Receipt of the last dose of anti-cancer therapy or participation in another clinical study with last dose administered in the last 21 days or 5 half-lives, whichever is shorter - CAR-T cell therapy within the last 6 months prior to enrolment on this study. 20. Participants with a known hypersensitivity to AZD6621 or any of its excipients. 21. Involvement in the planning and/or conduct of the study. 22. Participant is unlikely to comply with study procedures, restrictions, and requirements (as judged by the Investigator). 23. Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention or receipt of COVID-19 vaccin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Number of participants with adverse events (AE), adverse events of special interest (AESI), and serious adverse events (SAE) [Time Frame: From time of Informed Consent to 90 days post last dose of study intervention (up to 3 years)] _Number of participants with AEs, AESIs, SAEs, including AEs leading to discontinuation of study intervention and clinically significant alterations from baseline in laboratory parameters, vital signs, ECGs and physical examination results - Number of participants with dose-limiting toxicity (DLT), as defined in the protocol (Part A only) [Time Frame: From first study dose to 21 to 28 days post first dose] _ A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness. - Preliminary anti-tumour activity of AZD6621 (PSA Response Rate) (Part B only) [Time Frame: Up to 3 years] _Number of participants with a PSA response rate | — |
Countries
Canada, China, Japan, Netherlands, South Korea, Spain, UK, USA
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed