A Phase I/II Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD6621, a T Cell-engaging Antibody That Targets STEAP2, CD3, and CD8 in Adult Participants With Metastatic Prostate Cancer
This study is being conducted to learn more about the safety, tolerability, and effectiveness of an experimental treatment for metastatic prostate cancer called AZD6621. The study is split into different modules which will look at AZD6621 delivered by different methods. The study is also further split into 2 parts, Part A which will test different dose levels of AZD6621 to determine which doses are the best in terms of safety and side effects (dose escalation), and Part B will further test at least two AZD6621 doses in a larger group of participants (dose expansion).
• Capable of giving signed informed consent and complying to the study protocol.
• Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form.
• ≥ 18 years of age at the time of signing the informed consent form.
• Participants with:
∙ Histologically confirmed diagnosis of metastatic adenocarcinoma of the prostate
‣ Surgically or medically castrated, with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) ≤ 28 days 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.
‣ Castration-resistant prostate cancer as defined by disease progression despite castration by orchiectomy or ongoing ADT.
‣ PSA at screening visit ≥ 1 ng/mL.
• Provision of baseline fresh or archival tumor biopsy of prostate carcinoma is mandatory.
• Evidence of disease progression within 6 months prior to screening with at least one of the following:
∙ PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination.
‣ Radiographic progression of soft tissue disease by RECIST v1.1 criteria with or without PSA progression.
‣ 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.
• Part A: Module 1 and Module 2:
∙ Part A: Module 1 and Module 2 prior anti-cancer treatment requirements as stated in study protocol
‣ 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.
• Part B: Module 1 and Module 2:
∙ Part B: Module 1 and Module 2 prior anti-cancer treatment requirements as stated in study protocol.
‣ Participants may have received PARP inhibitors or checkpoint inhibitors per local treatment guidelines.
‣ Sampling Requirements as stated in study protocol.
• ECOG PS score of 0 or 1.
⁃ Minimum life expectancy of \> 12 weeks.
⁃ Adequate hematological, renal, bone marrow, and liver function as documented in the protocol.
⁃ Body weight ≥ 35 kg.
⁃ Male, as assigned at birth, inclusive of all gender identities.
⁃ Contraceptive use by participants or participant partners as documented in the protocol and consistent with local regulations.