Metastatic Prostate Cancer
Conditions
Interventions
Experimental: Arm 1: AZD0516 monotherapy
Participants with mCRPC will receive AZD0516 monotherapy.
Experimental: Arm 2: AZD0516 + AZD9574
Participants with mCRPC will receive AZD0516 in combination wi
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically or cytologically confirmed diagnosis of metastatic adenocarcinoma of the prostate. Focal high grade neuroendocrine features are permitted. - Measurable PSA 1 mcg/L or more (1 ng/mL or more). - Surgically or medically castrated with serum testosterone levels 50 ng/dL or less (1.75 nmol/L or less) within 28 days or less before treatment allocation. Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone (GnRH) modulator for participants who have not undergone bilateral orchiectomy must be initiated at least 2 weeks prior to consent and must continue throughout the study. - Eastern cooperative oncology group (ECOG) performance status of 0 or 1. - Adequate organ and marrow function in the absence of blood transfusion or growth factor support (within 21 days prior to the scheduled first dose of study intervention). - Provision of baseline archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tumour sample is mandatory. - Documented current evidence of metastatic prostate cancer - Documented mCRPC progression at screening as assessed by the investigator with at least one of the following criteria: 1. PSA progression defined by a minimum of 3 rising PSA levels with an interval of or more 1 week between each determination. The PSA value at the screening visit should be 1 mcg/L or more (1 ng/mL). 2. Radiographic disease progression in soft tissue based on response evaluation criteria in solid tumors (RECIST) v1.1 criteria with or without PSA progression as per prostate cancer working group 3 (PCWG3). 3. Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on a bone scan as per PCWG3 with or without PSA progression.
Exclusion criteria
Exclusion criteria: - Cancer related spinal cord compression, or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of more 10 mg prednisone/day or equivalent for at least 4 weeks prior to study enrolment. - History of leptomeningeal carcinomatosis. - Unresolved toxicities of Grade 2 or more (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from prior therapy (excluding vitiligo, alopecia, and endocrine disorders that are controlled with replacement hormone therapy). - Uncontrolled intercurrent illness within the last 12 months. - Cardiovascular disorder (History of arrhythmia, uncontrolled hypertension, symptomatic hypotension, history of brain perfusion problems, symptomatic heart failure, prior or current cardiomyopathy, severe valvular heart disease) - History of malignancy - History of non-infectious interstitial lung disease (ILD)/pneumonitis - Active infection exclusions, including tuberculosis and infections with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV). - Any known predisposition to bleeding - Clinically severe pulmonary compromise - Participants with Myelodysplastic syndrome (MDS)/Acute Myeloid Leukemia (AML) or with features suggestive of MDS/AML. - Previous treatment with a STEAP2 targeting modality, chemotherapeutic agent that inhibits topoisomerase activity or metabolic enzymes.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Module 1 and 2: Parts A and B: Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interests (AESIs) Part A: To assess the safety and tolerability and to determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) of AZD0516 as monotherapy and in combination with anti-cancer agents. Part B: To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents. - Module 1 and 2: Part A: Number of participants with Dose Limiting Toxicities (DLTs) To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents. - Module 1: Parts B and C and Module 2: Part B: Percentage of participants with Prostate-Specific Antigen (PSA) 50 response rate The PSA50 response rate is defined as the percentage of participants achieving 50% or more decrease in PSA from baseline to the lowest post-baseline PSA result. | — |
Countries
Brazil, China, France, Italy, Japan, Poland, South Korea, Spain, United Kingdom, United States
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed