Metastatic Prostate Cancer
Conditions
Keywords
Metastatic Castration-Resistant Prostate Cancer, Dose escalation study, Anti-cancer agents, Antibody-drug conjugate, Anti-Six-transmembrane epithelial antigen of the prostate 2 (anti-STEAP2), Metastatic castration resistant prostate cancer (mCRPC), AZD0516
Brief summary
The main purpose of this study is to assess the safety and tolerability of AZD0516 as monotherapy and/or in combination with other anti-cancer agents for treatment of metastatic prostate cancer.
Detailed description
This is a first-in-human modular, Phase I/IIa, open-label, multi-centre study of AZD0516 in participants with metastatic prostate cancer. The study will consist of individual modules, each evaluating the safety, tolerability, preliminary efficacy, PK, pharmacodynamic, and immunogenicity of AZD0516. Module 1: Evaluates AZD0516 as monotherapy. It may include 3 parts, Part A- Dose Escalation, Part B- Dose Optimisation, and Part C- Efficacy Expansion. Module 2: Evaluates AZD0516 in combination with AZD9574. It may include 2 parts, Part A - Dose Escalation and Part B Dose Optimisation.
Interventions
Sponsors
AstraZeneca
Parexel
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of metastatic adenocarcinoma of the prostate. Focal high grade neuroendocrine features are permitted. * Measurable PSA ≥ 1 μg/L (≥ 1 ng/mL). * Surgically or medically castrated with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within ≤ 28 days 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 * Life expectancy of at least 12 weeks in the opinion of the investigator * 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 ≥ 1 week between each determination. The PSA value at the screening visit should be ≥ 1 μg/L (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. Main
Exclusion criteria
* Cancer related spinal cord compression, or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of \> 10 mg prednisone/day or equivalent for at least 4 weeks prior to study enrolment. * History of leptomeningeal carcinomatosis. * Unresolved toxicities of Grade ≥ 2 (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 | Description |
|---|---|---|
| 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) | From Day 1 up to approximately 3 years | 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) | From Day 1 up to end of DLT period (approximately 21 days) | 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 | Up to approximately 2 years | The PSA50 response rate is defined as the percentage of participants achieving ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Module 1 and 2: Part A: Percentage of participants with PSA50 response rate | Up to approximately 2 years | The PSA50 response rate is defined as the percentage of participants achieving ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result. |
| Module 1 and 2: Parts A, B and C: Percentage of participants with PSA90 response rate | Up to approximately 2 years | The PSA90 response rate is defined as the percentage of participants with a confirmed ≥ 90% decrease in PSA from baseline to the lowest post-baseline PSA result. |
| Module 1 and 2: Parts A, B and C: Time to PSA 50 response (TTPSA50) | Up to approximately 2 years | The TTPSA response is defined as the time from the date of first dose of study intervention until the date of first documented PSA50 response (≥ 50% decrease in PSA from baseline, respectively) that is confirmed by a second consecutive PSA assessment at least 3 weeks later. |
| Module 1 and 2: Parts A, B and C: Time to PSA response (TTPSA90) | Up to approximately 2 years | The TTPSA response is defined as the time from the date of first dose of study intervention until the date of first documented PSA90 response (≥ 90% decrease in PSA from baseline, respectively) that is confirmed by a second consecutive PSA assessment at least 3 weeks later. |
| Module 1 and 2: Parts A, B and C: Duration of PSA response 50 (DoPSA50) | Up to approximately 2 years | The DoPSA50 is defined as the time from the date of first documented PSA50 response, that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, until the date of documented PSA progression. |
| Module 1 and 2: Parts A, B and C: Duration of PSA response 90 (DoPSA90) | Up to approximately 2 years | The DoPSA90 is defined as the time from the date of first documented PSA90 response, that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, until the date of documented PSA progression. |
| Module 1 and 2: Parts A, B and C: Percentage of participants with Durable PSA response rate 50 (DRRPSA50) | Up approximately 2 years | The DRRPSA50 is defined as the percentage of participants who have a documented PSA50 response that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, with a duration of at least 6 months. |
| Module 1 and 2: Parts A, B and C: Percentage of participants with Durable PSA response rate 90 (DRRPSA90) | Up to approximately 2 years | The DRRPSA90 is defined as the percentage of participants who have a documented PSA90 response that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, with a duration of at least 6 months. |
| Module 1 and 2: Parts A, B and C: Time to PSA Progression (TTPSA) | Up to approximately 2 years | TTPSA progression is defined as time from the date of first dose of study intervention until the date of documented PSA progression or the last PSA result in the absence of progression. |
| Module 1 and 2: Parts A, B and C: Percentage change from baseline in PSA levels | Up to approximately 2 years | The percentage change from baseline in PSA levels will be assessed. |
| Module 1 and 2: Parts A, B and C: Percentage of participants with Overall Response Rate (ORR) | Up to approximately 3 years | The ORR is defined as the percentage of participants with a confirmed tumour response of Complete Response (CR) or Partial Response (PR). |
| Module 1 and 2: Parts A, B and C: Percentage of participants with Best Overall Response (BOR) | Up to approximately 3 years | The BOR is defined as the best overall visit response achieved by participant. |
| Module 1 and 2: Parts A, B and C: Duration of Response (DoR) | Up to approximately 3 years | The DoR is defined as the time from the date of first documented objective response (which is subsequently confirmed) until the date of radiographic disease progression or censoring. |
| Module 1 and 2: Parts A, B and C: Percentage of participants with Durable Response Rate (DRR) | Up to approximately 3 years | The DRR is defined as the percentage of participants who have a confirmed response with a duration of at least 6 months. |
| Module 1 and 2: Parts A, B and C: Percentage of participants with Disease Control Rate (DCR) | Up to approximately 3 years | The DCR is defined as the percentage of participants who have a BOR of confirmed CR or PR or Stable Disease (SD). |
| Module 1 and 2: Parts A, B and C: Time to Response (TTR) | Up to approximately 3 years | The TTR is defined as the time from the date of first dose of study intervention until the date of first documented objective response, which is subsequently confirmed. |
| Module 1 and 2: Parts A, B and C: Percentage Change in Tumour Size | Up to approximately 3 years | The best percentage change from baseline in tumour size is the largest decrease (or smallest increase) from baseline for a participant, using response evaluation criteria in solid tumors (RECIST) v1.1 assessments. |
| Module 1 and 2: Parts A, B and C: Radiographic Progression-free Survival (rPFS) | Up to approximately 3 years | rPFS is defined as the time from date of first dose of study intervention until the date of objective disease progression according to RECIST v1.1 (for soft tissue disease) and prostate cancer working group 3 (PCWG3) criteria (for bone disease) as assessed by the investigator at the local site, or death (by any cause in the absence of progression). |
| Module 1 and 2: Parts A, B and C: Overall Survival (OS) | Up to approximately 3 years | OS is defined as the time from date of first dose of study intervention until death due to any cause. |
| Module 1 and 2: Part A and B: Changes in Plasma concentration of AZD0516 | From Day 1 up to approximately 3 years | To characterise the pharmacokinetics (PK) of AZD0516 when given as monotherapy and in combination with anti-cancer agents. |
| Module 1 and 2: Parts A and B: Area under concentration-time curve (AUC) | From Day 1 up to approximately 3 years | To characterise the PK (AUC) of AZD0516 when given as monotherapy and in combination with anti-cancer agents. |
| Module 1 and 2: Parts A and B: Maximum observed drug concentration (Cmax) | From Day 1 up to approximately 3 years | To characterise the PK (Cmax) of AZD0516 when given as monotherapy and in combination with anti-cancer agents. |
| Module 1 and 2: Parts A and B: Time to reach maximum observed concentration (tmax) | From Day 1 up to approximately 3 years | To characterise the PK (tmax) of AZD0516 when given as monotherapy and in combination with anti-cancer agents. |
| Module 1 and 2: Parts A and B: Tobal Body Clearance (CL) | From Day 1 up to approximately 3 years | To characterise the PK (CL) of AZD0516 when given as monotherapy and in combination with anti-cancer agents. |
| Module 1 and 2: Parts A and B: Half-life (t1/2) | From Day 1 up to approximately 3 years | To characterise the PK (t1/2) of AZD0516 when given as monotherapy and in combination with anti-cancer agents. |
| Module 1 and 2: Parts A and B: Plasma concentration of total antibody (conjugated and unconjugated) | From Day 1 up to approximately 3 years | This refers to the total amount of antibody present in a sample, regardless of whether it's attached to a drug (conjugated) or not (unconjugated). It includes a) Antibodies that are linked to the drug(conjugated antibodies) b) Antibodies that are not linked to any drug (unconjugated antibodies). This measurement gives an overall picture of the antibody concentration, which is important for understanding the pharmacokinetics of the ADC. |
| Module 1 and 2: Parts A and B: Plasma concentration of total unconjugated payload | From baseline up to approximately 3 years | The "payload" typically refers to the cytotoxic drug that is attached to the antibody in an antibody drug conjugate (ADC). "Unconjugated payload" means the drug molecules that are not attached to any antibody. "Total unconjugated payload" refers to the total amount of free drug present in the sample. This measurement is crucial for assessing the stability of the ADC and understanding how much of the drug has been released from the antibody. |
| Module 1 and 2: Parts A and B: Change from baseline in STEAP2 tumour expression | From baseline up to approximately 3 years | Target expression of STEAP2 will be evaluated using an analytically validated IHC assay. |
| Module 1 and 2: Parts A and B: Association of STEAP2 expression with AZD0516 response | From baseline up to approximately 3 years | Expression of STEAP2 will be evaluated using an analytically validated IHC assay. |
| Module 1 and 2: Parts A and B: Number of participants with positive antidrug antibodies (ADAs) | Up to approximately 3 years | To determine the immunogenicity of AZD0516 as monotherapy and in combination with anti-cancer agents. |
| Module 1: Part C: Number of participants with AEs, SAEs and AESIs | From Day 1 up to approximately 3 years | To further assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents. |
Countries
Brazil, China, France, Italy, Japan, Poland, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed