Metastatic Prostate Cancer
Conditions
Keywords
Prostate, STEAP2, T Cell-engaging Antibody, CD8
Brief summary
This study is being conducted to learn more about the safety, tolerability, and effectiveness of an experimental treatment for metastatic prostate cancer called AZD8359. The study is split into different modules which will look at AZD8359 delivered by different methods. The study is also further split into 2 parts, Part A which will test different dose levels and dosing schedules of AZD8359 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 AZD8359 doses in a larger group of participants (dose expansion).
Detailed description
This is a first-in-human, modular, Phase I/II, open label, multicenter study of AZD8359, in adult participants with metastatic prostate cancer. The study will consist of study modules, each evaluating the the safety, tolerability, preliminary efficacy, immune cell activation and anti-tumor activity of AZD8359. The study will also characterize the pharmacokinetics and immunogenicity of AZD8359.
Interventions
DRUGAZD8359
AZD8359 Monotherapy Administration route 1
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a first in human, multicenter, open-label, dose-escalation and dose-expansion study. The study includes 2 Modules; Module 1 is investigating AZD8359 given on its own by one method of administration, and Module 2 is investigating AZD8359 on its own by a different method of administration. The study also has 2 parts: Part A Dose Escalation and Part B Dose Expansion. Part B Dose expansion will assess at least 2 doses or dosing schedules in either module. Participants will be randomised in Part B to one of these cohorts whenever possible
Eligibility
Sex/Gender
MALE
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of adenocarcinoma of the prostate or neuroendocrine differentiated prostate cancer * Surgically or medically castrated with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) * PSA value at screening should be ≥ 1ng/mL * Evidence of disease progression within 6 months prior to screening * Part A Participants should have received at least 2 prior approved systemic therapies for prostate cancer with at least one androgen receptor pathway inhibitor and at least one taxane regimen if amenable * Part B Participants should have received an androgen receptor pathway inhibitor for metastatic hormone sensitive prostate cancer or metastatic castration resistant prostate cancer (mCRPC). No prior taxane treatment for mCRPC is allowed for Module 1 and 2 Part B patients * Adequate organ function * Body weight ≥ 35 kg
Exclusion criteria
* Any clinically relevant cardiac abnormalities such as QT prolongation or uncontrolled cardiac arrythmias * All prior treatment-related adverse events must have resolved to Grade ≤ 2 * History of Grade ≥ 3 cytokine release syndrome or Grade ≥ 2 immune effector cell-associated neurotoxicity syndrome with prior therapy * Active or prior documented autoimmune or inflammatory disorders within the past 3 years * Prior exposure to any STEAP2 targeted agents or TCEs for prostate cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA response rate (Part B only) | Up to 3 years | Number of participants with a PSA50 response |
| Number of participants with adverse events (AE), adverse events of special interest (AESI), and serious adverse events (SAE) | 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) | From first study dose to 21 OR 28 days post first dose based on schedule | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Durable Response Rate (DRR) | Up to 3 years | Percentage of participants who have a confirmed best overall response of Complete Response or Partial Response with a duration at specific milestones (e.g., 3 months, 6 months, 12 months) |
| Target Lesion Percentage change | Up to 3 years | Percentage change in Target Lesion size according to RECIST v1.1. |
| Overall Survival (OS) 12 months | 12 months | Overall Survival at 12 months |
| Overall Survival (OS) | Up to 3 years | Median Overall Survival |
| Symptomatic Skeletal Related Events (SSRE) | Up to 3 years | Time to first symptomatic skeletal-related events (SSRE) |
| Serum Concentration of AZD8359 | From first dose through Day 28 after the last study-drug dose, at predefined intervals | Serum concentrations of the study drug |
| Pharmacokinetics of AZD8359 (Cmax) | From first dose through Day 28 after the last study-drug dose, at predefined intervals | Maximum observed plasma concentration of the study drug (Cmax). |
| Pharmacokinetics of AZD8359 (AUC) | From first dose through Day 28 after the last study-drug dose, at predefined intervals | Area under the plasma concentration-time curve (AUC) |
| Pharmacokinetics of AZD8359 (Tmax) | From first dose through Day 28 after the last study-drug dose, at predefined intervals | The time it takes for study drug to reach the maximum concentration (Tmax) |
| Pharmacokinetics of AZD8359 (Clerance) | From first dose through Day 28 after the last study-drug dose, at predefined intervals | The volume of plasma completely cleared of a study drug per unit of time |
| Pharmacokinetics of AZD8359 (t1/2) | From first dose through Day 28 after the last study-drug dose, at predefined intervals | Terminal elimination half life of study drug (t1/2) |
| Immunogenicity of AZD8359 (ADA) | From first dose through Day 28 after the last study-drug dose, at predefined intervals | The number and percentage of participants who develop detectable anti-drug antibodies (ADA) |
| Tumor STEAP2 expression | Up to 3 years | STEAP2 expression in tumor as measured by immunohistochemistry (IHC) |
| PSA Response rate (Part A only) | Up to 3 years | Number of participants with a PSA50 response |
| PSA Response rate | Up to 3 years | Number of participants with a PSA90 response |
| Time to PSA response | Up to 3 years | Time taken to achieve a PSA response |
| Duration of PSA response | Up to 3 years | Time PSA response lasts |
| Durable PSA response rate | Up to 3 years | Percentage of participants who have a confirmed PSA response with a duration of at least 6 months |
| Time to PSA progression | Up to 3 years | Time to achieve PSA progression after a PSA response |
| Objective Response Rate (ORR) | Up to 3 years | Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 for soft tissue disease and PCWG3 for bone disease |
| Disease Control Rate (DCR) | 16 Weeks | Percentage of participants who have a Best Overall Response (BOR) of confirmed Complete Response (CR), Partial Response (PR) or Stable Disease (SD) according to RECIST v1.1 for soft tissue disease and PCWG3 for bone disease |
| Duration of Response (DoR) | Up to 3 years | Time from the date of first Objective Response (OR) until date disease progression or death in the absence of disease progression according to RECIST v1.1 for soft tissue disease and PCWG3 for bone disease |
| Time To Response (TTR) | Up to 3 years | Time from study drug administration date until the date of first Objective Response (OR) according to RECIST v1.1 for soft tissue disease and PCWG3 for bone disease |
| Radiographic Progression Free Survival (rPFS) | Up to 3 years | The time from the start of study treatment (Part A) or date of randomization (Part B) until disease progression or death in the absence of disease progression according to RECIST 1.1 for soft tissue disease and PCWG3 for bone disease |
Countries
Australia, South Korea, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed