Phase I/II Dose Escalation & Dose Optimization Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD8359, a CD8-guided T Cell-engaging Antibody That Targets STEAP2, in Adult Participants With Prostate Cancer
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.
Arms & interventions
- DrugAZD8359
AZD8359 Monotherapy Administration route 1
- DrugAZD8359
AZD8359 Monotherapy Administration route 2
- DrugAZD8359
AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 1 (RDE1)
- DrugAZD8359
AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 2 (RDE2)
Outcome measures
Primary
Number of participants with adverse events (AE), adverse events of special interest (AESI), and serious adverse events (SAE)
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
Time frame: From time of Informed Consent to 90 days post last dose of study intervention (up to 3 years)
Number of participants with dose-limiting toxicity (DLT), as defined in the protocol (Part A only)
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
Time frame: From first study dose to 21 OR 28 days post first dose based on schedule
PSA response rate (Part B only)
Number of participants with a PSA50 response
Time frame: Up to 3 years
Secondary
PSA Response rate (Part A only)
Time frame: Up to 3 years
PSA Response rate
Time frame: Up to 3 years
Time to PSA response
Time frame: Up to 3 years
Duration of PSA response
Time frame: Up to 3 years
Durable PSA response rate
Time frame: Up to 3 years
Time to PSA progression
Time frame: Up to 3 years
Objective Response Rate (ORR)
Time frame: Up to 3 years
Duration of Response (DoR)
Time frame: Up to 3 years
Disease Control Rate (DCR)
Time frame: 16 Weeks
Time To Response (TTR)
Time frame: Up to 3 years
Radiographic Progression Free Survival (rPFS)
Time frame: Up to 3 years
Durable Response Rate (DRR)
Time frame: Up to 3 years
Target Lesion Percentage change
Time frame: Up to 3 years
Overall Survival (OS) 12 months
Time frame: 12 months
Overall Survival (OS)
Time frame: Up to 3 years
Symptomatic Skeletal Related Events (SSRE)
Time frame: Up to 3 years
Serum Concentration of AZD8359
Time frame: From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (Cmax)
Time frame: From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (AUC)
Time frame: From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (Tmax)
Time frame: From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (Clerance)
Time frame: From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (t1/2)
Time frame: From first dose through Day 28 after the last study-drug dose, at predefined intervals
Immunogenicity of AZD8359 (ADA)
Time frame: From first dose through Day 28 after the last study-drug dose, at predefined intervals
Tumor STEAP2 expression
Time frame: Up to 3 years
Eligibility criteria
Study locations (4)
Research Site
Orlando, Florida, 32806
Research Site
East Brunswick, New Jersey, 08816
Research Site
Hackensack, New Jersey, 07601
Research Site
Providence, Rhode Island, 02903