First-in-Human Study to Evaluate AZD8359 STEAP2 TCE in Participants With Prostate Cancer

Phase 2RecruitingNCT07529717

AstraZeneca42 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic Prostate Cancer

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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

Locations (8)

Research Site

Orlando, Florida, United States

RECRUITING

Research Site

East Brunswick, New Jersey, United States

RECRUITING

Research Site

Hackensack, New Jersey, United States

NOT_YET_RECRUITING

Research Site

Providence, Rhode Island, United States

RECRUITING

Research Site

Darlinghurst, Australia

RECRUITING

Research Site

Melbourne, Australia

RECRUITING

Research Site

Seoul, South Korea

RECRUITING

Research Site

Seoul, South Korea

RECRUITING

Outcomes

Primary Outcomes

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 Outcomes

PSA Response rate (Part A only)

Number of participants with a PSA50 response

Time frame: Up to 3 years

PSA Response rate

Number of participants with a PSA90 response

Time frame: Up to 3 years

Time to PSA response

Time taken to achieve a PSA response

Time frame: Up to 3 years

Duration of PSA response

Time PSA response lasts

Time frame: Up to 3 years

Durable PSA response rate

Percentage of participants who have a confirmed PSA response with a duration of at least 6 months

Time frame: Up to 3 years

Time to PSA progression

Time to achieve PSA progression after a PSA response

Time frame: Up to 3 years

Objective Response Rate (ORR)

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

Time frame: Up to 3 years

Duration of Response (DoR)

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 frame: Up to 3 years

Disease Control Rate (DCR)

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

Time frame: 16 Weeks

Time To Response (TTR)

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

Time frame: Up to 3 years

Radiographic Progression Free Survival (rPFS)

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

Time frame: Up to 3 years

Durable Response Rate (DRR)

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)

Time frame: Up to 3 years

Target Lesion Percentage change

Percentage change in Target Lesion size according to RECIST v1.1.

Time frame: Up to 3 years

Overall Survival (OS) 12 months

Overall Survival at 12 months

Time frame: 12 months

Overall Survival (OS)

Median Overall Survival

Time frame: Up to 3 years

Symptomatic Skeletal Related Events (SSRE)

Time to first symptomatic skeletal-related events (SSRE)

Time frame: Up to 3 years

Serum Concentration of AZD8359

Serum concentrations of the study drug