First-in-Human Study to Evaluate AZD8359 STEAP2 TCE in Participants With Prostate Cancer (CRIUS-1)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Prostate Cancer
• Intervention / Treatment: Drug: AZD8359; Drug: AZD8359; Drug: AZD8359; Drug: AZD8359

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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Darlinghurst, Australia, 2010
    • Not yet recruiting
    • Research Site
  • Melbourne, Australia, 3000
    • Recruiting
    • Research Site
• South Korea
  • Seoul, South Korea, 06351
    • Recruiting
    • Research Site
  • Seoul, South Korea, 03722
    • Not yet recruiting
    • Research Site
• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Research Site
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Not yet recruiting
      • Research Site
    • Hackensack, New Jersey, United States, 07601
      • Not yet recruiting
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1 - Part A (Dose Escalation)	Drug: AZD8359; AZD8359 Monotherapy Administration route 1; Drug: AZD8359; AZD8359 Monotherapy Administration route 2; Drug: AZD8359; AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 1 (RDE1); Drug: AZD8359; AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 2 (RDE2)
Experimental: Module 2 - Part A (Dose Escalation)	Drug: AZD8359; AZD8359 Monotherapy Administration route 1; Drug: AZD8359; AZD8359 Monotherapy Administration route 2; Drug: AZD8359; AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 1 (RDE1); Drug: AZD8359; AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 2 (RDE2)
Experimental: Module 1/2 - Part B1 (Dose Expansion)	Drug: AZD8359; AZD8359 Monotherapy Administration route 1; Drug: AZD8359; AZD8359 Monotherapy Administration route 2; Drug: AZD8359; AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 1 (RDE1); Drug: AZD8359; AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 2 (RDE2)
Experimental: Module 1/2 - Part B2 (Dose Expansion)	Drug: AZD8359; AZD8359 Monotherapy Administration route 1; Drug: AZD8359; AZD8359 Monotherapy Administration route 2; Drug: AZD8359; AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 1 (RDE1); Drug: AZD8359; AZD8359 Monotherapy Administration route 1 (Module 1) or administration route 2 (Module 2) at Recommended Dose for Expansion 2 (RDE2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA Response rate (Part A only)	Number of participants with a PSA50 response	Up to 3 years
PSA Response rate	Number of participants with a PSA90 response	Up to 3 years
Time to PSA response	Time taken to achieve a PSA response	Up to 3 years
Duration of PSA response	Time PSA response lasts	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	Up to 3 years
Time to PSA progression	Time to achieve PSA progression after a PSA response	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	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	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	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	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	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)	Up to 3 years
Target Lesion Percentage change	Percentage change in Target Lesion size according to RECIST v1.1.	Up to 3 years
Overall Survival (OS) 12 months	Overall Survival at 12 months	12 months
Overall Survival (OS)	Median Overall Survival	Up to 3 years
Symptomatic Skeletal Related Events (SSRE)	Time to first symptomatic skeletal-related events (SSRE)	Up to 3 years
Serum Concentration of AZD8359	Serum concentrations of the study drug	From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (Cmax)	Maximum observed plasma concentration of the study drug (Cmax).	From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (AUC)	Area under the plasma concentration-time curve (AUC)	From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (Tmax)	The time it takes for study drug to reach the maximum concentration (Tmax)	From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (Clerance)	The volume of plasma completely cleared of a study drug per unit of time	From first dose through Day 28 after the last study-drug dose, at predefined intervals
Pharmacokinetics of AZD8359 (t1/2)	Terminal elimination half life of study drug (t1/2)	From first dose through Day 28 after the last study-drug dose, at predefined intervals
Immunogenicity of AZD8359 (ADA)	The number and percentage of participants who develop detectable anti-drug antibodies (ADA)	From first dose through Day 28 after the last study-drug dose, at predefined intervals
Tumor STEAP2 expression	STEAP2 expression in tumor as measured by immunohistochemistry (IHC)	Up to 3 years

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2026
• Primary Completion (Estimated): November 17, 2027
• Study Completion (Estimated): November 17, 2027

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: CD8; Prostate; T Cell-engaging Antibody; STEAP2
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: D8040C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from

AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No