Study of AZD0754 in Participants With Metastatic Prostate Cancer

NCT06267729 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D9660C00001
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 15

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and antitumour activity of AZD0754 CAR T-cell therapy in participants with metastatic prostate cancer.

Conditions

Metastatic Prostate Cancer

Keywords

Prostate Cancer; Metastatic Prostate Cancer; mCRPC; Metastatic castration-resistant prostate cancer; CART; CAR-T; AZD0754

Outcome Measures

Primary Outcomes (1)

• Incidence of participants with Dose-limiting Toxicity (DLTs)/DLT-like events, Adverse Events (AEs), including Adverse Events of Special Interest (AESIs) and Serious Adverse Events (SAEs).

  Determine if treatment with AZD0754 is safe and tolerable through assessment of DLTs/DLT-like events, AEs, AESIs, SAEs, and changes from baseline in laboratory parameters, vital signs, and ECGs.

  Through study completion, an average of 2 years

Secondary Outcomes (22)

• Prostate-specific antigen (PSA) response rate - PSA50

  Through study completion, an average of 2 years

• PSA response rate - PSA90

  Through study completion, an average of 2 years

• Duration of PSA Response (DoPSA50, DoPSA90)

  Through study completion, an average of 2 years

• Durable PSA Response Rate (DRRPSA50, DRRPSA90)

  Through study completion, an average of 2 years

• Time to PSA Response (TTPSA50, TTPSA90)

  Through study completion, an average of 2 years

Study Arms (2)

AZD0754

EXPERIMENTAL

AZD0754 monotherapy for treatment of participants with metastatic prostate cancer.

Biological: AZD0754

AZD2287

EXPERIMENTAL

AZD2287 is a novel imaging agent for STEAP2

Biological: AZD2287

Interventions

AZD0754 BIOLOGICAL

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to produce AZD0754. During AZD0754 production, subjects may receive bridging therapy for disease control. Upon successful generation of AZD0754 product, subjects will receive treatment with AZD0754 therapy. Study treatment will include lymphodepleting chemotherapy. After lymphodepleting chemotherapy AZD0754 is administered intravenously and patients will be required to stay at the hospital for a protocol specified monitoring period.

AZD0754

AZD2287 BIOLOGICAL

This is an Optional arm of the study, which subjects will separately consent to if they would like to participate. Subjects will receive doses of a radioactive imaging agent called AZD2287 followed by SPECT/CT imaging scans at two time points.

AZD2287

Eligibility Criteria

• Age: 18 Years - 130 Years
• Gender Eligibility Details: Male Participants
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age
• Participant must be 18 years or older at the time of signing the informed consent form.
• Type of Participant and Disease Characteristics
• Participants with:
• A histologically confirmed diagnosis of metastatic adenocarcinoma of the prostate without known neuroendocrine differentiation or small cell features.
• Castration-resistant prostate cancer as defined by disease progression despite castration by orchiectomy or ongoing luteinising hormone-releasing hormone analogue. Participants receiving medical castration therapy with gonadotropin releasing hormone analogues should continue this treatment during the study.
• Measurable PSA \>/=1 ng/mL AND
• Evidence of progression within 6 months prior to screening according to one of the following:
• (i) Radiographic disease progression in soft tissue based on Response Evaluation Criteria in Solid Tumours Version 1.1 criteria with or without PSA progression as per Prostate Cancer Working Group Criteria 3 (PCWG3) (ii) Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan as per Prostate Cancer Working Group Criteria 3 (PCWG3).
• (iii) Evidence of disease progression in bone according to PSMA PET scan results in tandem with PSA progression according to PCWG3 criteria."
• Participant has previously received a NHA (ie, abiraterone, enzalutamide, apalutamide, darolutamide) and a taxane as part of their treatment for prostate cancer (whether before or in the metastatic castration-resistant setting). Participants who are ineligible for taxanes or refuse these therapies may be enrolled at the discretion of the investigator.
• For participants with pathogenic mutations in BRCA1 or BRCA2, they must also have received a PARP-inhibitor or be intolerant of this therapy. For participants with non-BRCA HRR deficiency disease, treatment with a PARP-inhibitor is at the discretion of the Investigator based on a risk/benefit analysis and discussion with the participant.
• For participants who have high microsatellite instability or deficient DNA mismatch repair they must also have received at least one line of checkpoint inhibitors (ie, pembrolizumab), not be eligible for, or be intolerant to therapy as per NCCN or local treatment guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to apheresis.
• Minimum life expectancy of \> 12 weeks prior to apheresis in the opinion of the Investigator

You may not qualify if:

• Participants with weight less than 39 kg
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease (≥ 2 years) before the first dose of study intervention and of low potential risk for recurrence. Such exceptions include non-melanoma cancer of the skin that has undergone curative therapy or adequately treated carcinoma in situ without evidence of disease.
• Participants with known brain metastases.
• Prior solid organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion:
• Participants with vitiligo or autoimmune alopecia.
• Participants with autoimmune hypothyroidism (eg, following Hashimoto thyroiditis) stable on hormone replacement.
• Any chronic inflammatory or autoimmune skin condition that does not require systemic therapy.
• Participants without active disease in the last 5 years may be included, but only after consultation with the Sponsor.
• Participants with coeliac disease controlled by diet alone.
• Stroke, intracranial haemorrhage, or seizure within 6 months of apheresis.
• Cardiac arrhythmias, (such as multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which are symptomatic or require treatment (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 3) unless controlled by pacemaker (discussion with the Study Physician required); symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia.
• Investigator judgement of one or more of the following:
• Mean resting corrected QT interval \> 470 ms, obtained from triplicate electrocardiograms (ECGs) performed at screening.
• History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and be associated with Torsades de Pointe.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (15)

Research Site

Duarte, California, 91010, United States

RECRUITING

Research Site

Tampa, Florida, 33612, United States

RECRUITING

Research Site

Atlanta, Georgia, 30322, United States

RECRUITING

Research Site

Westwood, Kansas, 66205, United States

NOT YET RECRUITING

Research Site

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Research Site

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Research Site

St Louis, Missouri, 63110, United States

RECRUITING

Research Site

Hackensack, New Jersey, 07601, United States

RECRUITING

Research Site

New York, New York, 10032, United States

RECRUITING

Research Site

New York, New York, 10065, United States

RECRUITING

Research Site

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Research Site

Dallas, Texas, 75235, United States

NOT YET RECRUITING

Research Site

Houston, Texas, 77030, United States

RECRUITING

Research Site

East Melbourne, 3002, Australia

RECRUITING

Research Site

Pamplona, 31008, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open-Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2024
• First Posted: February 20, 2024
• Study Start: March 12, 2024
• Primary Completion (Estimated): November 24, 2026
• Study Completion (Estimated): November 24, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• 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 refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• 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. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (13); ES (1); AU (1)