Clinical trial NCT06879041: A Phase I Study of [225Ac]-AZD2284 in Patients With Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase I, First-in-human, Dose Escalation Study Of [225Ac]-AZD2284 in Patients With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Castration-Resistant Prostate Cancer
Keywords: Dose Escalation Study
Metastatic Prostate Cancer
Radiopharmaceutical
Radiotheranostics
Castration-Resistant Prostate Cancer
Radiotherapy
Six Transmembrane Epithelial Antigen of the Prostate 2 (STEAP2)
Actinium
Radioconjugate
Radioligand
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2025-03-17
Enrollment: 134
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The main purpose of the study is to assess the safety and tolerability of AZD2284, AZD2287, and AZD2275.

Detailed description: This is a first-in-human, Phase I, non-randomized, open-label clinical trial designed to evaluate AZD2284, AZD2287, and AZD2275.

This trial will consist of 2 Parts:

Part A (Imaging):

* Part A (Cold Antibody Exploration): aims to determine the optimal dosing regimen, with or without unconjugated antibody (AZD2275) pre-administration to improve the biodistribution of AZD2287.
* Part A Expansion: aims to explore the prevalence of PSMA and STEAP2 expression by imaging.

Part B (Therapeutic):

* Part B (Actinium-225 Dose Escalation): aims to assess the safety, tolerability, and efficacy of escalating doses of AZD2284 informed by the optimal dosing regimen identified in Part A.
* Part B Expansion Cohorts 1 and 2: aims to explore efficacy of AZD2284.

Eligibility criteria: Main Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Histologically confirmed diagnosis of adenocarcinoma of the prostate or neuroendocrine differentiated prostate cancer.
* Must have had prior bilateral orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L).
* At least one metastatic lesion present on baseline Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or bone scan obtained ≤ 28 days prior to the first dose of Investigational Medicinal Product (IMP). Participants may have non-measurable lesions including bone only metastases.
* Adequate organ function

Main Exclusion Criteria:

* Treatment with any radiopharmaceutical within 6 weeks of the first dose of Investigational Medicinal Product (IMP).
* Radiation therapy (RT) within 28 days prior to the first dose and all RT-related events have not recovered to Grade ≤ 1.
* Administration of any systemic cytotoxic or investigational therapy ≤ 28 days of the first dose of IMP or 5 half-lives, whichever is shorter.
* All prior treatment-related adverse events must have resolved to Grade ≤ 1.
* Concurrent severe and/or uncontrolled illness not related to cancer and/or social situation that would limit compliance with study requirements.
* Known or suspected allergies or contraindications to any of the investigational drugs or any component of the investigational drug formulation.
* Clinically relevant proteinuria

Primary outcomes:
measure: Number of participants with adverse event (AEs)
timeFrame: Part A: From Screening (Day -28) to Day 28; Part B: Screening (Day -42 to Day -14) up to 5 years
measure: Number of participants with Dose Limiting Toxicities (DLTs)
timeFrame: Part B: Screening (Day -42 to Day -14) up to 2 cycles (84 days) of AZD2284
measure: Estimates of residence time
timeFrame: Part A: Up to Day 8 after dosing with AZD2287 on Day 1
measure: Absorbed radiation doses for AZD2287 and AZD2284
timeFrame: Part A: Up to Day 8 after dosing with AZD2287 on Day 1; Part B: Up to Day 8 after dosing with AZD2287 on Day -14
measure: Compare organ uptake of AZD2287 with and without pre-dose administration of AZD2275
timeFrame: Part A: Up to Day 8 after dosing with AZD2287 on Day 1; Part B: Up to Day 8 after dosing with AZD2287 on Day -14
measure: Tumor uptake of AZD2287 in selected regions of interest on SPECT/CT and/or planar images
timeFrame: Part A: Up to Day 8 after dosing with AZD2287 on Day 1; Part B: Up to Day 8 after dosing with AZD2287 on Day -14
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 12 months after the last dose of AZD2284
measure: Proportion of participants with Prostate-Specific Antigen (PSA) 50
timeFrame: Up to 12 months after the last dose of AZD2284
measure: Proportion of participants with PSA90
timeFrame: Up to 12 months after the last dose of AZD2284
measure: Time to maximum PSA % decline
timeFrame: Up to 12 months after the last dose of AZD2284
measure: Duration of Response (DoR)
timeFrame: Up to 12 months after the last dose of AZD2284
measure: Radiographic Progression Free Survival (rPFS)
timeFrame: Up to 12 months after the last dose of AZD2284
measure: Overall Survival (OS)
timeFrame: Part A: Up to Day 28; Part B: Up to 5 years
measure: Pharmacokinetic Clearance
timeFrame: Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days)
measure: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days)
measure: Maximum observed drug concentration (Cmax)
timeFrame: Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days)
measure: Half-life (t1/2)
timeFrame: Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days)
measure: Changes in plasma concentrations of AZD2287 and AZD2284 following AZD2275 pre-administration compared to AZD2287 and AZD2284 alone
timeFrame: Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days)
measure: Number of participants with positive antidrug antibodies (ADAs)
timeFrame: Part A dose exploration: Up to Day 28; Part B: Up to End of Trial (approximately 1 year)
Other outcomes:
Locations:
city: Miami
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: East Melbourne
country: Australia
facility: Research Site
city: CapeTown
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
Study officials:
References: