A Phase I Study of [225Ac]-AZD2284 in Patients With Metastatic Castration-Resistant Prostate Cancer
Phase 1
Recruiting
- Conditions
- Metastatic Castration-Resistant Prostate Cancer
- Interventions
- Drug: AZD2287Drug: AZD2284Drug: AZD2275
- Registration Number
- NCT06879041
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 134
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Cohort A1: AZD2287 (Hot only) AZD2287 Participants will receive 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. Part A: Cohort A1: AZD2287 (Hot only) AZD2284 Participants will receive 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot) AZD2287 Participants will receive low dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot) AZD2275 Participants will receive low dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot) AZD2284 Participants will receive low dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot) AZD2287 Participants will receive medium dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot) AZD2275 Participants will receive medium dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot) AZD2284 Participants will receive medium dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. Part A Expansion: AZD2287 + AZD2275 (Cold + Hot) AZD2287 Participants will receive dose of AZD2275 determined earlier in the study followed by 1 dose of AZD2287. Part A Expansion: AZD2287 + AZD2275 (Cold + Hot) AZD2275 Participants will receive dose of AZD2275 determined earlier in the study followed by 1 dose of AZD2287. Part B (Actinium-225 Dose Escalation): low dose: AZD2284 AZD2287 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive low dose of AZD2284. Part B (Actinium-225 Dose Escalation): low dose: AZD2284 AZD2275 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive low dose of AZD2284. Part B (Actinium-225 Dose Escalation): low dose: AZD2284 AZD2284 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive low dose of AZD2284. Part B (Actinium-225 Dose Escalation): medium dose: AZD2284 AZD2287 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive medium dose of AZD2284. Part B (Actinium-225 Dose Escalation): medium dose: AZD2284 AZD2275 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive medium dose of AZD2284. Part B (Actinium-225 Dose Escalation): medium dose: AZD2284 AZD2284 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive medium dose of AZD2284. Part B (Actinium-225 Dose Escalation): high dose 1: AZD2284 AZD2287 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284. Part B (Actinium-225 Dose Escalation): high dose 1: AZD2284 AZD2275 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284. Part B (Actinium-225 Dose Escalation): high dose 1: AZD2284 AZD2284 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284. Part B (Actinium-225 Dose Escalation): high dose 2: AZD2284 AZD2287 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284. Part B (Actinium-225 Dose Escalation): high dose 2: AZD2284 AZD2275 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284. Part B (Actinium-225 Dose Escalation): high dose 2: AZD2284 AZD2284 Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284. Part B: Cohort E1 AZD2287 Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level. Part B: Cohort E1 AZD2275 Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level. Part B: Cohort E1 AZD2284 Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level. Part B: Cohort E2 AZD2287 Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level. Part B: Cohort E2 AZD2275 Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level. Part B: Cohort E2 AZD2284 Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level.
- Primary Outcome Measures
Name Time Method Number of participants with adverse event (AEs) Part A: From Screening (Day -28) to Day 28; Part B: Screening (Day -42 to Day -14) up to 5 years Number of participants with Dose Limiting Toxicities (DLTs) Part B: Screening (Day -42 to Day -14) up to 2 cycles (84 days) of AZD2284 Estimates of residence time Part A: Up to Day 8 after dosing with AZD2287 on Day 1 Absorbed radiation doses for AZD2287 and AZD2284 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 Compare organ uptake of AZD2287 with and without pre-dose administration of AZD2275 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 Tumor uptake of AZD2287 in selected regions of interest on SPECT/CT and/or planar images 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 Outcome Measures
Name Time Method Overall Response Rate (ORR) Up to 12 months after the last dose of AZD2284 Proportion of participants with Prostate-Specific Antigen (PSA) 50 Up to 12 months after the last dose of AZD2284 Proportion of participants with PSA90 Up to 12 months after the last dose of AZD2284 Time to maximum PSA % decline Up to 12 months after the last dose of AZD2284 Duration of Response (DoR) Up to 12 months after the last dose of AZD2284 Radiographic Progression Free Survival (rPFS) Up to 12 months after the last dose of AZD2284 Overall Survival (OS) Part A: Up to Day 28; Part B: Up to 5 years Pharmacokinetic Clearance Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days) Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days) Maximum observed drug concentration (Cmax) Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days) Half-life (t1/2) Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days) Changes in plasma concentrations of AZD2287 and AZD2284 following AZD2275 pre-administration compared to AZD2287 and AZD2284 alone Part A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days) Number of participants with positive antidrug antibodies (ADAs) Part A dose exploration: Up to Day 28; Part B: Up to End of Trial (approximately 1 year)
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Molecular mechanisms of [225Ac]-AZD2284 targeting PSMA/STEAP2 in metastatic castration-resistant prostate cancer
Comparative efficacy of [225Ac]-AZD2284 vs enzalutamide/abiraterone in mCRPC patients: AstraZeneca Phase I trial
Biomarkers for PSMA/STEAP2 expression in mCRPC patient selection and [225Ac]-AZD2284 response prediction
Adverse events and safety management of [225Ac]-AZD2284 in AstraZeneca's NCT06879041 Phase I mCRPC study
AZD2275 pre-administration impact on [225Ac]-AZD2284 biodistribution in mCRPC: AstraZeneca's combination strategy
Trial Locations
- Locations (1)
Research Site
🇿🇦Pretoria, South Africa