Metastatic Castration-Resistant Prostate CancerPhase 1NCT06879041
A Phase I Study of [225Ac]-AZD2284 in Patients With Metastatic Castration-Resistant Prostate Cancer
A Phase 1 study testing AZD2287, AZD2275 and AZD2284 in people with Metastatic Castration-Resistant Prostate Cancer, run by AstraZeneca at 16 sites in 3 countries.
Trial summary
The main purpose of the study is to assess the safety and tolerability of AZD2284, AZD2287, and AZD2275. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-Resistant Prostate Cancer
- What is being tested?
- AZD2287, AZD2275 and AZD2284
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 16 sitesin 3 countries
- Study dates
- 10 Mar 2025to 16 Apr 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- eria:
- • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- • Histologically confirmed diagnosis of adenocarcinoma of the prostate without strong clinical suspicion of majority neuroendocrine differentiation.
- • 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
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- • Part A only: Metastatic prostate cancer considered to be stable or progressing metastatic castration resistant prostate cancer (mCRPC).
- • Part B only: Progressing mCRPC defined as meeting at least one of following documented criteria -
- a)Serum/plasma PSA progression
- b)Soft-tissue progression
- c)Progression of bone disease
- • Part B Dose Escalation: Previously treated with at least 2 prior lines of systemic anti-cancer therapy for mCRPC. Prior lines must include:
- a)At least 1 androgen receptor pathway inhibitor (ARPI)
- b)A poly (adp-ribose) polymerase (PARP) inhibitor for participants with known BRCA mutation
- c)A checkpoint inhibitor for participants with known microsatellite instability-high (MSI-H), deficient mismatch pair (dMMR), or tumor mutational burden (TMB) ≥ 10 mut/Mb
- • Part B Dose Expansion: Previously treated with at least 1 prior line of systemic anti-cancer therapy for mCRPC. Prior lines must include:
- (a)At least 1 ARPI
- (b)A PARP inhibitor for participants with known BRCA mutation per local practice, unless ineligible per Investigator decision.
- (c)A checkpoint inhibitor for participants with known MSI-H, dMMR, or TMB ≥ 10 mut/Mb.
- (d)No previous cytotoxic chemotherapy for CRPC. Taxanes for metastatic hormone sensitive prostate cancer (mHSPC) is acceptable if the last cycle Day 1 was > 12 months before first study treatment.
- (e)Previous treatment with prostate specific membrane antigen radioligand therapy (PSMA-RLT) or Radium-223 is allowed but not required. Participants who have had prior radiation therapy, including therapeutic radiopharmaceuticals, external bean radiation therapy (EBRT), and/or brachytherapy are eligible, subject to satisfying all other inclusion/exclusion criteria. Therapeutic radiopharmaceuticals will be considered a prior line of systemic therapy.
- Main
Who cannot join
- • Treatment with any radiopharmaceutical within 6 weeks of the first dose of Investigational Medicinal Product (IMP).
- • Radiation therapy (RT) or external beam radiation therapy (EBRT) 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.
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- • Clinically relevant proteinuria
- • Diffuse and intense osseous radiotracer uptake on bone scintigraphy or PSMA imaging characteristic of a superscan.
- • Chronic corticosteroid use greater than 10 mg prednisone equivalent daily.
Trial locations and contacts
16 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
16 sites in 3 countries
United States12 sites, 12 recruiting
- Recruiting
Research Site
Boston, Massachusetts, 02215
- Recruiting
Research Site
Chicago, Illinois, 60637
- Not yet recruiting
Research Site
Cleveland, Ohio, 44195
- Not yet recruiting
Research Site
Metairie, Louisiana, 70006
- Recruiting
Research Site
Miami, Florida, 33165
- Not yet recruiting
Research Site
New York, New York, 10032
- Recruiting
Research Site
Omaha, Nebraska, 68130
- Not yet recruiting
Research Site
Palo Alto, California, 94304
- Not yet recruiting
Research Site
Portland, Oregon, 97239
- Not yet recruiting
Research Site
Rochester, Minnesota, 55902
- Not yet recruiting
Research Site
San Diego, California, 92103
- Recruiting
Research Site
Tampa, Florida, 33612
South Africa3 sites, 2 recruiting
- Not yet recruiting
Research Site
CapeTown, 7925
- Withdrawn
Research Site
Durban, 4013
- Recruiting
Research Site
Pretoria, 181
About this study
Official title: A Phase I, First-in-human, Dose Escalation Study Of [225Ac]-AZD2284 in Patients With Metastatic Castration-Resistant Prostate Cancer
The main purpose of the study is to assess the safety and tolerability of AZD2284, AZD2287, and AZD2275.
Read the 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 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.
- Being tested
- AZD2287, AZD2275, AZD2284
- 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
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD2287Drug
Participants will receive AZD2287
AZD2275Drug
Participants will receive AZD2275
AZD2284Drug
Participants will receive AZD2284
| Study group | Role | What they receive |
|---|---|---|
| Part A: Cohort A1: AZD2287 (Hot only) | Experimental | Participants will receive AZD2287. If eligible for treatment, will receive dose level (DL)1 of AZD2284. Receives: Drug: AZD2287; Drug: AZD2284 |
| Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot) | Experimental | Participants will receive DL1 of AZD2275 followed by AZD2287. If eligible for treatment, will receive DL1 of AZD2284. Receives: Drug: AZD2287; Drug: AZD2275; Drug: AZD2284 |
| Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot) | Experimental | Participants will receive DL2 of AZD2275 followed by AZD2287. If eligible for treatment, will receive DL1 of AZD2284. Receives: Drug: AZD2287; Drug: AZD2275; Drug: AZD2284 |
| Part B (Actinium-225 Dose Escalation): DL1: AZD2284 | Experimental | Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive DL1 of AZD2284. Receives: Drug: AZD2287; Drug: AZD2275; Drug: AZD2284 |
| Part B (Actinium-225 Dose Escalation): DL2: AZD2284 | Experimental | Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive DL2 of AZD2284. Receives: Drug: AZD2287; Drug: AZD2275; Drug: AZD2284 |
| Part B (Actinium-225 Dose Escalation): DL3: AZD2284 | Experimental | Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive DL3 of AZD2284. Receives: Drug: AZD2287; Drug: AZD2275; Drug: AZD2284 |
| Part B (Actinium-225 Dose Escalation): DL4: AZD2284 | Experimental | Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive DL4 of AZD2284. Receives: Drug: AZD2287; Drug: AZD2275; Drug: AZD2284 |
| Part B: Cohort E1 | Experimental | 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. Receives: Drug: AZD2287; Drug: AZD2275; Drug: AZD2284 |
| Part B: Cohort E2 | Experimental | 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. Receives: Drug: AZD2287; Drug: AZD2275; Drug: AZD2284 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse event (AEs)
Measured: Part A: Up to Day 28; Part B: Up to 5 years
Number of participants with Dose Limiting Toxicities (DLTs)
Measured: Part B: Up to 84 days of receiving AZD2284
Estimates of residence time
Measured: Part A: Up to 8 days after a dose of AZD2287
Absorbed radiation doses for AZD2287 and AZD2284
Measured: Part A: Up to 8 days after a dose of AZD2287; Part B: Up to 7 days after a dose of AZD2287
Compare organ uptake of AZD2287 with and without pre-dose administration of AZD2275
Measured: Part A: Up to 8 days after a dose of AZD2287; Part B: Up to 7 days after a dose of AZD2287
Tumor uptake of AZD2287 in selected regions of interest on SPECT/CT and/or planar images
Measured: Part A: Up to 8 days after a dose of AZD2287; Part B: Up to 7 days after a dose of AZD2287
Secondary outcomes (13)
Overall Response Rate (ORR)
Measured: Up to 12 months after the last dose of AZD2284
Proportion of participants with Prostate-Specific Antigen (PSA) 50
Measured: Up to 12 months after the last dose of AZD2284
Proportion of participants with PSA90
Measured: Up to 12 months after the last dose of AZD2284
Time to PSA50 response
Measured: Up to 12 months after the last dose of AZD2284
Duration of Response (DoR)
Measured: Up to 12 months after the last dose of AZD2284
Radiographic Progression Free Survival (rPFS)
Measured: Up to 12 months after the last dose of AZD2284
Overall Survival (OS)
Measured: Part A: Up to Day 28; Part B: Up to 5 years
Pharmacokinetic Clearance
Measured: Part A: Up to Day 28; Part B: Up to 84 days
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
Measured: Part A: Up to Day 28; Part B: Up to 84 days
Maximum observed drug concentration (Cmax)
Measured: Part A: Up to Day 28; Part B: Up to 84 days
Half-life (t1/2)
Measured: Part A: Up to Day 28; Part B: Up to 84 days
Changes in plasma concentrations of AZD2287 and AZD2284 following AZD2275 pre-administration compared to AZD2287 and AZD2284 alone
Measured: Part A: Up to Day 28; Part B: Up to 84 days
Number of participants with positive antidrug antibodies (ADAs)
Measured: Part A: Up to Day 28; Part B: Approximately 28 days after End of Treatment (EOT) visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2025
- Study start10 Mar 2025
- Primary completion16 Apr 2029 (estimated)
- Study completion16 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration-Resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 136 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06879041
- Sponsor's protocol ID
- D7580C00001
- Status last verified
- Oct 2026
- First submitted
- 11 Mar 2025
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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",indicatesthat AZ are accepting requests for IPD, but this does not mean all requests will be approved.