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A Phase I Study of [225Ac]-AZD2284 in Patients With Metastatic Castration-Resistant Prostate Cancer

PHASE1RECRUITING

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

Study details:

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

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  2. Histologically confirmed diagnosis of adenocarcinoma of the prostate or neuroendocrine differentiated prostate cancer.
  3. 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).
  4. 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.
  5. Adequate organ function

Exclusion criteria

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

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1

trial

Study ID

NCT06879041

Intervention or treatment

DRUG: AZD2287

DRUG: AZD2275

DRUG: AZD2284

Conditions

  • Metastatic Castration-Resistant Prostate Cancer

  • Condition: Metastatic Castration-Resistant Prostate Cancer

  • DRUG: AZD2287 and other drugs

  • East Melbourne, Australia

  • Sponsor: AstraZeneca

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Research sites nearby

Closest Location:

Research Site

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  • Research Site

    East Melbourne, Australia

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Who is running the clinical trial?

A

AstraZeneca

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Part A: Cohort A1: AZD2287 (Hot only)
  • Participants will receive AZD2287. If eligible for treatment, will receive dose level (DL)1 of AZD2284.
Drug: AZD2287, Drug: AZD2284
    EXPERIMENTAL: Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot)
    • Participants will receive DL1 of AZD2275 followed by AZD2287. If eligible for treatment, will receive DL1 of AZD2284.
    Drug: AZD2287, Drug: AZD2275, Drug: AZD2284
      EXPERIMENTAL: Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot)
      • Participants will receive DL2 of AZD2275 followed by AZD2287. If eligible for treatment, will receive DL1 of AZD2284.
      Drug: AZD2287, Drug: AZD2275, Drug: AZD2284
        EXPERIMENTAL: Part B (Actinium-225 Dose Escalation): DL1: AZD2284
        • Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive DL1 of AZD2284.
        Drug: AZD2287, Drug: AZD2275, Drug: AZD2284
          EXPERIMENTAL: Part B (Actinium-225 Dose Escalation): DL2: AZD2284
          • Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive DL2 of AZD2284.
          Drug: AZD2287, Drug: AZD2275, Drug: AZD2284
            EXPERIMENTAL: Part B (Actinium-225 Dose Escalation): DL3: AZD2284
            • Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive DL3 of AZD2284.
            Drug: AZD2287, Drug: AZD2275, Drug: AZD2284
              EXPERIMENTAL: Part B (Actinium-225 Dose Escalation): DL4: AZD2284
              • Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive DL4 of AZD2284.
              Drug: AZD2287, Drug: AZD2275, Drug: AZD2284
                EXPERIMENTAL: Part B: Cohort E1
                • 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.
                Drug: AZD2287, Drug: AZD2275, Drug: AZD2284
                  EXPERIMENTAL: Part B: Cohort E2
                  • 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.
                  Drug: AZD2287, Drug: AZD2275, Drug: AZD2284

                    What is the study measuring?

                    Primary Outcome

                    MeasureDescriptionTime Frame
                    Number of participants with adverse event (AEs)Not SpecifiedPart 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)Not SpecifiedPart B: Screening (Day -42 to Day -14) up to 2 cycles (84 days) of AZD2284
                    Estimates of residence timeNot SpecifiedPart A: Up to Day 8 after dosing with AZD2287 on Day 1
                    Absorbed radiation doses for AZD2287 and AZD2284Not SpecifiedPart 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 AZD2275Not SpecifiedPart 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 imagesNot SpecifiedPart 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

                    MeasureDescriptionTime Frame
                    Overall Response Rate (ORR)Not SpecifiedUp to 12 months after the last dose of AZD2284
                    Proportion of participants with Prostate-Specific Antigen (PSA) 50Not SpecifiedUp to 12 months after the last dose of AZD2284
                    Proportion of participants with PSA90Not SpecifiedUp to 12 months after the last dose of AZD2284
                    Time to maximum PSA % declineNot SpecifiedUp to 12 months after the last dose of AZD2284
                    Duration of Response (DoR)Not SpecifiedUp to 12 months after the last dose of AZD2284
                    Radiographic Progression Free Survival (rPFS)Not SpecifiedUp to 12 months after the last dose of AZD2284
                    Overall Survival (OS)Not SpecifiedPart A: Up to Day 28; Part B: Up to 5 years
                    Pharmacokinetic ClearanceNot SpecifiedPart 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)Not SpecifiedPart A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days)
                    Maximum observed drug concentration (Cmax)Not SpecifiedPart A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days)
                    Half-life (t1/2)Not SpecifiedPart 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 aloneNot SpecifiedPart A: Up to Day 28; Part B: Up to Cycle 2 (each cycle is 42 days)
                    Number of participants with positive antidrug antibodies (ADAs)Not SpecifiedPart A dose exploration: Up to Day 28; Part B: Up to End of Trial (approximately 1 year)
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                    References

                    Clinical Trials Gov: A Phase I Study of [225Ac]-AZD2284 in Patients With Metastatic Castration-Resistant Prostate Cancer

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