Study of AZD0516 as Monotherapy and in Combination in Participants With Metastatic Prostate Cancer

NCT07181161
clinicaltrials.gov
Phase
Phase 1/Phase 2
clinicaltrials.gov
Recruitment status
Recruiting
clinicaltrials.gov
Participants
283
clinicaltrials.gov
Lead sponsor
AstraZeneca
clinicaltrials.gov
Start date
2025-10-01
clinicaltrials.gov
Number of sites
52
clinicaltrials.gov

Summary
The main purpose of this study is to assess the safety and tolerability of AZD0516 as monotherapy and/or in combination with other anti-cancer agents for treatment of metastatic prostate cancer.
clinicaltrials.gov
Acronym
SEACLIFF
clinicaltrials.gov
Short title
Study of AZD0516 as Monotherapy and in Combination in Participants With Metastatic Prostate Cancer
clinicaltrials.gov
Official title
A Modular Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0516 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Metastatic Prostate Cancer
clinicaltrials.gov

Control arm
Open label
clinicaltrials.gov
Registry reports results
No
clinicaltrials.gov
Listing at source
Listed
clinicaltrials.gov
Recruitment status
Recruiting
clinicaltrials.gov
Phase
Phase 1/Phase 2
clinicaltrials.gov
Study type
Interventional
clinicaltrials.gov

Completion date
2029-01-18
clinicaltrials.gov
First posted
2025-09-18
clinicaltrials.gov
Registry last updated
2026-10-22
clinicaltrials.gov
Primary completion date
2029-01-18
clinicaltrials.gov
Start date
2025-10-01
clinicaltrials.gov

Participants
283
clinicaltrials.gov
Participant count basis
Estimated
clinicaltrials.gov
Planned participants
283
clinicaltrials.gov
Protocol amendments
1
clinicaltrials.gov
Number of sites
52
clinicaltrials.gov

Data monitoring committee
No
clinicaltrials.gov
Registry sponsor category
Industry
clinicaltrials.gov
Lead sponsor
AstraZeneca
clinicaltrials.gov
Source registry
ClinicalTrials.gov
clinicaltrials.gov

Registry ID
NCT07181161
clinicaltrials.gov
ClinicalTrials.gov ID
NCT07181161
clinicaltrials.gov
Registry record
Open registry record
clinicaltrials.gov

Allocation
Randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Module 1 and 2: Parts A and B: Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interests (AESIs)

    Timeframe: From Day 1 up to approximately 3 years

    Part A: To assess the safety and tolerability and to determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) of AZD0516 as monotherapy and in combination with anti-cancer agents. Part B: To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents.

  2. Module 1 and 2: Part A: Number of participants with Dose Limiting Toxicities (DLTs)

    Timeframe: From Day 1 up to end of DLT period (approximately 21 days)

    To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents.

  3. Module 1: Parts B and C and Module 2: Part B: Percentage of participants with Prostate-Specific Antigen (PSA) 50 response rate

    Timeframe: Up to approximately 2 years

    The PSA50 response rate is defined as the percentage of participants achieving ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result.

  1. Module 1 and 2: Part A: Percentage of participants with PSA50 response rate

    Timeframe: Up to approximately 2 years

    The PSA50 response rate is defined as the percentage of participants achieving ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result.

  2. Module 1 and 2: Parts A, B and C: Percentage of participants with PSA90 response rate

    Timeframe: Up to approximately 2 years

    The PSA90 response rate is defined as the percentage of participants with a confirmed ≥ 90% decrease in PSA from baseline to the lowest post-baseline PSA result.

  3. Module 1 and 2: Parts A, B and C: Time to PSA 50 response (TTPSA50)

    Timeframe: Up to approximately 2 years

    The TTPSA response is defined as the time from the date of first dose of study intervention until the date of first documented PSA50 response (≥ 50% decrease in PSA from baseline, respectively) that is confirmed by a second consecutive PSA assessment at least 3 weeks later.

  4. Module 1 and 2: Parts A, B and C: Time to PSA response (TTPSA90)

    Timeframe: Up to approximately 2 years

    The TTPSA response is defined as the time from the date of first dose of study intervention until the date of first documented PSA90 response (≥ 90% decrease in PSA from baseline, respectively) that is confirmed by a second consecutive PSA assessment at least 3 weeks later.

  5. Module 1 and 2: Parts A, B and C: Duration of PSA response 50 (DoPSA50)

    Timeframe: Up to approximately 2 years

    The DoPSA50 is defined as the time from the date of first documented PSA50 response, that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, until the date of documented PSA progression.

  6. Module 1 and 2: Parts A, B and C: Duration of PSA response 90 (DoPSA90)

    Timeframe: Up to approximately 2 years

    The DoPSA90 is defined as the time from the date of first documented PSA90 response, that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, until the date of documented PSA progression.

  7. Module 1 and 2: Parts A, B and C: Percentage of participants with Durable PSA response rate 50 (DRRPSA50)

    Timeframe: Up approximately 2 years

    The DRRPSA50 is defined as the percentage of participants who have a documented PSA50 response that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, with a duration of at least 6 months.

  8. Module 1 and 2: Parts A, B and C: Percentage of participants with Durable PSA response rate 90 (DRRPSA90)

    Timeframe: Up to approximately 2 years

    The DRRPSA90 is defined as the percentage of participants who have a documented PSA90 response that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, with a duration of at least 6 months.

  9. Module 1 and 2: Parts A, B and C: Time to PSA Progression (TTPSA)

    Timeframe: Up to approximately 2 years

    TTPSA progression is defined as time from the date of first dose of study intervention until the date of documented PSA progression or the last PSA result in the absence of progression.

  10. Module 1 and 2: Parts A, B and C: Percentage change from baseline in PSA levels

    Timeframe: Up to approximately 2 years

    The percentage change from baseline in PSA levels will be assessed.

  11. Module 1 and 2: Parts A, B and C: Percentage of participants with Overall Response Rate (ORR)

    Timeframe: Up to approximately 3 years

    The ORR is defined as the percentage of participants with a confirmed tumour response of Complete Response (CR) or Partial Response (PR).

  12. Module 1 and 2: Parts A, B and C: Percentage of participants with Best Overall Response (BOR)

    Timeframe: Up to approximately 3 years

    The BOR is defined as the best overall visit response achieved by participant.

  13. Module 1 and 2: Parts A, B and C: Duration of Response (DoR)

    Timeframe: Up to approximately 3 years

    The DoR is defined as the time from the date of first documented objective response (which is subsequently confirmed) until the date of radiographic disease progression or censoring.

  14. Module 1 and 2: Parts A, B and C: Percentage of participants with Durable Response Rate (DRR)

    Timeframe: Up to approximately 3 years

    The DRR is defined as the percentage of participants who have a confirmed response with a duration of at least 6 months.

  15. Module 1 and 2: Parts A, B and C: Percentage of participants with Disease Control Rate (DCR)

    Timeframe: Up to approximately 3 years

    The DCR is defined as the percentage of participants who have a BOR of confirmed CR or PR or Stable Disease (SD).

  16. Module 1 and 2: Parts A, B and C: Time to Response (TTR)

    Timeframe: Up to approximately 3 years

    The TTR is defined as the time from the date of first dose of study intervention until the date of first documented objective response, which is subsequently confirmed.

  17. Module 1 and 2: Parts A, B and C: Percentage Change in Tumour Size

    Timeframe: Up to approximately 3 years

    The best percentage change from baseline in tumour size is the largest decrease (or smallest increase) from baseline for a participant, using response evaluation criteria in solid tumors (RECIST) v1.1 assessments.

  18. Module 1 and 2: Parts A, B and C: Radiographic Progression-free Survival (rPFS)

    Timeframe: Up to approximately 3 years

    rPFS is defined as the time from date of first dose of study intervention until the date of objective disease progression according to RECIST v1.1 (for soft tissue disease) and prostate cancer working group 3 (PCWG3) criteria (for bone disease) as assessed by the investigator at the local site, or death (by any cause in the absence of progression).

  19. Module 1 and 2: Parts A, B and C: Overall Survival (OS)

    Timeframe: Up to approximately 3 years

    OS is defined as the time from date of first dose of study intervention until death due to any cause.

  20. Module 1 and 2: Part A and B: Changes in Plasma concentration of AZD0516

    Timeframe: From Day 1 up to approximately 3 years

    To characterise the pharmacokinetics (PK) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

  21. Module 1 and 2: Parts A and B: Area under concentration-time curve (AUC)

    Timeframe: From Day 1 up to approximately 3 years

    To characterise the PK (AUC) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

  22. Module 1 and 2: Parts A and B: Maximum observed drug concentration (Cmax)

    Timeframe: From Day 1 up to approximately 3 years

    To characterise the PK (Cmax) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

  23. Module 1 and 2: Parts A and B: Time to reach maximum observed concentration (tmax)

    Timeframe: From Day 1 up to approximately 3 years

    To characterise the PK (tmax) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

  24. Module 1 and 2: Parts A and B: Tobal Body Clearance (CL)

    Timeframe: From Day 1 up to approximately 3 years

    To characterise the PK (CL) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

  25. Module 1 and 2: Parts A and B: Half-life (t1/2)

    Timeframe: From Day 1 up to approximately 3 years

    To characterise the PK (t1/2) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

And 6 more, listed on the interactive page.

Sources for outcomes
clinicaltrials.gov

Sex
Male
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
130 Years
Healthy volunteers
No

Main Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of metastatic adenocarcinoma of the prostate. Focal high grade neuroendocrine features are permitted.

  • Measurable PSA ≥ 1 μg/L (≥ 1 ng/mL).

  • Surgically or medically castrated with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within ≤ 28 days before treatment allocation. Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone (GnRH) modulator for participants who have not undergone bilateral orchiectomy must be initiated at least 2 weeks prior to consent and must continue throughout the study.

  • Eastern cooperative oncology group (ECOG) performance status of 0 or 1.

  • Adequate organ and marrow function in the absence of blood transfusion or growth factor support (within 21 days prior to the scheduled first dose of study intervention).

  • Provision of baseline archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tumour sample is mandatory.

  • Documented current evidence of metastatic prostate cancer

  • Life expectancy of at least 12 weeks in the opinion of the investigator

  • Documented mCRPC progression at screening as assessed by the investigator with at least one of the following criteria:

    1. PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the screening visit should be ≥ 1 μg/L (1 ng/mL).
    2. Radiographic disease progression in soft tissue based on response evaluation criteria in solid tumors (RECIST) v1.1 criteria with or without PSA progression as per prostate cancer working group 3 (PCWG3).
    3. Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on a bone scan as per PCWG3 with or without PSA progression.

Main Exclusion Criteria:

  • Cancer related spinal cord compression, or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to study enrolment.
  • History of leptomeningeal carcinomatosis.
  • Unresolved toxicities of Grade ≥ 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from prior therapy (excluding vitiligo, alopecia, and endocrine disorders that are controlled with replacement hormone therapy).
  • Uncontrolled intercurrent illness within the last 12 months.
  • Cardiovascular disorder (History of arrhythmia, uncontrolled hypertension, symptomatic hypotension, history of brain perfusion problems, symptomatic heart failure, prior or current cardiomyopathy, severe valvular heart disease)
  • History of malignancy
  • History of non-infectious interstitial lung disease (ILD)/pneumonitis
  • Active infection exclusions, including tuberculosis and infections with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV).
  • Any known predisposition to bleeding
  • Clinically severe pulmonary compromise
  • Participants with Myelodysplastic syndrome (MDS)/Acute Myeloid Leukemia (AML) or with features suggestive of MDS/AML.
  • Previous treatment with a STEAP2 targeting modality, chemotherapeutic agent that inhibits topoisomerase activity or metabolic enzymes.
Sources for eligibility
clinicaltrials.gov

  • Research SiteFayetteville, United StatesRecruiting
  • Research SiteLos Angeles, United StatesRecruiting
  • Research SiteTowson, United StatesSuspended
  • Research SiteBoston, United StatesRecruiting
  • Research SiteAnn Arbor, United StatesRecruiting
  • Research SiteDetroit, United StatesRecruiting
  • Research SiteBuffalo, United StatesSuspended
  • Research SiteNew York, United StatesRecruiting
  • Research SiteProvidence, United StatesRecruiting
  • Research SiteMyrtle Beach, United StatesRecruiting
  • Research SiteHouston, United StatesRecruiting
  • Research SiteBarretos, BrazilNot yet recruiting
  • Research SitePorto Alegre, BrazilNot yet recruiting
  • Research SiteSão Paulo, BrazilNot yet recruiting
  • Research SiteChangsha, ChinaNot yet recruiting
  • Research SiteChengdu, ChinaNot yet recruiting
  • Research SiteWuhan, ChinaNot yet recruiting
  • Research SiteLyon, FranceWithdrawn
  • Research SiteMontpellier, FranceWithdrawn
  • Research SiteSaint-Herblain, FranceWithdrawn
  • Research SiteSuresnes, FranceWithdrawn
  • Research SiteVillejuif, FranceWithdrawn
  • Research SiteMilan, ItalyNot yet recruiting
  • Research SiteMilan, ItalyNot yet recruiting
  • Research SiteMilan, ItalyNot yet recruiting

And 27 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-520026-11-00
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Collaborators (1)

Lead sponsors (1)

Conditions (2)

Targets (2)