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

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

Overview

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.

Detailed description

This is a first-in-human modular, Phase I/IIa, open-label, multi-centre study of AZD0516 in participants with metastatic prostate cancer. The study will consist of individual modules, each evaluating the safety, tolerability, preliminary efficacy, PK, pharmacodynamic, and immunogenicity of AZD0516.

Module 1: Evaluates AZD0516 as monotherapy. It may include 3 parts, Part A- Dose Escalation, Part B- Dose Optimisation, and Part C- Efficacy Expansion.

Module 2: Evaluates AZD0516 in combination with AZD9574. It may include 2 parts, Part A - Dose Escalation and Part B Dose Optimisation.

Interventions

• Drug AZD0516
  AZD0516 will be administered via intravenous infusion.
• Drug AZD9574
  AZD9574 will be administered orally.

Primary outcome measures

• 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) [Time frame: From Day 1 up to approximately 3 years]
• Module 1 and 2: Part A: Number of participants with Dose Limiting Toxicities (DLTs) [Time frame: From Day 1 up to end of DLT period (approximately 21 days)]
• Module 1: Parts B and C and Module 2: Part B: Percentage of participants with Prostate-Specific Antigen (PSA) 50 response rate [Time frame: Up to approximately 2 years]

Secondary outcome measures (12)

• Module 1 and 2: Part A: Percentage of participants with PSA50 response rate [Time frame: Up to approximately 2 years]
• Module 1 and 2: Parts A, B and C: Percentage of participants with PSA90 response rate [Time frame: Up to approximately 2 years]
• Module 1 and 2: Parts A, B and C: Time to PSA 50 response (TTPSA50) [Time frame: Up to approximately 2 years]
• Module 1 and 2: Parts A, B and C: Time to PSA response (TTPSA90) [Time frame: Up to approximately 2 years]
• Module 1 and 2: Parts A, B and C: Duration of PSA response 50 (DoPSA50) [Time frame: Up to approximately 2 years]
• Module 1 and 2: Parts A, B and C: Duration of PSA response 90 (DoPSA90) [Time frame: Up to approximately 2 years]
• Module 1 and 2: Parts A, B and C: Percentage of participants with Durable PSA response rate 50 (DRRPSA50) [Time frame: Up approximately 2 years]
• Module 1 and 2: Parts A, B and C: Percentage of participants with Durable PSA response rate 90 (DRRPSA90) [Time frame: Up to approximately 2 years]
• Module 1 and 2: Parts A, B and C: Time to PSA Progression (TTPSA) [Time frame: Up to approximately 2 years]
• Module 1 and 2: Parts A, B and C: Percentage change from baseline in PSA levels [Time frame: Up to approximately 2 years]
• Module 1 and 2: Parts A, B and C: Percentage of participants with Overall Response Rate (ORR) [Time frame: Up to approximately 3 years]
• Module 1 and 2: Parts A, B and C: Percentage of participants with Best Overall Response (BOR) [Time frame: Up to approximately 3 years]

Eligibility criteria

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:

• 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).
• 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).
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• Research Site — Fayetteville
• Research Site — Los Angeles
• Research Site — Towson
• Research Site — Boston
• Research Site — Ann Arbor
• Research Site — Detroit
• Research Site — Buffalo
• Research Site — New York
• … and 3 more centers

Spain · 8 centers

• Research Site — Barcelona
• Research Site — Barcelona
• Research Site — Barcelona
• Research Site — L'Hospitalet de Llobregat
• Research Site — Madrid
• Research Site — Pamplona
• Research Site — Santander
• Research Site — Valencia

Italy · 6 centers

• Research Site — Milan
• Research Site — Milan
• Research Site — Milan
• Research Site — Naples
• Research Site — Roma
• Research Site — Rozzano

France · 5 centers

• Research Site — Lyon
• Research Site — Montpellier
• Research Site — Saint-Herblain
• Research Site — Suresnes
• Research Site — Villejuif

South Korea · 5 centers

• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul

United Kingdom · 5 centers

• Research Site — Cambridge
• Research Site — London
• Research Site — London
• Research Site — Plymouth
• Research Site — Sutton

Brazil · 3 centers

• Research Site — Barretos
• Research Site — Porto Alegre
• Research Site — São Paulo

China · 3 centers

• Research Site — Changsha
• Research Site — Chengdu
• Research Site — Wuhan

Japan · 3 centers

• Research Site — Chūōku
• Research Site — Kashiwa
• Research Site — Kōtoku

Poland · 3 centers

• Research Site — Koszalin
• Research Site — Piotrkow Trybunalski
• Research Site — Przemyśl

Identifiers

NCT: NCT07181161 · D9520C00001 · 2024-520026-11-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗