A Randomized, 2-cohort, Double-blind, Placebo-controlled, Phase III Study of AZD5305 in Combination with Physician's Choice New Hormonal Agents in Patients with HRRm and non-HRRm Metastatic Castration-Sensitive Prostate Cancer (EvoPAR-Prostate01)

This is a Phase III, 2-cohort, 2-arm, parallel-group, randomised, double-blind, placebo-controlled, multicentre, global study, assessing the efficacy and safety of AZD5305 + physician's choice NHA compared with placebo + physician's choice NHA in participants with mCSPC with and without HRRm.

Participant Population:
The target population of interest in this study is participants with mCSPC.

For more information, please visit: https://clinicaltrials.gov/study/NCT06120491

Inova Schar Cancer
8081 Innovation Park Drive
Fairfax VA 22031

Participants are eligible to be included in the study only if all of the following criteria apply:

• Age
  Male ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), at the time of signing the ICF.
• Type of Participant and Disease Characteristics
  • Histologically documented prostate adenocarcinoma which is de novo or recurrent and castration-sensitive. Participants with pathologic features of small cell, neuroendocrine, sarcomatoid, spindle cell, or signet cell histology are not eligible.
  • Metastatic disease as documented by the investigator prior to randomisation, with clear evidence of ≥ 1 bone lesion (defined as one lesion with positive uptake on bone scan) and/or ≥ 1 soft tissue lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment with CT and/or MRI.
    • Participants with metastatic disease identified by PSMA-PET only, will not be eligible.
    • Participants with disease limited to regional pelvic lymph nodes only are not eligible.
  • Participant is receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy starting ≥ 14 days and < 4 months prior to randomisation with no radiographic evidence of disease progression or rising PSA levels prior to first day of dosing. Participant must remain on ADT throughout the study and be a candidate for treatment with an NHA. Combination with first generation AR antagonists to counter testosterone flare is permitted until randomisation.
    • Note: Due to the interaction between relugolix and enzalutamide, this combination of ADT and NHA is not allowed. Relugolix is otherwise permitted.
  • ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomisation.
  • Minimum life expectancy of 6 months.
  • Adequate organ and bone marrow function.
  • Male participants:
    • Must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention. 
      • For participants wishing to father children, arrangement of donation of sperm prior to signing ICF must be made. Male participants may be rejected as a sperm donor after the study.
    • Must use a condom (with spermicide - where permitted) from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners. 
      • Female partners who are women of childbearing potential should use a highly effective method of contraception for the same period (See Appendix G).

Participants are excluded from the study if any of the following criteria apply:
 

• Medical Conditions
  • Participants with a history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). Specific screening for MDS/AML is not required.
  • Participants with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy).
  • Any history of persisting (> 2 weeks) severe cytopenia due to any cause (eg, absolute neutrophil count < 0.5 × 109/L or platelets < 50 × 109/L).
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305 and/or the assigned NHA.
  • History of another primary malignancy, with the following exceptions:
    • Adequately resected non-melanoma skin cancer.
    • Curatively treated in situ disease.
    • Malignancy treated with curative intent ≥ 3 years before the first dose of study intervention, and with no known active disease during the intervening time period.
  • Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy.
  • Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention. 
  • History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. 
  • Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the AstraZeneca study physician.
  • Presence of clinically significant valvular heart disease.
  • Evidence of active and uncontrolled hepatitis B and/or hepatitis C.
  • Evidence of active and uncontrolled HIV infection.
  • Active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
• As judged by the investigator, any other evidence of diseases, such as severe or uncontrolled systemic diseases or active uncontrolled infections, including but not limited to uncontrolled major seizure disorder, active bleeding diseases, superior vena cava syndrome, or history of allogenic organ transplant, which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or would jeopardise compliance with the protocol.