Clinical Trial 23757

• Overview

  Study Title:

  A Randomised, Double-blind, Placebo-controlled, Phase III Study of Adjuvant Saruparib (AZD5305) in Patients with BRCAm Localised High-Risk Prostate Cancer Receiving Radiotherapy with Androgen Deprivation Therapy (EvoPAR-Prostate02)

  Summary:

  The purpose of the study is to demonstrate superiority of Saruparib (AZD5305) relative to placebo added to a standard radiation therapy (RT) + androgen deprivation therapy (ADT) regimen by assessment of metastases-free survival in participants with high-risk and very high-risk localised/locally advanced prostate cancer with a breast cancer gene mutation (BRCAm).

  Objective:

  Primary objective: - To demonstrate the superiority of adjuvant saruparib relative to placebo added to standard ADT therapy in participants with high-risk and very high-risk (localised/locally advanced) prostate cancer with a BRCA1/2 mutation receiving either primary or salvage RT (Cohort A) by assessment of MFS using standard clinical imaging, by BICR. - To demonstrate the superiority of adjuvant saruparib relative to placebo added to standard ADT therapy plus abiraterone in participants with localised very high-risk prostate cancer with a BRCA1/2 mutation receiving primary RT (Cohort B) by assessment of MFS using standard clinical imaging, by BICR. Key Secondary objective: - To demonstrate the superiority of adjuvant saruparib relative to placebo added to standard ADT therapy for participants in Cohort A by assessment of OS. - To demonstrate the superiority of adjuvant saruparib relative to placebo added to standard ADT therapy plus abiraterone for participants in Cohort B by assessment of OS.

• Treatments

  Therapies:

  Androgen deprivation therapy (ADT); PARP inhibitor

  Medications:

  ADT (); Abiraterone (); Placebo (); Saruparib ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Male participants with a histologically documented diagnosis of prostate adenocarcinoma.
  • Newly diagnosed high-risk and very high-risk (localised/locally advanced) prostate cancer or a high-risk biochemical recurrence (BCR) following radical prostatectomy.
  • Provision of a formalin fixed and paraffin embedded (FFPE) tumour tissue sample.
  • Confirmed BRCA1 or BRCA2 mutation status by central tumour tissue is required for enrolment.
  • Participants required to have a computed tomography (CT) or magnetic resonance imaging (MRI) and a bone scan following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0).
  • Participants required to have a prostate-specific membrane antigen-positron emission tomography (PSMA-PET) following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomization.
  • Minimum life expectancy of 12 months.
  • Adequate organ and bone marrow function as described in study protocol.
  • All participants will have received either primary or salvage RT. Participants must be eligible for randomization within 10 months of initial diagnosis (de novo or BCR). Radiotherapy administered to the prostate (± pelvis) either in the primary or salvage setting must be delivered with curative intent. Use of metastases-directed therapy, as part of the RT radiation plan, is permitted as localised RT treatment for a metastatic lesion(s) outside the pelvis.
  • All participants will have received a planned regimen of ADT with a gonadotropin releasing hormone (GnRH) analogue.
  • Participants must not father children or donate sperm from signing informed consent form (ICF), during the study intervention and for 6 months after the last dose of study intervention.
  • Participants 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.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Participants with a history of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
  • Participants with any known predisposition to bleeding [e.g., active peptic ulceration, recent (within 6 months) hemorrhagic stroke, proliferative diabetic retinopathy].
  • Any history of persisting (> 2 weeks) severe cytopenia due to any cause.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib and/or abiraterone.
  • History of another primary malignancy, with exceptions.
  • Persistent toxicities [Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2] caused by previous anticancer therapy.
  • Cardiac criteria, including history of arrhythmia and cardiovascular disease.
  • Evidence of active and uncontrolled hepatitis B and/or hepatitis C.
  • Evidence of active and uncontrolled human immunodeficiency virus (HIV) infection.
  • Active tuberculosis infection.
  • Any prior chemotherapy (i.e., docetaxel) or immunotherapy; any prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor.
  • Prior treatment within 14 days with blood product support or growth factor support.
  • Concomitant use of strong inducers and inhibitors of CYP3A4 (applies to saruparib and abiraterone) or herbal supplements within 21 days or at least 5 half-lives (whichever is longer), of randomization.
  • Concomitant use of drugs that are known to prolong QT and have a known risk of Torsades de Pointes (TdP).
  • Participants with a known hypersensitivity to saruparib or any excipients of these products.

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