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PARP inhibition

CompoundSaruparib

Area under investigation

Advanced solid tumors, HR-positive/HER2-negative breast cancer, Localized prostate cancer, mCRPC, mHSPC, Ovarian cancer, Pancreatic cancer, TNBC, NSCLC, SCLC, BRCAm or PALB2m breast cancer

Scientific PillarDNA Damage Response

 

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EvoPAR-Prostate01 trial overview

Tumor

mHSPC de novo or recurrent

Trial Identifier

NCT06120491

Phase

III

Regimen

Saruparib + ARPI; placebo + ARPI

Visit ct.gov

Study Design

Inclusion criteria

The key inclusion criteria are –

  • Aged ≥18 years
  • Histologically documented prostate adenocarcinoma (de novo or recurrent mHSPC)
  • Metastatic disease as documented by the investigator prior to randomization, with clear evidence of ≥1 bone lesion and/or ≥1 soft tissue lesion that is suitable for repeated assessment with CT and/or MRI
  • Participant is receiving ADT with a GnRH analog or has undergone bilateral orchiectomy starting ≥14 days and <4 months prior to randomization
  • ECOG PS 0-1 with no deterioration over the 2 weeks prior to randomization
  • Provision of FFPE tumor tissue sample and blood sample (for ctDNA)
  • Confirmed HRRm status by central tumor tissue and/or ctDNA test is required to determine cohort eligibility
  • Adequate organ and bone marrow function as described in study protocol
  • Participants must not father children or donate sperm from signing informed consent form, during the study intervention and for 6 months after the last dose of study intervention
  • Participants must use a condom from signing informed consent form, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners

 

Reference:

Study NCT06120491. ClinicalTrials.gov website.

Exclusion criteria

The key exclusion criteria are –

  • Participants with a history of MDS/AML or with features suggestive of MDS/AML
  • Participants with any known predisposition to bleeding
  • Any history of persisting (>2 weeks) severe cytopenia
  • Refractory nausea and vomiting, chronic GI diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib and/or the assigned ARPI
  • History of another primary malignancy, with exceptions
  • 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 the study intervention
  • Cardiac criteria, including history of arrhythmia and cardiovascular disease
  • Any prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with exceptions
  • Prior treatment within 14 days with blood product support or growth factor support
  • Participants who are unevaluable for both bone and soft tissue progression

EvoPAR-Prostate01 Overview Modal

EvoPAR-Prostate01 trial overview

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Target Overview

Poly [ADP-ribose] polymerases (PARPs) are a group of proteins known to be involved in the repair of single-strand breaks in DNA.1

A healthy cell’s DNA undergoes damage every day, with approximately 10,000 spontaneous single-strand breaks that require repair.1

Inhibition of PARP1 with AZD5305 leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks. In tumor cells that already have compromised DNA repair mechanisms (such as loss of BRCA1 or BRCA2 function, affecting double-strand break repair), inhibition of PARP leads to excessive accumulation of DNA damage and may cause death of the cell.1,2

Compound Overview

Saruparib (AZD5305) is an investigational, new generation PARP inhibitor. It is designed to selectively inhibit and trap PARP1, enabling efficacy, while broadening the opportunity for clinical benefit by allowing combination approaches with different treatment options.3,4

Mechanism of Action

  • Mechanism of Action
  • Mechanism of Action

References

1. Underhill C, Toulmonde M, Bonnefoi H. Ann Oncol. 2011;22(2):268-279. 2. Yelamos J, Farres J, Llacuna L, et al. Am J Cancer Res. 2011;1(3):328-346. 3. Farrés J, Martín-Caballero J, Martínez C, et al. Blood. 2013;122(1):44-54. 4. Farrés J, Llacuna L, Martín-Caballero J, et al. Cell Death Differ. 2015;22(7):1144-1157.

 

Loading......

EvoPAR-Prostate01 trial overview

Tumor

mHSPC de novo or recurrent

Trial Identifier

NCT06120491

Phase

III

Regimen

Saruparib + ARPI; placebo + ARPI

Visit ct.gov

Study Design

Inclusion criteria

The key inclusion criteria are –

  • Aged ≥18 years
  • Histologically documented prostate adenocarcinoma (de novo or recurrent mHSPC)
  • Metastatic disease as documented by the investigator prior to randomization, with clear evidence of ≥1 bone lesion and/or ≥1 soft tissue lesion that is suitable for repeated assessment with CT and/or MRI
  • Participant is receiving ADT with a GnRH analog or has undergone bilateral orchiectomy starting ≥14 days and <4 months prior to randomization
  • ECOG PS 0-1 with no deterioration over the 2 weeks prior to randomization
  • Provision of FFPE tumor tissue sample and blood sample (for ctDNA)
  • Confirmed HRRm status by central tumor tissue and/or ctDNA test is required to determine cohort eligibility
  • Adequate organ and bone marrow function as described in study protocol
  • Participants must not father children or donate sperm from signing informed consent form, during the study intervention and for 6 months after the last dose of study intervention
  • Participants must use a condom from signing informed consent form, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners

 

Reference:

Study NCT06120491. ClinicalTrials.gov website.

Exclusion criteria

The key exclusion criteria are –

  • Participants with a history of MDS/AML or with features suggestive of MDS/AML
  • Participants with any known predisposition to bleeding
  • Any history of persisting (>2 weeks) severe cytopenia
  • Refractory nausea and vomiting, chronic GI diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib and/or the assigned ARPI
  • History of another primary malignancy, with exceptions
  • 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 the study intervention
  • Cardiac criteria, including history of arrhythmia and cardiovascular disease
  • Any prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with exceptions
  • Prior treatment within 14 days with blood product support or growth factor support
  • Participants who are unevaluable for both bone and soft tissue progression

EvoPAR-Prostate01 Overview Modal

EvoPAR-Prostate01 trial overview

Take me to ClinicalTrials.Gov

You are now leaving the AstraZeneca Oncology Portfolio.
You have selected a link that will take you to a site maintained by a third party.

Click ‘Cancel’ to return back or ‘Continue’ to proceed.

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Abbreviations

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  • ADP

    adenosine diphosphate

  • ADT

    androgen-deprivation therapy

  • AE

    adverse event

  • AML

    acute myeloid leukemia

  • ARPI

    androgen receptor pathway inhibitor

  • BRCA

    breast cancer susceptibility gene

  • ECOG PS

    Eastern Cooperative Oncology Group Performance Score

  • HRQoL

    health-related quality of life

  • HRRm

    homologous recombination repair gene mutation

  • MDS

    myelodysplastic syndrome

  • mHSPC

    metastatic hormone-sensitive prostate cancer

  • PARP

    poly (ADP-ribose) polymerase

  • pcARPI

    physician’s choice of androgen receptor pathway inhibitor

  • PCWG-3

    Prostate Cancer Clinical Trials Working Group 3

  • PFS2

    time to second progression or death

  • PRO

    patient-reported outcomes

  • PSA

    prostate-specific antigen

  • SAE

    serious adverse event

  • SSE-FS

    symptomatic skeletal event-free survival

  • TEAE

    treatment emergent adverse event

  • TFST

    time to first subsequent therapy

  • TTCR

    time to the first castration-resistant event

  • TTDF

    time to deterioration in fatigue

  • TTDPF

    time to deterioration in physical function

  • TTDUS

    time to deterioration in urinary symptoms

  • TTPP

    time to pain progression

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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