Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Participant will receive Saruparib (AZD5305) once daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days)

Participant will receive Saruparib (AZD5305) once daily + darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days).

No study treatment is to be taken by the participants in this arm. Radical prostatectomy should be performed as per local practice

Participant will receive darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days).

Saruparib (AZD5305) given orally once daily

Saruparib (AZD5305)

Darolutamide tablet is 300mg, given BD orally, twice daily- total dose 1200mg

Darolutamide

No Treatment

AstraZeneca Clinical Study Information Center

A Study to Investigate the Biological Effects of Saruparib (AZD5305) Alone, Darolutamide Alone, and in Combination Given Prior to Radical Prostatectomy in Men with Newly Diagnosed Prostate Cancer (ASCERTAIN)

An Open-label, Randomised, Phase-I, Multi-Centre Study to Investigate the Biological Effects of Saruparib (AZD5305) alone, Darolutamide alone, and in Combination Given Prior to Radical Prostatectomy in Men with Newly Diagnosed Prostate Cancer (ASCERTAIN)

A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.

An Open-label, Randomised, Phase-I, Multi-Centre Study to Investigate the Biological Effects of Saruparib (AZD5305) Alone, Darolutamide Alone, and in Combination Given Prior to Radical Prostatectomy in Men With Newly Diagnosed Prostate Cancer (ASCERTAIN)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal

Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved

To assess the effects of study treatment on γH2AX change in participants with localised prostate cancer

To assess the safety and tolerability of study treatment in participants with localised prostate cancer

To assess the safety of study treatment in participants with localised prostate cancer

To assess the impact of study treatment on surgical feasibility in participants with localised prostate cancer

To assess the effects of study treatment on Ki-67 change in participants with localised prostate cancer

AstraZeneca

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Fulvestrant

Exemestane

Letrozole

Palbociclib

Anastrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Protein Kinase Inhibitors

participants will receive saruparib (AZD5305) orally and camizestrant orally

agents are indicated below and should follow local guidelines:

* Physician's Choice CDK4/6i:

  * abemaciclib orally, or
  * ribociclib orally, or
  * palbociclib orally.
* Physician's Choice ET:

  * fulvestrant intramuscularly, or
  * One of the following AIs:

    * letrozole orally, or
    * anastrozole orally, or
    * exemestane orally

participants will receive camizestrant orally. Agents for CDK4/6i treatment are indicated above and should follow local guidelines

Saruparib (AZD5305) is a potent and selective inhibitor of PARP1, with minimal effect on PARP2.

Camizestrant (AZD9833) is an orally bioavailable, next generation SERD with non-clinical and clinical activity in both ESR1 mutant and wild type settings .

Camizestrant

Abemaciclib

Ribociclib

The primary objective of the study is to measure efficacy of saruparib (AZD5305) plus camizestrant compared with physician's choice CDK4/6i plus ET in patients with BRCA1, BRCA2, or PALB2m, HR-positive, HER2-negative (defined as IHC 0, 1+, 2+/ ISH non-amplified) advanced breast cancer.

Approximately 2,620 participants will be screened to achieve approximately 500 participants randomised to study intervention.

Participants will be randomised in a 2:2:1 ratio to one of the following intervention groups:

* Arm 1: saruparib (AZD5305) plus camizestrant
* Arm 2: Physician's choice CDK4/6i plus physician's choice ET
* Arm 3: Physician's choice CDK4/6i plus camizestrant Treatment continues until BICR-confirmed disease progression, unacceptable toxicity occurs, or the participant withdraws consent.

Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer

A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant Compared With Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients With BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

PFS is defined as time from randomisation until progression per RECIST v1.1 as assessed by BICR, or death due to any cause.

OS is defined as the time from randomisation until the date of death due to any cause.

PFS2 is defined as the time from randomisation to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.

Time to chemotherapy is defined as time from randomisation until the start date of the first subsequent chemotherapy treatment after discontinuation of randomised treatment (censoring participants who died prior to initiation of chemotherapy).

ORR is defined as the proportion of participants who have a complete or parial response, as determined by BICR per RECIST v1.1.

DoR is defined as the time from the date of first documented response until date of documented progression per RECIST v1.1 as assessed by BICR, or death due to any cause.

Proportion of all dosed participants reporting different levels of severity of diarrhoea as measured by the diarrhoea single item (EORTC IL237/IL239/IL240) and different levels of severity of abdominal pain as measured by the abdominal pain single item (EORTC IL237/IL239/IL240).

This scale includes 2 items asking participants to report overall health and overall quality of life in the past week. Both items are measured on a 6-point verbal rating scale ranging from Very Poor to Excellent. Single item scores are averaged to calculate a subscale score that is transformed to range from 0 to 100, where higher scores indicate better global health status/QoL.

Samples will be tested by a CDx to confirm BRCA1/2 and PALB2 gene mutation status

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.	NCT05938270	Prostate Cancer	Saruparib (AZD5... Darolutamide No Treatment	18 Years -	AstraZeneca
A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.	NCT05938270	Prostate Cancer	Saruparib (AZD5... Darolutamide No Treatment	18 Years -	AstraZeneca
Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer	NCT06380751	Advanced Breast...	Saruparib (AZD5... Camizestrant Abemaciclib Ribociclib Palbociclib Fulvestrant Letrozole Anastrozole Exemestane	18 Years - 130 Years	AstraZeneca
A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.	NCT05938270	Prostate Cancer	Saruparib (AZD5... Darolutamide No Treatment	18 Years -	AstraZeneca

Spots Global Cancer Trial Database for saruparib (azd5305)