AZD5305 for Prostate Cancer

(EvoPAR-PR01 Trial)

Recruiting at 321 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: GnRH analogues

Disqualifiers: MDS/AML, Bleeding predisposition, Severe cytopenia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: up to approximately 50 months

1800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, Saruparib (AZD5305), to determine if it can slow the progression of metastatic castration-sensitive prostate cancer (mCSPC). Participants will receive either Saruparib with another treatment chosen by their doctor or a placebo (inactive treatment) with the doctor's choice. The trial aims to determine if Saruparib can more effectively prevent cancer from worsening compared to the placebo. Men with prostate cancer that has spread to bones or soft tissue and who are already on hormone therapy might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have had prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with some exceptions. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study used AZD5305, also known as Saruparib, with hormone therapies and found it safe. Most participants tolerated it well, with only a few requiring dosage adjustments or pauses. This suggests AZD5305 might be safe for patients. However, since individual reactions can vary, discussing participation in any trial with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about Saruparib (AZD5305) because it's a new kind of treatment for prostate cancer, focusing on a different mechanism. Unlike standard drugs like Abiraterone, Darolutamide, or Enzalutamide, which target hormone pathways, Saruparib is a PARP inhibitor. It works by blocking a protein that cancer cells rely on to repair their DNA, potentially leading to more effective cancer cell death. This novel approach offers hope for better outcomes, especially for patients who don't respond well to existing hormone therapies.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that AZD5305, also known as Saruparib, is a promising treatment for prostate cancer. It blocks a protein called PARP1, which cancer cells use for self-repair. This trial will test Saruparib combined with a physician's choice of hormone therapy (Abiraterone, Darolutamide, or Enzalutamide) in one of the treatment arms. In early studies, Saruparib led to a complete response in 75% of cases, meaning no signs of cancer were found, compared to 37% with older drugs. Other research has demonstrated that it can be safely used with hormone therapies without causing many side effects. These findings suggest that Saruparib could be a strong option for treating prostate cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Arun Azad

Principal Investigator

Peter MacCallum Cancer Centre, Australia

Kim Nguyen Chi, MD

Principal Investigator

BC Cancer, Canada

Are You a Good Fit for This Trial?

This trial is for men over 18 with metastatic castration-sensitive prostate cancer, showing at least one bone or soft tissue lesion. They must have started hormone therapy recently and be in good physical condition. Men with certain types of aggressive cancer cells, previous severe blood disorders, or prior treatment for metastatic cancer are excluded.

Inclusion Criteria

As a participant, you must abstain from fathering children or donating sperm for the duration of the study intervention and 6 months following its completion.

My cancer has spread, and I have at least one bone or soft tissue lesion that can be monitored with scans.

My cancer has a specific genetic change confirmed by tests.

Exclusion Criteria

I have not received blood products or growth factors in the last 14 days.

I have had treatment or surgery for advanced prostate cancer, with some exceptions.

I cannot take pills due to severe nausea, vomiting, or other serious gut issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Saruparib (AZD5305) or placebo in combination with physician's choice new hormonal agents until disease progression or treatment discontinuation

up to approximately 50 months

Follow-up

Participants are monitored for survival and other outcomes after treatment

up to approximately 90 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• AZD5305
• Darolutamide
• Enzalutamide
• Placebo

Trial Overview The study aims to see if AZD5305 combined with a hormonal agent chosen by the physician works better than a placebo combined with the same hormonal agent. The main goal is to check if this combination can slow down the progression of prostate cancer as seen on imaging tests.

How Is the Trial Designed?

Group I: Arm 1: Saruparib (AZD5305) + Physician's Choice NHA Experimental Treatment 4 Interventions

Saruparib (AZD5305) + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)

Group II: Arm 2: Placebo + Physician's Choice NHA Placebo Group 4 Interventions

Placebo + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In the ARAMIS trial, darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% compared to placebo in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

The overall survival benefit of darolutamide was consistent across patients with varying numbers of comorbidities and concomitant medications, with similar rates of treatment-emergent adverse events compared to placebo, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial. Fizazi, K., Shore, ND., Smith, M., et al.[2023]

Docetaxel-based chemotherapy has been the standard treatment for metastatic castration-resistant prostate cancer (mCRPC), but new therapies like cabazitaxel, abiraterone acetate, and enzalutamide are now available, offering more options for patients.

The review highlights ongoing research into novel targeted agents and immunotherapies, which aim to overcome resistance mechanisms in prostate cancer, indicating a shift towards more personalized and effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New perspectives in the therapy of castration resistant prostate cancer. Rescigno, P., Buonerba, C., Bellmunt, J., et al.[2019]

The phase II TOPARP-A clinical trial found that men with metastatic castration-resistant prostate cancer are more likely to respond to the PARP inhibitor olaparib if they have mutations in DNA damage repair genes.

This study is significant as it provides the first evidence for using molecular stratification to identify which patients may benefit most from olaparib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stratifying prostate patients for olaparib. [2015]

Rucaparib, a PARP inhibitor, has been granted accelerated approval for treating men with metastatic castration-resistant prostate cancer (mCRPC) who have BRCA1 or BRCA2 mutations, based on safety data from clinical trials involving 193 participants.

Common treatment-emergent adverse events (TEAEs) include gastrointestinal issues, fatigue, and anemia, with most being self-limiting; effective management of these TEAEs is crucial to maximize the benefits of rucaparib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for Management of Treatment-Emergent Adverse Events During Rucaparib Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. Labadie, BW., Morris, DS., Bryce, AH., et al.[2022]

The TALAPRO-2 study is a phase III clinical trial designed to evaluate the effectiveness of talazoparib combined with enzalutamide compared to placebo with enzalutamide in treating metastatic castration-resistant prostate cancer (mCRPC).

The study aims to determine if this combination therapy can significantly improve radiographic progression-free survival (rPFS) in patients with or without DNA damage response (DDR) alterations, potentially enhancing treatment outcomes for mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: TALAPRO-2 phase III study design. Agarwal, N., Azad, A., Shore, ND., et al.[2022]

In a phase II trial involving 28 patients with advanced castration-resistant prostate cancer, the oral Src-family kinase inhibitor AZD0530 was found to be well tolerated but showed limited clinical efficacy as a standalone treatment, with only 32% of patients experiencing transient PSA reductions.

The median progression-free survival was only 8 weeks, suggesting that while AZD0530 is safe for use in this patient population, further research is needed to explore its potential in earlier-stage prostate cancer or in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of the Src-kinase inhibitor AZD0530 in patients with advanced castration-resistant prostate cancer: a California Cancer Consortium study. Lara, PN., Longmate, J., Evans, CP., et al.[2021]

The TALAPRO-3 study is a phase III clinical trial designed to evaluate the effectiveness of combining talazoparib, a poly(ADP-ribose) polymerase inhibitor, with enzalutamide in patients with metastatic castration-sensitive prostate cancer (mCSPC) who have homologous recombination repair (HRR) gene alterations.

The primary goal of the study is to determine if this combination therapy can improve radiographic progression-free survival (rPFS) compared to enzalutamide alone, potentially offering a new treatment strategy for patients with specific genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TALAPRO-3 clinical trial protocol: phase III study of talazoparib plus enzalutamide in metastatic castration-sensitive prostate cancer. Agarwal, N., Saad, F., Azad, AA., et al.[2023]

The combination of AZD5363 and enzalutamide (ENZ) significantly delays the development of resistance in castrate-resistant prostate cancer (CRPC) by enhancing apoptosis and inducing cell cycle arrest, as shown in preclinical models.

AZD5363 alone demonstrated strong anti-tumor effects, and when combined with ENZ, it led to impressive tumor regression without recurrence, suggesting that this combination therapy could be more effective if administered earlier in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination AZD5363 with Enzalutamide Significantly Delays Enzalutamide-resistant Prostate Cancer in Preclinical Models. Toren, P., Kim, S., Cordonnier, T., et al.[2022]

In men with metastatic hormone-sensitive prostate cancer, enzalutamide, when combined with androgen-deprivation therapy, significantly prolonged radiographic progression-free survival compared to a placebo.

This finding highlights the efficacy of enzalutamide as an androgen-receptor inhibitor in improving outcomes for patients undergoing treatment for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eyeing Enzalutamide for Hormone-Sensitive Prostate Cancer. [2020]

Enzalutamide significantly improved radiographic progression-free survival (rPFS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer across various disease subgroups, including nonvisceral and visceral disease, as well as low- and high-volume bone disease.

The treatment was well tolerated, showing clinically significant benefits in overall survival (OS) for most subgroups, although the results were less definitive for patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. Evans, CP., Higano, CS., Keane, T., et al.[2022]

In the SPARTAN study, apalutamide combined with androgen deprivation therapy (ADT) led to rapid and significant reductions in prostate-specific antigen (PSA) levels in most patients, with 90% achieving at least a 50% reduction by 6 months, compared to only 1.5% in the placebo group.

Deep PSA responses (≥90% reduction or PSA ≤0.2 ng/ml) at 6 months were strongly linked to improved outcomes, including metastasis-free survival and overall survival, indicating that early PSA monitoring can be a valuable prognostic tool for patients with high-risk nonmetastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN. Saad, F., Small, EJ., Feng, FY., et al.[2022]

ARV-110 is a novel drug designed to target and degrade the androgen receptor, which is important in the progression of metastatic castration-resistant prostate cancer.

Preliminary clinical data suggest that ARV-110 is safe for use and demonstrates some effectiveness in treating men with this type of advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proof-of-Concept with PROTACs in Prostate Cancer. [2021]

In a large registry study involving 1976 patients with metastatic castration-resistant prostate cancer, sipuleucel-T immunotherapy demonstrated a median overall survival of 30.7 months, indicating its potential effectiveness in prolonging life for this patient group.

The treatment was associated with a low incidence of serious adverse events (3.9%) and cerebrovascular events (2.8%), suggesting that sipuleucel-T is a relatively safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. Higano, CS., Armstrong, AJ., Sartor, AO., et al.[2021]

Enzalutamide significantly improves overall survival in men with metastatic, castration-resistant prostate cancer (mCRPC), showing a 37% reduced risk of death compared to placebo, with median survival times of 18.4 months versus 13.6 months.

The results from the phase III AFFIRM trial support the continued targeting of the androgen receptor as an effective treatment strategy for prostate cancer, even after patients have developed resistance to castration therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide (formerly MDV3100) as a new therapeutic option for men with metastatic castration-resistant prostate cancer. Aragon-Ching, JB.[2021]

Enzalutamide, when combined with a Twist-targeting immunotherapy, significantly improved overall survival in a mouse model of castration-resistant prostate cancer (CRPC), extending survival from 10.3 weeks to 27.5 weeks.

The study found that enzalutamide did not impair the immune response generated by the Twist vaccine, suggesting that this combination therapy could be a safe and effective strategy for treating advanced-stage prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with a second-generation androgen receptor antagonist and a metastasis vaccine improves survival in a spontaneous prostate cancer model. Ardiani, A., Farsaci, B., Rogers, CJ., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05367440

NCT05367440 | Study of AZD5305 When Given in ... This study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of AZD5305 when given in combination with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.123

PETRANHA: Phase 1/2 study of AZD5305 + novel ... The PETRANHA study indicates that AZD5305 can be safely combined with three individual NHAs with low rates of dose interruptions or reductions.

3. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-prostate-cancer/164003-esmo-2025-first-interim-efficacy-analysis-of-the-phase-1-2-petranha-trial-of-saruparib-androgen-receptor-pathway-inhibitors-arpi-in-patients-pts-with-metastatic-prostate-cancer-mpc.html

ESMO 2025: First Interim Efficacy Analysis of the Phase 1/2 ... Saruparib (AZD5305) is a next-generation, PARP1-selective inhibitor with preclinical data indicating greater target engagement, efficacy, and safety compared ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9623235/

Preclinical Characterization of AZD5305, A Next- ... Overall, AZD5305 demonstrates that potent and selective inhibition and trapping of PARP1 represents a promising avenue to achieve improved outcomes for patients ...

5. genomemedicine.biomedcentral.com genomemedicine.biomedcentral.com/articles/10.1186/s13073-024-01370-z

The PARP1 selective inhibitor saruparib (AZD5305) elicits ... AZD5305 showed superior antitumor activity than the first-generation PARPi in terms of preclinical complete response rate (75% vs. 37%). The ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06120491

Study Details | NCT06120491 | Saruparib (AZD5305) vs ... The intention of the study is to demonstrate superiority of Saruparib (AZD5305) + physician's choice NHA relative to placebo + physician's choice NHA by ...

7. cancernetwork.com cancernetwork.com/view/saruparib-shows-favorable-activity-safety-in-mutant-advanced-solid-tumors

Saruparib Shows Favorable Activity, Safety in Mutant ... Saruparib at 20 mg once daily yielded a median best change in tumor size of –22.1% (range, –91.2% to 133.3%), an overall response rate (ORR) of ...

8. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9723C00001

Saruparib (AZD5305) vs Placebo in Men with Metastatic ... The intention of the study is to demonstrate superiority of Saruparib (AZD5305) + physician's choice NHA relative to placebo + physician's choice NHA.