Talazoparib ± Enzalutamide for Prostate Cancer

(TALENT Trial)

Recruiting at 1 trial location

Overseen By Sarah Wise

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Prostate Cancer Clinical Trials Consortium

Must be taking: Gonadotropin-releasing hormone

Must not be taking: P-gp inhibitors, CYP2C8 inhibitors

Disqualifiers: Active malignancy, Seizure history, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 42 months

126 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether talazoparib in combination with enzalutamide or talazoparib alone delays cancer progression in people with metastatic castration-resistant prostate cancer (mCRPC) who have homologous recombination repair (HRR) mutations and have previously received abiraterone acetate.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participation. You must not use potent P-gp inhibitors, strong CYP2C8 inhibitors, strong CYP3A4 inducers, or certain hormonal agents within specified periods before starting the study. Check with the trial team to see if your current medications are on the list.

What data supports the effectiveness of the drug combination Talazoparib and Enzalutamide for prostate cancer?

Research shows that Talazoparib, when used with Enzalutamide, has potential benefits for men with metastatic castration-resistant prostate cancer, especially those with specific genetic changes related to DNA repair. This combination has shown promise in improving the time patients live without their cancer getting worse. ^{1 2 3 4 5}

Is Talazoparib plus Enzalutamide safe for humans?

Talazoparib has shown a manageable safety profile in men with metastatic castration-resistant prostate cancer, and studies are ongoing to evaluate the safety of combining it with Enzalutamide. ^{1 2 4 5 6}

How is the drug Talazoparib different from other prostate cancer treatments?

Talazoparib is unique because it is a PARP inhibitor that targets cancer cells with specific DNA repair gene alterations, and when combined with enzalutamide, it may enhance treatment effectiveness for prostate cancer that has spread and is resistant to standard hormone therapy. ^{1 2 3 4 5}

Research Team

Alicia Morgans, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Men over 18 with advanced prostate cancer that's resistant to castration and has specific genetic mutations. They must have had prior treatment with abiraterone, be able to swallow pills, have good performance status (ECOG ≤1), normal organ function, and agree to contraception. Excluded are those with allergies to the drugs tested, other active cancers needing treatment within 3 years, seizure history or risks, certain medical conditions or treatments that could interfere.

Inclusion Criteria

I can swallow pills whole.

I am fully active and can carry on all pre-disease activities without restriction.

Willing and able to provide, or have a legally authorized representative provide, written informed consent and privacy authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. Privacy authorization may be either included in the informed consent or obtained separately.

Exclusion Criteria

Known allergy to any of the compounds under investigation.

I don't have any other active cancers or any diagnosed in the last 3 years needing treatment.

Use of investigational agents for the treatment of prostate cancer within 4 weeks of the start of study treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talazoparib with or without enzalutamide in continuous 28-day cycles

42 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Enzalutamide
• Talazoparib

Trial Overview The trial is testing whether talazoparib alone or combined with enzalutamide can slow down cancer growth in men whose prostate cancer has spread and is not responding to hormone therapy anymore. These patients also have genetic changes making their cancer potentially more sensitive to these drugs.

Participant Groups

Group I: Arm B Experimental Treatment 1 Intervention

Talazoparib (1 mg PO QD) will be administered in continuous 28-day cycles.

Group II: Arm A Active Control 1 Intervention

Talazoparib (0.5 mg PO QD) and enzalutamide (160 mg PO QD) will be administered in continuous 28-day cycles.

Who Is Running the Clinical Trial?

Prostate Cancer Clinical Trials Consortium

Lead Sponsor

Trials

12

Recruited

7,400+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Findings from Research

In the TALAPRO-1 study involving 97 men with metastatic castration-resistant prostate cancer (mCRPC), talazoparib significantly improved health-related quality of life (HRQoL) and reduced pain levels, particularly in patients with BRCA1/2 mutations.

The study found that 84% of all patients and 83% of those with BRCA1/2 mutations did not experience a deterioration in worst pain after 12 months of treatment, indicating a high probability of maintaining pain relief while receiving talazoparib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1. Saad, F., de Bono, J., Barthélémy, P., et al.[2023]

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 TALAPRO-2 trial is an ongoing study involving 1037 men with metastatic castration-resistant prostate cancer, testing the combination of talazoparib and enzalutamide to see if it improves survival without cancer progression compared to enzalutamide plus a placebo.

This trial aims to assess not only the efficacy of the drug combination but also the side effects experienced by participants, while also analyzing tumor DNA for faulty repair genes, which could provide insights into treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary of the design of the TALAPRO-2 study comparing talazoparib and enzalutamide versus enzalutamide and placebo in men with metastatic castration-resistant prostate cancer. Agarwal, N., Azad, A., Shore, ND., 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 the phase II TALAPRO-1 study involving 127 men with metastatic castration-resistant prostate cancer, talazoparib demonstrated a manageable safety profile, with 95.3% of participants experiencing treatment-emergent adverse events, primarily mild to moderate in severity.

The most common adverse events included anemia (48.8%), nausea (33.1%), and decreased appetite (28.3%), but serious complications were rare, with no grade 5 events or treatment-related deaths, indicating that talazoparib can be safely administered with appropriate monitoring and supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses. Mehra, N., Fizazi, K., de Bono, JS., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1. [2023]

2. England pubmed.ncbi.nlm.nih.gov

TALAPRO-3 clinical trial protocol: phase III study of talazoparib plus enzalutamide in metastatic castration-sensitive prostate cancer. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Plain language summary of the design of the TALAPRO-2 study comparing talazoparib and enzalutamide versus enzalutamide and placebo in men with metastatic castration-resistant prostate cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: TALAPRO-2 phase III study design. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses. [2023]