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

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial tests whether the drug talazoparib, a type of targeted cancer therapy, either alone or combined with enzalutamide, a hormone therapy, can delay the progression of metastatic castration-resistant prostate cancer. This type of cancer continues to grow despite low testosterone levels in patients with specific gene mutations. The study targets individuals who have tried and not responded to abiraterone acetate, another prostate cancer treatment. Suitable candidates for the trial include those with metastatic castration-resistant prostate cancer who have identifiable mutations in certain genes, such as BRCA1 or BRCA2, and have experienced cancer progression. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

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

Research has shown that the combination of talazoparib and enzalutamide is generally manageable for people with metastatic castration-resistant prostate cancer (mCRPC). In studies, about 75% of patients paused their dose, and 56% reduced their dose of talazoparib due to side effects. However, these studies reported no treatment-related deaths.

The safety of talazoparib alone has also been studied. While effective, it can cause blood-related side effects. Talazoparib is being tested in this trial because earlier studies suggest it might be safe for patients, despite the possibility of some side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they offer new ways to tackle the disease. Unlike most treatments that focus solely on hormone therapy, talazoparib is a PARP inhibitor, which targets cancer cells by preventing them from repairing their DNA. When combined with enzalutamide, a standard anti-androgen therapy, it has the potential to enhance cancer-fighting effects. The standalone use of talazoparib at a higher dose also presents an alternative approach, possibly offering a more potent attack on cancer cells without the need for additional hormone therapy. These innovative strategies could lead to more effective treatments for prostate cancer, especially for those who have limited options.

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

This trial will compare the effects of using talazoparib with enzalutamide versus talazoparib alone for patients with metastatic castration-resistant prostate cancer (mCRPC) who have specific genetic changes known as HRR mutations. Studies have shown that combining talazoparib and enzalutamide can significantly benefit these patients, reducing the risk of cancer progression or death by 37% compared to using only enzalutamide. One study showed that 67% of patients responded positively to this combination, with about two-thirds experiencing a beneficial effect on their cancer. Meanwhile, talazoparib alone has shown promise, with patients experiencing 5.6 to 8.6 months where their cancer did not worsen. Overall, using these drugs together seems to provide a stronger benefit in slowing cancer progression. ^{3 6 7 8 9}

Who Is on the Research Team?

Alicia Morgans, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. dailynews.ascopubs.org dailynews.ascopubs.org/do/final-talapro-2-results-first-line-talazoparib-plus-enzalutamide-improves-survival

Final TALAPRO-2 Results: First-Line Talazoparib Plus ... Among the 805 unselected patients followed for a median of approximately 53 months, median OS reached 45.8 months with talazoparib plus ...

2. nature.com nature.com/articles/s41591-023-02704-x

First-line talazoparib with enzalutamide in HRR-deficient ... Confirmed objective response rate in patients with measurable disease at baseline was 67% (49/73; 95% CI, 55.1% to 77.7%) for the talazoparib ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12187471/

Talazoparib for prostate cancer and breast cancer - PMC After a median follow-up of 11.2 months, radiological progression-free survival was 8.6 months and 5.6 months, respectively. There was no ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S014067362500683X

Talazoparib plus enzalutamide in men with HRR-deficient ... Talazoparib plus enzalutamide resulted in statistically significant and clinically meaningful improvement in survival versus enzalutamide plus placebo, further ...

5. esmo.org esmo.org/oncology-news/combination-of-talazoparib-and-enzalutamide-prolongs-os-in-unselected-and-patients-with-hrr-deficient-mcrpc

A Combination of Talazoparib and Enzalutamide Prolongs ... The primary analysis of this phase III study combining talazoparib with enzalutamide demonstrated significantly improved radiographic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11954501/

Comparative efficacy and safety of talazoparib plus ... TALA + ENZA showed favorable results across multiple efficacy endpoints, but not across hematological toxicities compared with other 1L treatments.

7. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158225-asco-gu-2025-final-overall-survival-with-talazoparib-enzalutamide-as-first-line-treatment-in-patients-with-hrr-deficient-mcrpc-in-the-phase-3-talapro-2-trial.html

ASCO GU 2025: Final Overall Survival with Talazoparib ... The phase 3 TALAPRO-2 trial met its primary endpoint, showing improved radiographic progression-free survival for talazoparib + enzalutamide versus placebo + ...

8. ejcancer.com ejcancer.com/article/S0959-8049(24)01209-7/fulltext

Talazoparib plus enzalutamide in metastatic castration- ... There were no treatment-related deaths in the talazoparib plus enzalutamide group for either population. Serious TEAEs and deaths are summarized ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.5076

Clinical and safety outcomes of TALAPRO-2: A two-part ... PK data showed that ENZA increased TALA exposure and that TALA 0.5 mg QD + ENZA maintained similar TALA exposure to that achieved with 1 mg QD ...