Talazoparib + Enzalutamide for Metastatic Prostate Cancer

Not currently recruiting at 446 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: GnRH agonists/antagonists

Must not be taking: Potent P-gp inhibitors

Disqualifiers: Seizure history, Brain metastasis, Cardiovascular disease, others

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

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two drugs, talazoparib (a PARP inhibitor) and enzalutamide (an androgen receptor inhibitor), to treat metastatic prostate cancer in men with a specific genetic feature (DDR-deficient). One group will receive both drugs, while another will receive a placebo plus enzalutamide. Men with prostate cancer that has spread and who have not received certain chemotherapy drugs may be suitable candidates. The trial aims to determine if the drug combination works better than enzalutamide alone. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, ongoing ADT (androgen deprivation therapy) with a GnRH agonist or antagonist must continue throughout the study. It's best to discuss your specific medications with the study team.

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

Research shows that combining talazoparib with enzalutamide may help treat prostate cancer. Studies have found that this combination can extend patients' lives compared to using enzalutamide alone, indicating its effectiveness in managing the disease.

Regarding safety, previous studies indicate that most patients tolerate the combination well. Some side effects occur, but they are usually manageable. Talazoparib is already FDA-approved for other uses, so its safety profile is well-understood.

Overall, while the treatment remains under study, current evidence suggests it is relatively safe. Prospective trial participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Talazoparib and Enzalutamide for metastatic prostate cancer because it offers a novel approach compared to current treatments. Most standard treatments target androgen receptors to slow cancer growth, but Talazoparib works differently by inhibiting PARP (poly ADP-ribose polymerase), an enzyme that helps repair DNA damage in cancer cells. This dual mechanism can potentially enhance cancer cell death and improve outcomes. Additionally, combining Talazoparib with Enzalutamide may offer a more effective treatment strategy by attacking the cancer on multiple fronts, which is an exciting development in the fight against metastatic prostate cancer.

What evidence suggests that talazoparib plus enzalutamide could be an effective treatment for metastatic prostate cancer?

Research has shown that using talazoparib with enzalutamide holds promise for treating advanced prostate cancer, particularly in patients with certain DNA repair issues. In this trial, one group will receive the combination of talazoparib and enzalutamide. Previous studies have demonstrated that this combination helped patients live about 14 months longer on average compared to those taking enzalutamide with a placebo. In another study, the average survival time was 45.8 months with the combination treatment, compared to 37 months for those not receiving it. Additionally, patients with specific DNA repair gene mutations experienced a longer time before the cancer worsened, lasting up to 28 months. These findings suggest that talazoparib plus enzalutamide can be more effective than enzalutamide alone. ^{1 2 3 4 5}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

Men 18+ (varies by country) with metastatic prostate cancer and confirmed DDR gene mutation. They must have adequate organ function, no prior docetaxel treatment for mCSPC, and agree to contraception use. Exclusions include previous treatments with certain drugs, active COVID-19 infection, history of seizures or major surgery within the last month.

Inclusion Criteria

I have not been treated with docetaxel for my prostate cancer.

I am willing and able to follow all study requirements.

My organs are functioning well enough for treatment.

Exclusion Criteria

I have a history of MDS, AML, or another cancer, with some exceptions.

You have not participated in any experimental medical treatments for at least four weeks before the study.

I have a serious heart condition.

Timeline for a Trial Participant

Prescreening

Initial assessment to determine potential eligibility for the trial

2-4 weeks

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either talazoparib with enzalutamide or placebo with enzalutamide

Up to 3 years

Safety Follow-up

Participants are monitored for safety after treatment

4 weeks

Long-term Follow-up

Participants are monitored for long-term outcomes and survival

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Talazoparib

Trial Overview The trial is testing the effectiveness of talazoparib combined with enzalutamide versus a placebo plus enzalutamide in men with DDR-deficient metastatic prostate cancer. The goal is to see if talazoparib can improve outcomes when added to standard therapy.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 1 Intervention

Talazoparib plus enzalutamide

Group II: Arm 2 Active Control 1 Intervention

Placebo plus enzalutamide

Enzalutamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

Pfizer

Lead 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

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Published Research Related to This Trial

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]

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]

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[2020]

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-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 ENZAMET phase III trial demonstrated that adding enzalutamide to standard treatment significantly prolongs survival in men with metastatic hormone-sensitive prostate cancer.

Enzalutamide is more effective than older nonsteroidal antiandrogen drugs, highlighting its potential as a superior treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide Bests Older NSAAs in mHSPC. [2021]

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. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizers-talzennar-combination-xtandir-improves-survival

Pfizer's TALZENNA® in Combination with XTANDI® ... TALZENNA + XTANDI is the first PARP inhibitor plus ARPI combination to demonstrate statistically significant and clinically meaningful ...

2. talzennaxtandi.pfizerpro.com talzennaxtandi.pfizerpro.com/efficacy/os

OS | TALZENNA® (talazoparib) + XTANDI® (enzalutamide) TALZENNA + XTANDI demonstrated a statistically significant improvement in overall survival vs XTANDI + placebo · 14-month difference in median overall survival ...

3. 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 ... The final results showed that median overall survival (OS) with talazoparib plus enzalutamide was improved in an unselected or all-comer mCRPC ...

4. targetedonc.com targetedonc.com/view/final-analysis-of-talapro-2-in-mcrpc-confirms-significant-benefit

Final Analysis of TALAPRO-2 in mCRPC Confirms ... The combination therapy demonstrated a median overall survival of 45.8 months versus 37.0 months for the control group, with a hazard ratio of ...

5. facingourrisk.org facingourrisk.org/XRAY/talazoparib-for-metastatic-prostate-cancer

Early data shows talazoparib improves prostate cancer ... Among participants with inherited or tumor mutations in a DNA repair gene, progression-free survival was 28 months for those who received Talzenna plus Xtandi ...