Talazoparib + Enzalutamide for Prostate Cancer

(TALAPRO-2 Trial)

Not currently recruiting at 473 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must not be taking: Opioids, P-gp inhibitors

Disqualifiers: Cardiovascular disease, Renal dysfunction, Hepatic dysfunction, Brain metastasis, 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

Duration: Up to 42 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for prostate cancer that has spread and resists standard hormone therapy. It tests whether adding talazoparib, a PARP inhibitor, to enzalutamide (Xtandi) delays cancer progression more effectively than enzalutamide alone. Men with metastatic castration-resistant prostate cancer (mCRPC) whose disease has worsened despite current treatments might be suitable candidates. Participants should have cancer that has spread to bones or soft tissues and should not have received certain other prostate cancer treatments before. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use potent P-gp inhibitors within 7 days before starting the trial. 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?

Research has shown that using talazoparib and enzalutamide together is generally safe for patients with advanced prostate cancer that no longer responds to hormone therapy. Previous studies found that this combination has a manageable safety profile, with serious side effects being uncommon.

Enzalutamide alone is an approved treatment for prostate cancer, and doctors are familiar with its side effects and management.

Overall, evidence suggests that both the combination and enzalutamide alone are safe, with usually manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Talazoparib and Enzalutamide for prostate cancer because it offers a unique approach compared to standard treatments like hormone therapies and chemotherapy. Talazoparib is a PARP inhibitor, which means it works by blocking a protein that cancer cells need to repair their DNA, potentially leading to their death. Enzalutamide, on the other hand, is an androgen receptor inhibitor that helps stop the growth of prostate cancer by blocking the effects of male hormones. This combination targets cancer cells in multiple ways, which could enhance its effectiveness against prostate cancer, especially for cases that haven't responded well to existing therapies.

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

Research has shown that combining talazoparib with enzalutamide, which participants in this trial may receive in the combination arm, may effectively treat advanced prostate cancer that no longer responds to hormone therapy. Specifically, studies demonstrated that this combination helped patients live an average of 45.8 months, compared to 37 months for those taking only enzalutamide, the treatment in the monotherapy arm of this trial. Patients on the combination treatment lived about 8.8 months longer on average. The results were statistically significant, indicating that this combination can extend life for people with this type of prostate cancer. These findings strongly suggest that the combination treatment could be more effective than enzalutamide alone. ^{1 6 7 8 9}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that's resistant to hormone therapy (mCRPC), not severely symptomatic, and have a life expectancy of at least 12 months. Participants must have rising PSA levels, be able to swallow pills, consent to genetic testing, and use effective contraception. Excluded are those who've had seizures, significant heart disease, recent opioid treatment for cancer pain or certain prior cancer treatments.

Inclusion Criteria

I have undergone treatment to lower my testosterone levels below 50 ng/dL.

Agree to specific contraception measures during and after the study treatment

Life expectancy ≥ 12 months as assessed by the investigator

Exclusion Criteria

I have a serious heart condition.

I have started treatment for prostate cancer before it spread.

My cancer spread is limited to lymph nodes below where my aorta splits.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety and PK Run-in

Open-label, non-randomized study to confirm the starting dose of talazoparib in combination with enzalutamide through assessment of target safety events and pharmacokinetics

66 days

Treatment

Randomized, double-blind, placebo-controlled study comparing talazoparib plus enzalutamide vs. placebo plus enzalutamide

Up to 42 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after the last dose

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Talazoparib

Trial Overview

The trial is examining if adding Talazoparib (a PARP inhibitor) to Enzalutamide (an anti-androgen drug) improves outcomes compared to using Enzalutamide alone in men with mCRPC. The study measures how long patients live without the disease getting worse.

How Is the Trial Designed?

Group I: Combination arm Experimental Treatment 1 Intervention

Talazoparib plus enzalutamide

Group II: Monotherapy arm Active Control 1 Intervention

Ezalutamide plus placebo

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

Enzalutamide (XTANDI) is an FDA-approved treatment for castration-resistant prostate cancer (CRPC) that effectively targets androgen receptor signaling, which is crucial for cancer progression.

In a Phase III clinical trial involving men with CRPC after chemotherapy, enzalutamide was well tolerated and significantly improved overall survival by 4.8 months, as indicated by reduced serum prostate-specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. Dhingra, R., Sharma, T., Singh, S., et al.[2021]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[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]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

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 a phase 2 study involving 60 patients with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide treatment led to a significant decline in prostate-specific antigen (PSA) levels in 45% of patients, indicating its efficacy in managing this advanced cancer.

The study found that the presence of the androgen receptor variant ARV7 was linked to primary resistance to enzalutamide, suggesting that certain androgen signaling characteristics before treatment can predict patient response to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Efstathiou, E., Titus, M., Wen, S., 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]

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 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]

In a study of 14 Japanese patients with castration-resistant prostate cancer (CRPC), enzalutamide (ENZ) demonstrated a high efficacy, with 92% of patients achieving a significant reduction in prostate-specific antigen (PSA) levels of 50% or more from baseline.

The safety profile of ENZ was favorable, with only mild adverse events occurring in more than 20% of patients, indicating that even reduced doses of ENZ (80 or 120 mg/day) are effective and safe for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Enzalutamide in a Real-World Cohort of Japanese Patients With Castration-resistant Prostate Cancer. Hori, A., Sahashi, H., Sano, S., et al.[2021]

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The phase 3 TALAPRO-2 trial met its primary endpoint, showing improved radiographic progression free survival for talazoparib + enzalutamide versus placebo + ...

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No significant safety issues occurred when participants took talazoparib. TALAPRO-2 results. Early TALAPRO-2 results were reported in February of 2023.