Talazoparib + Enzalutamide for Prostate Cancer

Overseen By Amado Zurita-Saavedra, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Androgen ablation therapy

Must not be taking: Estrogens, Glucocorticoids

Disqualifiers: Small cell histology, Bone metastasis, Chemotherapy, Seizures, Hypertension, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well adding talazoparib, a new drug, works with standard prostate cancer treatments like hormone therapy and enzalutamide (also known as Xtandi) for patients whose cancer has spread to the lymph nodes. The researchers aim to determine if this combination can better manage the cancer before surgery. It suits those with prostate cancer that has spread to the lymph nodes and who plan to undergo surgery after treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that medications known to lower the seizure threshold be discontinued or substituted at least 4 weeks before starting the study. Additionally, treatment with estrogens, cyproterone acetate, or glucocorticoids at a dose greater than 10 mg/day of prednisone equivalent must be stopped 4 weeks prior to the study.

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

Research has shown that combining talazoparib with enzalutamide extends the lives of patients with metastatic prostate cancer, indicating that the two drugs work effectively together. Understanding their safety is also crucial.

Studies have found that most patients tolerate this drug combination well. While some experienced side effects, common in cancer treatments, these were manageable. No new safety concerns emerged, making the combination safe enough for further clinical trials.

Prospective trial participants should discuss potential side effects with their doctor, who can provide information tailored to their health. Overall, research supports the safety of using these drugs together for advanced prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about combining Talazoparib with Enzalutamide for prostate cancer because this combination could offer a more powerful way to tackle the disease. Most treatments for prostate cancer, like Enzalutamide alone, focus on blocking hormones that fuel cancer growth. However, Talazoparib brings a fresh approach by targeting and interfering with cancer cells' DNA repair process, potentially making the cells more vulnerable to treatment. This dual-action strategy might enhance the effectiveness of existing therapies, offering a new hope for patients.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Research has shown that combining talazoparib with enzalutamide can extend the lives of men with prostate cancer. Studies have found that this combination increases progression-free survival, the time patients live without their cancer worsening. In one study, patients taking both talazoparib and enzalutamide lived an average of 42.4 months, compared to 32.6 months for those not taking talazoparib. This combination is particularly beneficial for patients without certain genetic changes, such as BRCA1/2 mutations. Overall, evidence suggests that talazoparib with enzalutamide is more effective than enzalutamide alone for treating advanced prostate cancer. Participants in this trial will receive ADT plus enzalutamide for 8 weeks, followed by the addition of talazoparib. ^{1 3 6 7 8}

Who Is on the Research Team?

Amado Zurita-Saavedra, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Men with prostate cancer that has spread to lymph nodes can join this trial if they're in good enough health for surgery, have not had certain other treatments or conditions, and agree to use contraception. They must also be willing to provide tissue samples and follow the study's procedures.

Inclusion Criteria

I am considered fit for surgery and plan to have a radical prostatectomy after pre-surgery treatment.

I've had hormone therapy for up to 6 weeks and can provide a tumor sample from before starting it.

Patients must agree to tissue collection for correlative studies at the specified timepoints. At the study entry, any previously collected diagnostic tumor biopsy blocks from primary and/or metastatic tissues must be provided.

Exclusion Criteria

My cancer has spread to my bones or other areas beyond the original site.

My cancer is confirmed to be small cell or sarcomatoid through a biopsy.

Planned participation in any other experimental drug study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ADT plus Enzalutamide for 8 weeks, followed by Talazoparib

8 weeks

Surgery

Participants undergo surgical consolidation after treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including 1-year PSA levels and 5-year survival outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Talazoparib

Trial Overview The trial is testing how well talazoparib works when added to standard hormone therapy (ADT) and enzalutamide before surgery in men with prostate cancer. It aims to see if this combination helps reduce the cancer more effectively.

How Is the Trial Designed?

Group I: ADT plus Enzalutamide plus Talazoparib Experimental Treatment 5 Interventions

Participant will recive ADT plus Enzalutamide for a total of 8 weeks. After about 8 weeks of ADT and Enzalutamide treatment, participant will begin taking Talazoparib

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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]

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]

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]

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 the PREVAIL trial, enzalutamide significantly improved both radiographic progression-free survival and overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (CRPC), demonstrating its efficacy as a treatment option.

Enzalutamide was well tolerated and delayed the need for chemotherapy and decline in health-related quality of life, making it a convenient choice for patients who are asymptomatic or mildly symptomatic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer. Keating, GM.[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]

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]

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]

Citations

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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. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)00683-X/abstract

Talazoparib plus enzalutamide in men with HRR-deficient ... In patients without BRCA1/2 alterations (n=244 [61%]), median overall survival was 42·4 months for talazoparib plus enzalutamide versus 32·6 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.11120

Results from the phase 3 TALAPRO-2 study. TALAPRO-2 demonstrated statistically significant improvement with TALA + ENZA vs PBO + ENZA in radiographic progression-free survival.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40179906/?utm_source=FeedFetcher&utm_medium=rss&utm_campaign=None&utm_content=0Z5wLNSzd7Zm8l157G81VmL0kQLTE1edebsDTCoPVyF&fc=None&ff=20250404034840&v=2.18.0.post9+e462414

First-line talazoparib plus enzalutamide versus placebo ... First-line talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide in men with ...

5. facingourrisk.org facingourrisk.org/XRAY/Talzenna-for-metastatic-prostate-cancer-and-HRR-mutations

People with metastatic castration-resistant prostate cancer. Participants treated with Talzenna and Xtandi survived an average of 45 months from the start of treatment. · Participants treated with placebo ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40683290/

Talazoparib plus enzalutamide in men with metastatic ... Combining talazoparib with enzalutamide significantly improved overall survival in patients with metastatic castration-resistant prostate cancer.

7. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158136-asco-gu-2025-final-overall-survival-with-talazoparib-enzalutamide-as-first-line-treatment-in-unselected-patients-with-mcrpc-in-the-phase-3-talapro-2-trial.html

ASCO GU 2025: Final Overall Survival with Talazoparib ... The median radiographic progression free survival in the talazoparib group was 33.1 months, which was 13.6 months longer than the active control ...

8. talzennaxtandi.pfizerpro.com talzennaxtandi.pfizerpro.com/efficacy/os

OS TALZENNA + XTANDI demonstrated a statistically significant improvement in overall survival vs XTANDI + placebo 1. 14-month difference in median overall ...