Talazoparib + Tazemetostat for Prostate Cancer

Recruiting at 1 trial location

Overseen By Atish Choudhury, MD PhD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must be taking: LHRH or GnRH agonists

Must not be taking: P-gp inhibitors, CYP3A4 inducers

Disqualifiers: Brain metastases, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: 9

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether molecularly targeted oral medications called talazoparib and tazemetostat can be safely combined for the treatment of prostate cancer, and whether the combination is effective in shrinking or preventing the growth of metastatic prostate cancer. The names of the study drugs involved in this study are: * Talazoparib * Tazemetostat

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

The trial protocol does not specify if you must stop taking your current medications, but it does exclude participants taking certain medications that interact with the study drugs. You should discuss your current medications with the trial team to ensure there are no interactions.

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

Talazoparib has shown antitumor activity in men with metastatic castration-resistant prostate cancer, particularly in those with DNA damage response alterations. It is also approved for treating certain types of breast cancer, indicating its potential effectiveness in targeting cancer cells. ^{1 2 3 4 5}

What is known about the safety of Talazoparib for prostate cancer?

Talazoparib has shown antitumor activity with a manageable safety profile in men with metastatic castration-resistant prostate cancer, according to the TALAPRO-1 study. ^{1 2 3 5 6}

What makes the drug combination of Talazoparib and Tazemetostat unique for prostate cancer treatment?

The combination of Talazoparib and Tazemetostat is unique because Talazoparib is a PARP inhibitor that targets DNA repair mechanisms, showing promise in prostate cancer with specific genetic alterations, while Tazemetostat is an EZH2 inhibitor, potentially enhancing the treatment's effectiveness by targeting cancer cell growth pathways. ^{1 2 3 4 7}

Research Team

Atish D. Choudhury

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adult men with advanced prostate cancer that has spread and is worsening, despite previous hormone therapy. They must be able to swallow pills, have good organ function, agree to use contraception, and undergo a biopsy for genetic testing. Men with HIV or hepatitis can join if well-controlled. Excluded are those on certain other drugs, with recent thrombosis, uncontrolled illnesses, brain metastases or another active cancer.

Inclusion Criteria

I am mostly able to carry out my daily activities.

I have been treated with a PARP inhibitor before.

My heart function is classified as class 2B or better according to the NYHA.

Exclusion Criteria

I haven't had chemotherapy, experimental treatments, or radiotherapy in the last 4 weeks.

I haven't taken any cancer pills like hormone therapy or experimental drugs in the last 14 days.

I do not have brain metastases or leptomeningeal disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

Participants receive talazoparib and tazemetostat at a dose of 75% of the starting dose for their FDA-approved indications to find a safe dose

28 days per cycle

4 visits (in-person) per cycle

Dose Expansion

Participants receive talazoparib and tazemetostat at the safe dose identified in the dose escalation phase

28 days per cycle

4 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 24 months

Periodic visits (in-person)

Treatment Details

Interventions

• Talazoparib
• Tazemetostat

Trial Overview The trial tests combining talazoparib and tazemetostat—oral medications targeting specific molecular pathways in prostate cancer cells—to see if they're safe together and effective against metastatic prostate cancer.

Participant Groups

Group I: Dose Expansion Talazoparib + Tazemetostat Experimental Treatment 2 Interventions

Participants will receive talazoparib and tazemetostat at the safe dose identified in the first part (dose escalation) of the study. During each 28 day study treatment cycle participants will take: * Talazoparib once daily. * Tazemetostat twice daily.

Group II: Dose Escalation Talazoparib + Tazemetostat Experimental Treatment 2 Interventions

Standard 3+3 dose escalation will be followed, participants will initially receive talazoparib and tazemetostat at a dose of 75% of the starting dose for their FDA-approved indications. During each 28 day study treatment cycle participants will take: * Talazoparib once daily. * Tazemetostat twice daily.

Talazoparib is already approved in United States, European Union for the following indications:

Approved in United States as Talzenna for:

• Deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer

Approved in European Union as Talzenna for:

• Monotherapy for the treatment of adult patients with germline BRCA1/2 mutations, who have HER2-negative locally advanced or metastatic breast cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Epizyme, Inc.

Industry Sponsor

Trials

34

Recruited

2,800+

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

Findings from Research

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]

Talazoparib is an oral PARP inhibitor recently approved in the USA for treating adults with specific types of breast cancer, particularly those with BRCA mutations, highlighting its targeted efficacy in a defined patient population.

The drug is also being explored for use in other cancers, including metastatic castration-resistant prostate cancer and early triple negative breast cancer, indicating its potential versatility in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib: First Global Approval. Hoy, SM.[2020]

A phase I trial involving 41 pediatric patients with recurrent or refractory solid tumors showed that the combination of talazoparib and irinotecan, with or without temozolomide, is feasible and has demonstrated activity, particularly in Ewing sarcoma, with objective response rates of 10.3% for arm A and 25% for arm B.

The most common severe side effects included neutropenia and thrombocytopenia, indicating that while the treatment is active, it also carries significant hematologic risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies. Federico, SM., Pappo, AS., Sahr, N., et al.[2021]

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-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 a real-world study of 84 patients with germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer, talazoparib showed a median progression-free survival of 8.7 months and an overall response rate of 63.1%, indicating its efficacy in this population.

The study found that factors such as brain metastasis and a poor performance status (ECOG PS ≥2) at the start of talazoparib treatment were linked to worse outcomes, highlighting the importance of patient characteristics in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics, Treatment, and Outcomes of Real-World Talazoparib-Treated Patients With Germline BRCA-Mutated Advanced HER2-Negative Breast Cancer. Savill, KMZ., Ivanova, J., Asgarisabet, P., et al.[2023]

References

1. 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]

2. 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]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Talazoparib: First Global Approval. [2020]

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

A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies. [2021]

5. 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]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Characteristics, Treatment, and Outcomes of Real-World Talazoparib-Treated Patients With Germline BRCA-Mutated Advanced HER2-Negative Breast Cancer. [2023]