Talazoparib for Advanced Cancer with BRCA Gene Alterations

Overseen By Sarina Piha-Paul, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: PARP inhibitors

Disqualifiers: Pregnancy, HIV, Hepatitis, CNS metastases, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: Up to 1 year

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be at least 4 weeks beyond any chemotherapy or investigational therapy, or at least 5 half-lives from hormonal, biological, or targeted agents before starting the trial.

What data supports the effectiveness of the drug Talazoparib for advanced cancer with BRCA gene alterations?

Talazoparib has shown effectiveness in treating advanced breast cancer in patients with BRCA gene mutations, where it improved survival and quality of life compared to chemotherapy. It works by blocking a protein that helps repair damaged DNA in cancer cells, making it harder for them to survive. ^{1 2 3 4 5}

Is Talazoparib safe for humans?

Talazoparib has been approved by the FDA and EMA for treating certain types of breast cancer, indicating it has been evaluated for safety. Clinical studies have shown it to be generally safe, but like all medications, it may have side effects, which should be discussed with a healthcare provider. ^{2 3 4 5 6}

How is the drug Talazoparib unique for treating advanced cancer with BRCA gene alterations?

Talazoparib is unique because it is an oral drug that specifically targets and inhibits PARP enzymes, which are crucial for repairing DNA damage in cancer cells with BRCA mutations. This mechanism, known as synthetic lethality, makes it more effective than traditional chemotherapy for certain patients, improving outcomes like progression-free survival and quality of life. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II trial studies how well talazoparib works in treating patients with cancers that have returned after a period of improvement, do not respond to treatment, or have spread to other parts of the body, and have alterations in the breast cancer, early onset (BRCA) genes. Talazoparib may cause tumor cells to die by blocking an enzyme that protects the tumor cells from damage.

Research Team

Sarina Piha-Paul, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with advanced or metastatic cancers that are resistant to standard therapy, have relapsed, and have BRCA gene alterations. They must not be pregnant or breastfeeding, should not have active infections requiring IV antibiotics, and cannot have brain metastases unless stable. Participants need normal blood counts and organ function tests, can't be on recent cancer treatments, must agree to use contraception if applicable.

Inclusion Criteria

Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Time requirements since last treatment

Specific blood count requirements (Absolute neutrophil count, Platelets, Hemoglobin)

Exclusion Criteria

Inability to comply with study procedures

I have not had a stroke, heart attack, or severe chest pain recently.

Psychiatric or substance abuse disorders interfering with trial cooperation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talazoparib orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Follow-up at 30 days and then every 12 weeks

Treatment Details

Interventions

• Talazoparib

Trial Overview The study is testing Talazoparib's effectiveness in treating various recurrent or refractory cancers with BRCA gene changes. It examines how well this drug causes cancer cells to die by blocking a specific enzyme they need to repair themselves.

Participant Groups

Group I: Treatment (talazoparib) Experimental Treatment 3 Interventions

Patients receive talazoparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase III trial, talazoparib, a PARP inhibitor, showed promising results for patients with advanced or metastatic HER2-negative breast cancer and BRCA1/2 mutations, leading to some complete responses and prolonged progression-free survival.

Patients treated with talazoparib also experienced improved overall quality of life compared to those receiving chemotherapy, highlighting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib Bests Chemo for Breast Cancer. [2019]

Talazoparib tosylate is an FDA and EMA-approved oral PARP inhibitor specifically effective for treating breast cancer in patients with germline BRCA mutations, showing superior efficacy compared to other PARP inhibitors and standard chemotherapy.

The drug works through a mechanism called synthetic lethality, which means it targets cancer cells' weaknesses, providing significant clinical benefits for patients with advanced or metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib to treat BRCA-positive breast cancer. Guney Eskiler, G.[2019]

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]

In a study of 20 patients with operable BRCA-positive breast cancer, talazoparib treatment for 6 months resulted in a 53% rate of complete pathologic response (RCB-0) and a 63% rate of minimal residual disease (RCB-0/I), indicating significant efficacy without chemotherapy.

While talazoparib was effective, it also caused manageable side effects, with 40% of patients experiencing grade 3 anemia and requiring transfusions, highlighting the importance of monitoring and managing toxicity during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. Litton, JK., Scoggins, ME., Hess, KR., et al.[2021]

Talazoparib showed promising antitumor activity in patients with advanced breast cancer who have germline BRCA1/2 mutations, achieving a confirmed objective response rate of 21% in those with a recent response to platinum therapy and 37% in those with multiple prior treatments.

The most common side effects were manageable, with anemia occurring in 52% of patients, and only 4% of patients discontinued the drug due to adverse events, indicating a relatively safe profile for talazoparib in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Turner, NC., Telli, ML., Rugo, HS., et al.[2021]

Talazoparib, a PARP inhibitor, has been approved for treating metastatic breast cancer in patients with germline BRCA1/2 mutations, showing superior progression-free survival compared to standard chemotherapy in a phase III trial.

The review discusses talazoparib's safety profile and explores its potential effectiveness when combined with standard cytotoxic drugs and novel therapies, highlighting its role in enhancing treatment options for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence to date: talazoparib in the treatment of breast cancer. Exman, P., Barroso-Sousa, R., Tolaney, SM.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Talazoparib Bests Chemo for Breast Cancer. [2019]

2. Spain pubmed.ncbi.nlm.nih.gov

Talazoparib to treat BRCA-positive breast cancer. [2019]

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

Talazoparib: First Global Approval. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). [2021]

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

Evidence to date: talazoparib in the treatment of breast cancer. [2020]