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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of talazoparib (Talzenna) for individuals with advanced cancers that have recurred, stopped responding to treatment, or spread, particularly when BRCA gene changes are present. Talazoparib targets cancer cells by preventing their repair. It suits those with specific genetic changes in the BRCA pathway whose cancer has progressed despite standard treatments. The study aims to determine if talazoparib can effectively slow or shrink these difficult-to-treat cancers. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that talazoparib is likely to be safe for humans?

Research has shown that talazoparib is generally safe. In studies involving individuals with advanced breast cancer and BRCA gene mutations, talazoparib reduced tumor size. The treatment also benefited those with advanced prostate cancer. Some side effects, such as nausea and tiredness, were reported, but most were manageable with standard care. Since talazoparib is in a Phase 2 trial, it has demonstrated sufficient safety to progress from earlier testing. This provides reasonable confidence in its safety for patients with BRCA gene changes. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Talazoparib is unique because it specifically targets cancer cells with BRCA gene alterations by inhibiting the PARP enzyme, which is crucial for DNA repair in these cells. While traditional treatments for advanced cancer often include chemotherapy, which attacks rapidly dividing cells indiscriminately, talazoparib offers a more targeted approach. This specificity not only promises to be more effective against tumors with BRCA mutations but also may result in fewer side effects, making it an exciting option for patients and researchers alike.

What evidence suggests that talazoparib might be an effective treatment for advanced cancer with BRCA gene alterations?

Research has shown that talazoparib, which participants in this trial will receive, works well for individuals with certain genetic changes, such as BRCA1 or BRCA2. For those with advanced breast cancer, talazoparib significantly delayed cancer progression. In studies involving prostate cancer patients, talazoparib extended the time they lived without their cancer worsening. These findings suggest that talazoparib could be promising for treating advanced cancers with BRCA gene changes. ^{1 2 3 4 5}

Who Is on the Research Team?

Sarina Piha-Paul, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11291882/

Phase II study of talazoparib in advanced cancers with BRCA1 ... Analyzing the outcomes across various cohorts treated with talazoparib, we observed a disparity in the trend of OS and PFS emerging when ...

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

People with metastatic castration-resistant prostate cancer. Talzenna appears to be most effective for people with BRCA1 or BRCA2 mutations but is also effective for people with certain other mutations.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1802905

Talazoparib in Patients with Advanced Breast Cancer and ... Patient-reported outcomes favored talazoparib; significant overall improvements and significant delays in the time to clinically meaningful ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02286687?locStr=United+States&country=United+States&aggFilters=status%3A

Study Details | NCT02286687 | Talazoparib in Treating ... This phase II trial studies how well talazoparib works in treating patients with cancers that have returned after a period of improvement, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12187471/

Talazoparib for prostate cancer and breast cancer - PMC After a median follow-up of 11.2 months, radiological progression-free survival was 8.6 months and 5.6 months, respectively. There was no ...