Talazoparib for Breast Cancer

Recruiting at 7 trial locations

Overseen By Neelima Vidula, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: PARP inhibitors, P-glycoprotein inhibitors

Disqualifiers: Germline BRCA mutation, Active malignancy, 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: Unknown

Duration: Up to approximately 2 years

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Talazoparib, a medication that may treat metastatic breast cancer in individuals with specific BRCA 1 or BRCA 2 mutations. The main goal is to evaluate the medication's effectiveness for those with advanced breast cancer that has worsened after previous treatments. Suitable candidates have metastatic breast cancer with a specific BRCA mutation, identifiable through a blood test, and have experienced cancer progression after certain other treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial requires that you stop any anti-cancer therapy, including chemotherapy, hormone therapy, immunotherapy, or other investigational therapies, before joining. You should not be on strong P-glycoprotein inhibitors either. If you are taking any of these, you will need to stop them to participate.

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

Previous studies have shown that talazoparib has a specific safety profile. In a small number of patients, about 0.4% or 3 out of 788, serious bone marrow problems such as Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) have been reported. These issues are rare but important to note.

The FDA has approved talazoparib for treating certain breast cancers with BRCA mutations, which provides some reassurance about its safety. However, like all treatments, it may have side effects, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Talazoparib is unique because it targets breast cancer cells by inhibiting an enzyme called PARP (poly ADP-ribose polymerase). This mechanism disrupts the cancer cells' ability to repair their DNA, leading to cell death. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, Talazoparib's targeted approach aims to spare healthy cells, potentially reducing side effects. Researchers are excited about Talazoparib because it offers a more precise treatment option and could be particularly beneficial for patients with specific genetic mutations, such as BRCA mutations.

What evidence suggests that Talazoparib might be an effective treatment for metastatic breast cancer with a BRCA 1 or BRCA 2 mutation?

Research has shown that Talazoparib, the treatment under study in this trial, can help treat metastatic breast cancer in patients with BRCA 1 or BRCA 2 mutations. In earlier studies, 5.5% of patients experienced complete cancer remission, and 57.1% saw their cancer shrink. Another study found that Talazoparib outperformed standard treatments for these patients. In some trials, it achieved a 50% response rate, with 86% of patients experiencing positive effects. On average, patients lived 8.7 months without cancer progression. ^{6 7 8 9 10}

Who Is on the Research Team?

Neelima Vidula, M.D.

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with metastatic breast cancer that has a specific BRCA mutation detected in tumor DNA, not inherited. Participants must have progressed after prior treatments or be unsuitable for them, and should not be on certain drugs or have untreated brain metastases. They need functioning organs and controlled previous cancers, agree to contraception if applicable, and cannot be pregnant.

Inclusion Criteria

I finished my last breast cancer treatment at least two weeks ago and have recovered from side effects.

My cancer does not have a harmful BRCA 1 or 2 mutation.

My triple negative breast cancer has worsened after at least one chemotherapy treatment.

Exclusion Criteria

I am not taking strong P-glycoprotein inhibitors.

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 7 months after the last dose of trial treatment

I haven't had cancer treatment or recovered from its side effects in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Talazoparib capsules for oral administration daily

Up to approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Talazoparib

Trial Overview The trial tests Talazoparib's effectiveness against metastatic breast cancer with somatic BRCA mutations. It examines how well patients respond to this PARP inhibitor when they've had limited or no success with other therapies including platinum-based chemotherapy.

How Is the Trial Designed?

Group I: Talazoparib Experimental Treatment 1 Intervention

-Talazoparib will be provided as capsules for oral administration 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?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

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

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 the ABRAZO study, talazoparib (1 mg/day) maintained global health status and quality of life (GHS/QoL) in patients with advanced breast cancer, with median time to deterioration of GHS/QoL being 2.8 months for those with prior platinum therapy and 5.5 months for those with multiple cytotoxic regimens.

Patients reported significant improvements in breast and arm symptoms, as well as their future perspective, despite some deterioration in role functioning and dyspnoea symptoms, indicating that talazoparib can provide meaningful benefits in symptom management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with talazoparib after platinum or multiple cytotoxic non-platinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations: patient-reported outcomes from the ABRAZO phase 2 trial. Hurvitz, SA., Quek, RGW., Turner, NC., 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]

In a study involving 136 patients with gBRCA1/2 mutated HER2-positive advanced breast cancer, talazoparib did not show a significant improvement in disease-free survival (DFS) or overall survival (OS) compared to conventional chemotherapy after a median follow-up of 70.9 months.

The results suggest that talazoparib is not more effective than standard chemotherapy for this patient population, indicating that treatment decisions should consider this lack of difference in outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between talazoparib and conventional chemotherapy in the treatment of HER2-positive breast cancer patients: A retrospective study. Wang, N., Yu, X.[2022]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10649377/

final overall survival results from the EMBRACA trial - PMC In BRCA1/2-mutated advanced breast cancer, talazoparib did not significantly improve overall survival (OS) vs chemotherapy. OS results were ...

2. talzenna.pfizerpro.com talzenna.pfizerpro.com/efficacy-safety/efficacy

Efficacy | TALZENNA® (talazoparib) HCP Site | Safety Info Complete response —5.5% achieved a complete response with TALZENNA vs 0% with chemotherapy · Partial response —57.1% achieved a partial response with TALZENNA ...

3. nature.com nature.com/articles/s41598-024-64343-7

Cost-effectiveness of talazoparib for patients with germline ... According to the results of this trial, Talazoparib is more effective than standard treatment for patients with BRCA1/2 mutant advanced breast ...

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

Talazoparib in Patients with Advanced Breast Cancer and ... In a phase 1 trial, talazoparib monotherapy (at a dose of 1 mg once daily) resulted in a 50% response rate and an 86% clinical benefit rate at ...

5. academic.oup.com academic.oup.com/oncolo/article/28/5/414/7084883

Characteristics, Treatment, and Outcomes of Real-World ... Median time to talazoparib treatment failure was 8.5 months (95% CI, 8.0-9.7), median progression-free survival was 8.7 months (95% CI, 8.0-9.9) ...

6. talzenna.pfizerpro.com talzenna.pfizerpro.com/efficacy-safety/safety-profile

Safety Profile Overall, MDS/AML has been reported in 0.4% (3 out of 788) of solid tumor patients treated with TALZENNA as a single agent in clinical studies. In TALAPRO-2, MDS ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/211651s008lbl.pdf

Talzenna - accessdata.fda.gov TALZENNA is indicated for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated ( ...

8. talzenna.com talzenna.com/

Homepage | TALZENNA® (talazoparib) | Safety Info TALZENNA may cause serious side effects, including: Bone marrow problems called Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML). Some people who ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/talzenna-epar-product-information_en.pdf

Talzenna, INN-talazoparib - European Medicines Agency Breast cancer Patients should be selected for the treatment of breast cancer with Talzenna based on the presence of deleterious or suspected deleterious ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7066700/

Talazoparib in Patients with a Germline BRCA‐Mutated ... Talazoparib is a viable option for patients with germline BRCA‐mutated advanced breast cancer. This article presents detailed safety analyses for talazoparib, ...