Talazoparib for Breast Cancer

Recruiting at 6 trial locations

Overseen By Neelima Vidula, M.D.

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Massachusetts General Hospital

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

Disqualifiers: Germline BRCA mutation, Active malignancy, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing talazoparib, a drug that may help treat breast cancer that has spread and has specific genetic mutations (BRCA 1 or BRCA 2). Talazoparib works by stopping proteins that repair DNA, making it harder for cancer cells to survive. The goal is to see if this drug can reduce tumor size and slow down cancer growth in these patients. Talazoparib is a new treatment recently approved for use in patients with metastatic breast cancer with germline BRCA mutations.

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.

What data supports the effectiveness of the drug Talazoparib for breast cancer?

Talazoparib has shown effectiveness in patients with advanced or metastatic HER2-negative breast cancer and BRCA mutations, providing better outcomes than chemotherapy, such as complete responses and improved quality of life. ^{1 2 3 4 5}

Is Talazoparib safe for humans?

Talazoparib has shown promising safety in patients with advanced breast cancer, as reported in the ABRAZO phase 2 trial. It is approved by the FDA and EMA for certain types of breast cancer, indicating it has undergone safety evaluations. ^{1 2 4 6 7}

How is the drug Talazoparib different from other breast cancer treatments?

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, particularly in patients with BRCA mutations. This makes it different from traditional chemotherapy, which does not target specific genetic mutations. ^{1 2 3 4 7}

Research Team

Neelima Vidula, M.D.

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Talazoparib (PARP Inhibitor)

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.

Participant Groups

Group I: Talazoparib Experimental Treatment 1 Intervention

-Talazoparib will be provided as capsules for oral administration daily

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

Findings from Research

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 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]

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 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 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]

References

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

Talazoparib: First Global Approval. [2020]

2. England 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. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Talazoparib Bests Chemo for Breast Cancer. [2019]

6. Spain pubmed.ncbi.nlm.nih.gov

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

7. 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]