Talazoparib for Advanced Breast Cancer

Overseen By Nuzhat Shaikh

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: PARP inhibitors

Disqualifiers: Active brain metastases, BRCA mutations, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This purpose of this study is to test if talazoparib is safe and evaluate its response to advanced breast cancer associated with mutation of gene called PALB.

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

The trial protocol does not specify if you must stop taking your current medications. However, there is a required 21-day washout period from previous treatments before starting the trial.

What data supports the idea that Talazoparib for Advanced Breast Cancer is an effective drug?

The available research shows that Talazoparib is effective for treating advanced breast cancer, especially in patients with specific genetic mutations called BRCA mutations. In studies, Talazoparib was found to be more effective than standard chemotherapy, leading to better outcomes for patients. It helped some patients achieve complete responses, meaning their cancer was no longer detectable, and it also improved their quality of life. Additionally, Talazoparib was shown to be promising in both preclinical and clinical studies, offering significant benefits compared to other similar drugs. ^{1 2 3 4 5}

What safety data is available for Talazoparib in treating advanced breast cancer?

Talazoparib, also known as Talzenna, BMN-673, and Talazoparib Tosylate, has been evaluated for safety in several studies. It has been approved by the FDA and EMA for treating germline BRCA-mutated locally advanced or metastatic breast cancer. The ABRAZO phase 2 trial reported promising efficacy and safety, with patient-reported outcomes indicating a manageable safety profile. Additionally, Talazoparib has been studied for its metabolic stability and toxicity, supporting its use in patients with BRCA-positive breast cancer. ^{1 2 3 4 6}

Is the drug Talazoparib Tosylate a promising treatment for advanced breast cancer?

Yes, Talazoparib Tosylate is a promising drug for advanced breast cancer, especially for patients with specific genetic mutations (BRCA mutations). It has been approved by major health agencies like the FDA and EMA because it shows better results compared to other treatments. It works by targeting cancer cells more effectively, offering significant benefits to patients. ^{1 2 3 7 8}

Research Team

Melinda Telli

Principal Investigator

Stanford Universiy

Eligibility Criteria

This trial is for adults with advanced breast cancer linked to a PALB2 gene mutation. Participants can have had up to three prior treatments, must be able to take pills, and women of childbearing age need a negative pregnancy test and use contraception. People are excluded if pregnant, breastfeeding, previously treated with PARP inhibitors, or have certain brain metastases or other conditions that could affect safety.

Inclusion Criteria

My cancer can be measured by scans and I've had the required scans recently.

My liver functions are within the required limits.

I am a woman who can have children, have a negative pregnancy test, and agree to more tests during the study.

Exclusion Criteria

Pregnant or breastfeeding patients

I have been treated with a PARP inhibitor before.

I have brain metastases or leptomeningeal carcinomatosis but am stable and not on high-dose steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talazoparib 1 mg/day for 24 cycles (28 days per cycle), continuing until withdrawn or discontinued

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Talazoparib Tosylate

Trial Overview The study tests the safety and effectiveness of Talazoparib Tosylate in treating advanced breast cancer associated with PALB2 mutations. It's an oral medication given as monotherapy, meaning it's used alone without combining it with other drugs.

Participant Groups

Group I: Talazoparib Arm Experimental Treatment 1 Intervention

Talazoparib 1 mg/day for 24 cycles (28 days per cycle), continuing until withdrawn or discontinued, eg, until RECIST 1.1 progression or unacceptable toxicity.

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

Approved in European Union as Talzenna for:

• Germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer
• Metastatic castration-resistant prostate cancer (mCRPC) in adults

Approved in United States as Talzenna for:

• Germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer
• HRR Gene-mutated metastatic castration-resistant prostate cancer (mCRPC)

Approved in Canada as Talzenna for:

• BRCA-mutated breast cancer

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

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 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 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]

Talazoparib (TZB) is a new FDA-approved treatment for metastatic breast cancer in patients with BRCA mutations, but it is slowly metabolized by the liver, which raises concerns about potential bioaccumulation and toxicity with long-term use.

The study developed a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to assess TZB's metabolic stability, confirming its low metabolic rate and suggesting the need for monitoring plasma levels during extended treatment to avoid adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Stability Assessment of New PARP Inhibitor Talazoparib Using Validated LC-MS/MS Methodology: In silico Metabolic Vulnerability and Toxicity Studies. Attwa, MW., Kadi, AA., Abdelhameed, AS., et al.[2022]

In a study of 9 patients with advanced solid tumors and BRCA1/2 mutations, talazoparib treatment led to significant intra-tumoral DNA damage response, with 67% of evaluable patients showing a nuclear γH2AX response and 83% demonstrating strong suppression of PARylation after just 8 days.

The overall response rate (ORR) for talazoparib was 55%, with partial responses lasting a median of six treatment cycles, indicating its efficacy as a targeted therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of the PARP inhibitor talazoparib (MDV3800, BMN 673) in patients with BRCA-mutated advanced solid tumors. Mittra, A., Coyne, GHOS., Zlott, J., et al.[2023]

Talazoparib-loaded solid lipid nanoparticles (BMN 673-SLNs) demonstrated significant cytotoxic effects against BRCA1 deficient Triple Negative Breast Cancer (TNBC) cell lines, showing higher apoptotic rates compared to the free drug BMN 673, indicating enhanced therapeutic potential.

BMN 673-SLNs exhibited improved stability and reduced toxicity to normal cells (MCF-10A) while maintaining efficacy against resistant cancer cells, suggesting a promising strategy for targeting drug-resistant TNBC with minimized side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib Loaded Solid Lipid Nanoparticles: Preparation, Characterization and Evaluation of the Therapeutic Efficacy In vitro. Eskiler, GG., Cecener, G., Dikmen, G., et al.[2020]

References

1. Spain pubmed.ncbi.nlm.nih.gov

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

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

Talazoparib: First Global Approval. [2020]

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

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

4. 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]

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

Talazoparib Bests Chemo for Breast Cancer. [2019]

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

Metabolic Stability Assessment of New PARP Inhibitor Talazoparib Using Validated LC-MS/MS Methodology: In silico Metabolic Vulnerability and Toxicity Studies. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of the PARP inhibitor talazoparib (MDV3800, BMN 673) in patients with BRCA-mutated advanced solid tumors. [2023]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Talazoparib Loaded Solid Lipid Nanoparticles: Preparation, Characterization and Evaluation of the Therapeutic Efficacy In vitro. [2020]