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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of talazoparib, a medication for advanced breast cancer with a specific PALB2 gene mutation. The goal is to evaluate how well this treatment works for individuals whose cancer is HER2 negative and has either spread or recurred after treatment. It suits those with HER2 negative advanced breast cancer who have the PALB2 mutation and have not previously received a PARP inhibitor. Participants will take talazoparib daily in cycles, continuing as long as it remains effective and safe. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that talazoparib is already approved to treat certain types of breast cancer. Studies indicate that most patients tolerate talazoparib well. Common side effects include fatigue and nausea. Some patients might experience more serious effects, such as anemia, which means a low red blood cell count. However, for many patients, the benefits of the drug can outweigh these risks. Overall, talazoparib has shown promising results in treating advanced cancers linked to specific genetic changes. ^{1 2 3 4 5}

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

Talazoparib Tosylate is unique because it targets cancer cells differently than most current treatments for advanced breast cancer. While standard options often involve chemotherapy that attacks all rapidly dividing cells, Talazoparib specifically inhibits a protein called PARP (poly ADP-ribose polymerase). This inhibition is crucial because it prevents cancer cells, especially those with BRCA mutations, from repairing their DNA, leading to their death. Researchers are excited because this targeted approach could mean more effective treatment with potentially fewer side effects than traditional chemotherapy.

What evidence suggests that talazoparib might be an effective treatment for advanced breast cancer?

Research shows that talazoparib, which participants in this trial will receive, holds promise for treating advanced breast cancer, particularly in patients with BRCA mutations. Studies have found that talazoparib is more effective and offers significant benefits for these patients. For those with these genetic mutations, talazoparib has demonstrated a strong ability to fight tumors. While this treatment targets BRCA mutations, its effects on PALB mutations remain under investigation. However, by preventing cancer cells from repairing themselves, it might also benefit those with PALB mutations. ^{1 5 6 7 8}

Who Is on the Research Team?

Melinda Telli

Principal Investigator

Stanford Universiy

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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-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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02401347

NCT02401347 | Phase II Trial of Talazoparib in BRCA1/2 ... Talazoparib has shown promising single-agent anti-tumor efficacy in several BRCA1/2 mutation-associated advanced cancers. The efficacy of PARP inhibition in ...

2. nature.com nature.com/articles/s41698-024-00634-6

Phase II study of talazoparib in advanced cancers with ... Talazoparib demonstrated clinical benefit in selected DDR-altered patients. PTEN mutations/loss patients derived limited clinical benefit.

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/211651Orig1s000MultidisciplineR.pdf

211651Orig1s000 - accessdata.fda.gov Integrated Assessment of Effectiveness. The efficacy of talazoparib in BRCA-mutated HER2-negative breast cancer patients is supported by the ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31347614/

Talazoparib to treat BRCA-positive breast cancer Talazoparib exerted superior efficacy and offered a significant clinical benefit in advanced or metastatic BC patients harboring germline BRCA mutations.

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

Talzenna - accessdata.fda.gov The median number of prior cytotoxic regimens for patients with advanced breast cancer was one; 38% received no prior cytotoxic regimens for advanced or ...

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

Talzenna, INN-talazoparib - EMA Talzenna is indicated as monotherapy for the treatment of adult patients with germline. BRCA1/2-mutations, who have HER2-negative locally advanced or ...

7. oncologynewscentral.com oncologynewscentral.com/drugs/monograph/176318-318057/talazoparib-oral

Talazoparib Oral Currently available evidence indicates that talazoparib therapy is associated with substantially prolonged progression-free survival and improved response rates ...

8. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6fd147f-a77e-4a0b-9280-e82ecc41b4be

Label: TALZENNA- talazoparib capsule, liquid filled - DailyMed TALZENNA is indicated as a single agent for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene ...