Talazoparib for Advanced Cancer

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: GnRH agonists

Must not be taking: Investigational agents

Disqualifiers: Active brain metastases, Uncontrolled illness, 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: 28 days per cycle

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of talazoparib for individuals with advanced cancer and specific genetic changes affecting DNA repair. Talazoparib, a targeted therapy, blocks a protein called PARP, which aids cancer cells in repairing damaged DNA, potentially leading to their death. The trial is open to those with solid tumors and specific genetic mutations in DNA repair genes, whose cancer has worsened after standard treatments or who have no other treatment options. Participants will take talazoparib in cycles and may need to undergo biopsies, blood tests, and scans during the study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important cancer research.

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, if you are taking medications that might affect the activity of talazoparib, the principal investigator will review your case to determine eligibility. Patients on certain anticoagulants like warfarin are excluded, but low-dose warfarin is allowed.

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

Research has shown that talazoparib has a predictable safety profile. In earlier studies with patients who had advanced breast cancer, the most common side effects included tiredness, low red blood cell count (anemia), and nausea, occurring in more than 20% of patients. Serious side effects were similar to those expected with this type of treatment and can usually be managed by adjusting the dose.

The FDA has already approved talazoparib for treating certain breast cancers, indicating a level of safety in humans. While the treatment may cause some side effects, they are generally manageable. Prospective participants should always discuss potential risks with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about talazoparib for advanced cancer because it works differently from many traditional treatments. While most cancer therapies target rapidly dividing cells, talazoparib is a PARP inhibitor, which means it targets a specific protein involved in DNA repair. By blocking this protein, talazoparib makes it harder for cancer cells to fix their damaged DNA, leading to their death. This targeted approach can be particularly beneficial for patients with specific genetic mutations, offering a more personalized treatment option.

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

Research has shown that talazoparib, a type of drug called a PARP inhibitor, can help treat some advanced cancers. In people with advanced breast cancer, one study found that 50% of patients experienced their cancer shrinking or disappearing. Another study showed that adding talazoparib to the treatment for advanced prostate cancer resulted in an average survival time of 45.8 months. Talazoparib blocks a protein that helps fix damaged DNA in cancer cells, leading to the death of these cells. These studies suggest that talazoparib could be a promising option for patients with certain gene mutations affecting DNA repair. Participants in this trial will receive talazoparib as the investigational treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

A P Chen

Principal Investigator

National Cancer Institute LAO

Are You a Good Fit for This Trial?

Adults with advanced cancer and specific DNA repair gene mutations, who have progressed after standard therapy or lack treatment options. They must be able to swallow pills, have a life expectancy over 3 months, acceptable blood counts and organ function, and women must use contraception. Excluded are those with HIV, recent chemotherapy or radiotherapy, lactating women, pregnant women, prior talazoparib treatment.

Inclusion Criteria

Your absolute neutrophil count is at least 1,500 per microliter.

I am using a reliable birth control method.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

You are taking any other experimental medications.

I have not had chemotherapy or radiotherapy recently.

I have received monoclonal antibody therapy recently.

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 of each cycle, with cycles repeating every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and blood sample collection, as well as CT scan or MRI throughout the study.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days post-treatment.

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Talazoparib

Trial Overview The trial is testing Talazoparib's effectiveness in patients with advanced cancers that have spread and contain DNA repair gene mutations. It involves taking the drug to see if it prevents cancer cells from repairing their DNA damage which may lead to cell death.

How Is the Trial Designed?

Group I: Treatment (talazoparib) Experimental Treatment 5 Interventions

Patients receive talazoparib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and blood sample collection as well as CT scan or MRI throughout the study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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 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]

In the TALAPRO-1 study involving 97 men with metastatic castration-resistant prostate cancer (mCRPC), talazoparib significantly improved health-related quality of life (HRQoL) and reduced pain levels, particularly in patients with BRCA1/2 mutations.

The study found that 84% of all patients and 83% of those with BRCA1/2 mutations did not experience a deterioration in worst pain after 12 months of treatment, indicating a high probability of maintaining pain relief while receiving talazoparib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1. Saad, F., de Bono, J., Barthélémy, P., et al.[2023]

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]

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 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]

Citations

1. 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 ...

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

People with metastatic castration-resistant prostate cancer. Participants treated with Talzenna and Xtandi survived an average of 45 months from the start of treatment. · Participants treated with placebo ...

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

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

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. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizers-talzennar-combination-xtandir-improves-survival

Pfizer's TALZENNA® in Combination with XTANDI® ... After more than four years of median follow-up (52.5 months), the median OS in cohort 1 was 45.8 months with TALZENNA in combination with XTANDI ...

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

Safety Profile | TALZENNA® (talazoparib) HCP Site Talazoparib in patients with a germline BRCA-mutated advanced breast cancer: detailed safety analyses from the phase III EMBRACA trial. Oncologist. 2019;24 ...

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

Talazoparib in Patients with a Germline BRCA‐Mutated ... Clinical trial data indicate a consistent and therefore predictable safety profile for talazoparib. Talazoparib‐induced AEs can be readily managed by dose ...

8. pfizeroncologycongresshub.com pfizeroncologycongresshub.com/files/PP-TAL-USA-0434-Talzenna-Patient-Profiles-Digital-Production-Files_v5-0_11-5-21_IMsci.pdf

TALZENNA® (talazoparib) Patient Profiles The most common adverse reactions (≥20%) of any grade for TALZENNA vs chemotherapy were fatigue (62% vs 50%), anemia (53% vs 18%), nausea (49% vs 47%), ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/211651Orig1s000RiskR.pdf

211651Orig1s000 - accessdata.fda.gov HER2-negative locally advanced or metastatic breast cancer ... The SAEs seen with talazoparib treatment are similar to the known safety profile.

10. ahdbonline.com ahdbonline.com/select-drug-profiles/talzenna-talazoparib-new-parp-inhibitor-approved-for-the-treatment-of-her2-negative-advanced-breast-cancer-with-germline-brca-mutation

Talzenna (Talazoparib) New PARP Inhibitor Approved for ... The safety profile of talazoparib is based on data from 286 patients in the EMBRACA study. ... Talazoparib in patients with advanced breast cancer and a ...