ZEN003694 + Talazoparib for Ovarian Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Alexander B Olawaiye, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Alexander B Olawaiye, MD

Must not be taking: CYP3A4 inhibitors, P-gp inhibitors, Factor Xa inhibitors, Factor IIa inhibitors

Disqualifiers: Brain metastases, Cardiac disease, Others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two oral drugs, ZEN003694 and talazoparib, in patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer. ZEN003694 helps stop cancer cells from growing, while talazoparib blocks an enzyme that cancer cells need to repair themselves. The goal is to see how well these drugs work together in this specific group of patients.

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

The trial requires you to stop using medications that are strong inhibitors or inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows at least 7 days before starting the study drug. You also cannot use strong P-gp inhibitors within 7 days before or during the study, and certain blood thinners are not allowed.

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

Research shows that Talazoparib, a drug that helps prevent cancer cells from repairing themselves, has been effective in treating breast cancer with certain genetic mutations. Additionally, it has potential for treating ovarian cancer with similar genetic issues, although its use is limited by side effects. ^{1 2 3 4 5}

Is the combination of ZEN003694 and Talazoparib safe for humans?

Talazoparib has been used in treating breast and prostate cancer, showing antitumor activity with a manageable safety profile, meaning it has been generally safe for patients in these studies. ^{1 2 3 4 6}

What makes the drug ZEN003694 + Talazoparib unique for ovarian cancer?

The combination of ZEN003694 and Talazoparib is unique for ovarian cancer because it targets the BRCA mutation, which is present in over 15% of ovarian cancer patients, using a PARP inhibitor (a drug that blocks an enzyme involved in DNA repair) like Talazoparib. This approach is novel as it directly targets the genetic weakness in cancer cells, potentially offering a more effective treatment option for those with BRCA mutations. ^{1 2 3 5 6}

Research Team

Alexander B Olawaiye, MD

Principal Investigator

UPMC Hillman Cancer Center

Eligibility Criteria

This trial is for women over 18 with recurrent ovarian, fallopian tube, or primary peritoneal carcinoma. Participants must have had prior therapy with PARPi, any number of previous cancer treatments, measurable disease, known BRCA1/2 status and meet specific health criteria including adequate blood counts and organ function. They cannot be pregnant or breastfeeding and must use effective contraception if of childbearing potential.

Inclusion Criteria

I have undergone any number of cancer treatments.

I know my BRCA1/2 gene status.

I have been treated with PARP inhibitors before.

Exclusion Criteria

Concurrent participation in another clinical investigational treatment trial

I haven't had chemotherapy or radiation in the last 3 weeks.

I have not had a heart attack or unstable chest pain in the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ZEN003694 and Talazoparib daily in 28-day cycles

Up to 48 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Up to 6 years

Treatment Details

Interventions

• Talazoparib (PARP Inhibitor)
• ZEN003694 (Other)

Trial Overview The study tests the combination of two oral drugs: ZEN003694 and Talazoparib given daily in cycles lasting 28 days to treat recurrent ovarian cancer. It's an open-label Phase 2 trial which means everyone gets the treatment and knows what they are receiving.

Participant Groups

Group I: ZEN003694 + Talazoparib Experimental Treatment 2 Interventions

ZEN003694: 48.0 mg daily (oral) in 28-day cycles Talazoparib: 0.75 mg daily (oral) at the same time as ZEN003694

Who Is Running the Clinical Trial?

Alexander B Olawaiye, MD

Lead Sponsor

Trials

4

Recruited

130+

Haider Mahdi

Lead Sponsor

Trials

6

Recruited

130+

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

Zenith Epigenetics

Industry Sponsor

Trials

10

Recruited

590+

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 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 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]

The novel TLZ-loaded PLGA implant (InCeT-TLZ) provides a sustained release of Talazoparib directly into the peritoneal cavity, significantly improving survival rates in a mouse model of BRCA-mutated metastatic ovarian cancer, with treated mice showing doubled survival compared to controls.

InCeT-TLZ minimizes systemic side effects typically associated with chemotherapy, as no significant toxicity was observed in surrounding organs, making it a promising localized treatment option for ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer. Yang, S., Green, A., Brown, N., et al.[2023]

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]

References

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

Talazoparib: First Global Approval. [2020]

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

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

3. Spain pubmed.ncbi.nlm.nih.gov

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

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer. [2023]

6. Switzerland 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. [2023]