ZEN003694 + Talazoparib for Ovarian Cancer

Overseen By Lucia Borasso, BSN

Age: 18+

Sex: Female

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 48 months

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two oral medications, Talazoparib (also known as Talzenna) and ZEN003694, to determine their effectiveness in treating recurrent ovarian, fallopian tube, or primary peritoneal cancer. The goal is to assess the safety and efficacy of these drugs when used together. It is open to females with any type of recurrent ovarian cancer, regardless of response to platinum-based treatments, who have previously tried certain cancer therapies. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of ZEN003694 and talazoparib has been explored for treating various cancers. In earlier studies, this combination helped stop tumor growth, especially in patients who had already tried other treatments. However, complete safety information for this combination in ovarian cancer is not yet available.

Since this trial is in Phase 2, the treatment has already passed initial safety tests in earlier phases, indicating some level of safety and tolerability. More information is needed to confirm this specifically for ovarian cancer. The FDA has already approved talazoparib alone for other uses, which offers some reassurance about its safety. Overall, while this combination shows potential, participants should be aware that full safety data for this specific use is still being collected. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ZEN003694 and Talazoparib for ovarian cancer because it offers a unique approach by targeting two key mechanisms. Unlike standard treatments like chemotherapy, which attack rapidly dividing cells, this combination focuses on inhibiting specific proteins that contribute to cancer cell survival and DNA repair. ZEN003694 is a BET inhibitor, which helps disrupt cancer cell communication, while Talazoparib is a PARP inhibitor, preventing cancer cells from repairing themselves. Together, they aim to deliver a more targeted attack on cancer cells, potentially leading to more effective outcomes with fewer side effects.

What evidence suggests that ZEN003694 + Talazoparib could be effective for ovarian cancer?

Research shows that using ZEN003694 with talazoparib may help treat certain cancers. In this trial, participants will receive this combination. Studies have found that it can slow or stop tumor growth in people with advanced cancer. ZEN003694 reduces the number of cancer cells, while talazoparib damages their DNA, making survival difficult. Early results in similar cancers, such as breast cancer, indicate that this combination can fight cancer, suggesting it might also be effective for ovarian cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Alexander B Olawaiye, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Talazoparib
• ZEN003694

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.

How Is the Trial Designed?

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

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?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-02915

Trial Combination therapy with ZEN-3694 and talazoparib may be effective at slowing or stopping tumor growth in patients with advanced cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05071937

Study Details | NCT05071937 | ZEN003694 Combined ... ZEN003694 has shown promising activity in the treatment of solid tumors and hematologic (blood) cancers by reducing the multiplication of cancer cells. Drug : ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.1023

A phase 1b/2 study of the BET inhibitor ZEN-3694 in ... Conclusions: Combination of ZEN-3694 and talazoparib demonstrated anti-cancer activity in pretreated mTNBC WT gBRCA1/2 patients. All ...

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT05327010

Testing the Combination of the Anti-cancer Drugs ... Combination therapy with ZEN-3694 and talazoparib may be effective at slowing or stopping tumor growth in patients with advanced cancer.

5. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=002041-C&&query=

NIH Clinical Center: Search the Studies Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with talazoparib in patients <18 years of age ...

6. withpower.com withpower.com/trial/phase-3-ovarian-neoplasms-9-2021-02e95

ZEN003694 + Talazoparib 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 ...