ZEN-3694 + Talazoparib for Cancer

Recruiting at 38 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, Proton-pump-inhibitors, Factor Xa inhibitors, Factor IIa inhibitors

Disqualifiers: Uncontrolled illness, Psychiatric illness, Pregnancy, 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: 3

Duration: 28 days per cycle

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug combination of ZEN-3694 and talazoparib (Talzenna) can shrink tumors in individuals with advanced cancer when standard treatments fail. ZEN-3694 may halt tumor growth by targeting a protein essential to cancer cells, while talazoparib blocks an enzyme that aids in cancer cell repair. The trial also aims to understand how patients' genes might influence their response to these drugs. This trial may suit individuals with advanced cancer who have specific genetic mutations and have previously tried other treatments without success. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are strong inhibitors or inducers of CYP3A4 or P-gp, strong inhibitors of BCRP, sensitive substrates of CYP1A2, proton-pump-inhibitors, and herbal medications at least 7 days before starting the trial. You should consult with your doctor about any other medications you are taking to ensure they do not interact with the trial drugs.

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

Research has shown that the combination of ZEN-3694 and talazoparib has been tested for safety in patients with certain types of cancer. In earlier studies, patients generally tolerated the treatment well, although some experienced side effects. The most common side effects included tiredness and nausea. More serious side effects were rare but were carefully monitored by medical teams.

These two drugs work together to stop cancer from growing. ZEN-3694 blocks proteins that aid cancer growth, while talazoparib prevents cancer cells from repairing their DNA. This combination aims to kill cancer cells more effectively.

The trial is currently ongoing, so safety is still being evaluated. However, ZEN-3694 and talazoparib have shown promise in earlier research. These findings contribute to understanding the potential safety and effectiveness of this treatment for other patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ZEN-3694 and Talazoparib because they work together in a unique way to tackle cancer. Talazoparib is a PARP inhibitor, which means it targets and shuts down a protein that cancer cells often rely on to repair their DNA. By doing this, it can help kill cancer cells while sparing normal cells. ZEN-3694, on the other hand, targets a protein called BET, which is involved in cancer cell growth and survival. By combining these two treatments, there's potential for a powerful one-two punch against cancer cells, offering hope for more effective treatment outcomes compared to standard therapies.

What evidence suggests that the combination of ZEN-3694 and talazoparib could be effective for advanced cancer?

Research has shown that the combination of ZEN-3694 and talazoparib, which participants in this trial will receive, may help fight cancer. Studies have found that this treatment can slow tumor growth in patients with aggressive, metastatic cancers. ZEN-3694 blocks proteins that aid cancer cell growth, while talazoparib prevents cancer cells from repairing damaged DNA. This combination has demonstrated anti-cancer effects, particularly in patients previously treated for certain types of breast cancer. The treatment aims to slow or stop tumor growth in advanced cancer cases. ^{1 2 3 4 6}

Who Is on the Research Team?

Timothy Yap

Principal Investigator

University of Texas MD Anderson Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that are metastatic or unresectable, where standard treatments have failed. Participants must meet specific health criteria like adequate blood cell counts and organ function, agree to use contraception, and not be pregnant or breastfeeding. Some cohorts require genetic mutations in cancer-related genes (e.g., BRCA1/2 or KRAS). Prior therapies are allowed but with certain time frames for recovery.

Inclusion Criteria

I have a tumor that can be safely biopsied and at least one tumor that can be measured.

I agree to use contraception during and for 4 months after the study.

Platelets >= 150,000/mcL

Exclusion Criteria

Patients who are involved in the planning and/or conduct of the study

Patients with psychiatric illness/social situations that would limit compliance with study requirements

I have not been treated with ZEN-3694 or any experimental BET inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ZEN-3694 and talazoparib orally once daily on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Regular visits for diagnostic imaging, blood sample collection, and tumor biopsy

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for up to 2 years.

Up to 2 years

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Talazoparib
• ZEN-3694

Trial Overview The trial is testing the combination of ZEN-3694, a BET protein inhibitor which may stop tumor growth by targeting overproduced proteins in cancer cells, and Talazoparib, a PARP enzyme inhibitor that prevents cancer cells from repairing their DNA. The study also examines how patients' genetics affect their response to this treatment.

How Is the Trial Designed?

Group I: Treatment (ZEN-3694, talazoparib) Experimental Treatment 5 Interventions

Patients receive ZEN-3694 PO QD and 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 diagnostic imaging, blood sample collection, and tumor biopsy 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

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]

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 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 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]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03901469

NCT03901469 | A Study of ZEN003694 and Talazoparib in ... This is a two-part open label, non-randomized, Phase 2, study of ZEN003694 in combination with Talazoparib in patients with TNBC without germline mutations ...

3. 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. Eligibility Criteria ...

4. 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 : ...

5. ascopubs.org ascopubs.org/doi/abs/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.

6. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=002041-C&&query=1

Protocol Details -Age >=18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with talazoparib in patients ...