ZEN-3694 + Talazoparib for Cancer

Recruiting at 36 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

Trial Summary

What is the purpose of this trial?

This trial tests if combining ZEN-3694 and talazoparib can shrink advanced tumors that don't respond to standard treatments. ZEN-3694 blocks proteins that help tumors grow, and talazoparib stops cancer cells from fixing their damaged DNA, causing them to die. The study also looks at how patients' genes affect their response to this treatment. Talazoparib is a potent PARP inhibitor that has shown significant efficacy in treating advanced BRCA1 and BRCA2 mutated breast cancer.

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 the combination of ZEN-3694 and Talazoparib safe for humans?

Talazoparib has been shown to have a manageable safety profile in patients with certain types of cancer, such as breast cancer and prostate cancer, according to clinical studies. It has been approved for use in these conditions, indicating that it is generally considered safe when used as directed. ^{1 2 3 4 5}

What makes the drug ZEN-3694 + Talazoparib unique for cancer treatment?

The combination of ZEN-3694 and Talazoparib is unique because it combines a BET inhibitor (ZEN-3694) with a PARP inhibitor (Talazoparib), potentially enhancing the effectiveness of cancer treatment by targeting different pathways involved in cancer cell survival and DNA repair. ^{1 2 3 4 6}

Research Team

Timothy Yap

Principal Investigator

University of Texas MD Anderson Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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-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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

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

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

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

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

Talazoparib: First Global Approval. [2020]

4. 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]

5. England 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. [2021]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Talazoparib Loaded Solid Lipid Nanoparticles: Preparation, Characterization and Evaluation of the Therapeutic Efficacy In vitro. [2020]