What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving BET inhibitors like ZEN003694 and PARP inhibitors like Talazoparib, are associated with several side effects. BET inhibitors can cause fatigue, gastrointestinal issues (nausea, vomiting, diarrhea), and hematologic toxicities such as anemia and thrombocytopenia. PARP inhibitors are known to cause nausea, fatigue, anemia, neutropenia, thrombocytopenia, and gastrointestinal disturbances. Patients undergoing these treatments should be monitored for these potential side effects.

What prior FDA approvals exist?

Talazoparib, a PARP inhibitor, has been approved by the FDA for the treatment of breast cancer, particularly in patients with germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer. Other PARP inhibitors like Olaparib have also received FDA approval for similar indications. While BET inhibitors like ZEN003694 are still under investigation, the combination of PARP inhibitors with other agents represents a promising area of research in breast cancer treatment.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: 1) Antibody-drug conjugates (ADCs) such as Trastuzumab Deruxtecan, which targets HER2-positive breast cancer. 2) CDK4/6 inhibitors like Abemaciclib, which are effective in HR-positive, HER2-negative breast cancer. 3) Immunotherapy agents such as Pembrolizumab, particularly for triple-negative breast cancer (TNBC). 4) PI3K inhibitors like Alpelisib for PIK3CA-mutated breast cancer. These alternatives have shown significant efficacy in recent clinical trials and offer new hope for breast cancer patients.

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PARP Inhibitor

ZEN003694 + Talazoparib for Triple Negative Breast Cancer (TNBC Trial)

Phase 2

Waitlist Available

Research Sponsored by Zenith Epigenetics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Have received TROP2-ADC therapy for unresectable locally advanced or metastatic disease (Expansion Cohort A)

Must not have

Radiation to >25% of the bone marrow (Parts 1 and 2 only)

Prior anticancer therapy within 3 weeks from the start of study drug (except for nitrosoureas and mitomycin C within 6 weeks from start of study drug)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from screening up to 18 months

Awards & highlights

Summary

This trial is testing a new drug combination (ZEN003694 and Talazoparib) in patients with a difficult-to-treat type of breast cancer. The goal is to see if these drugs can work together to stop cancer growth and make it harder for cancer cells to repair themselves.

Who is the study for?

Adults with triple-negative breast cancer (TNBC) that's advanced or returned and doesn't have BRCA1/2 mutations. They must have tried chemotherapy before, can't be candidates for hormone therapy, and should not have certain blood clotting medication use or untreated brain metastases. Specific cohorts include those who've had TROP2-ADC treatment or are naive to it.

What is being tested?

The trial is testing ZEN003694 alone and combined with Talazoparib in TNBC patients. It has two parts: dose escalation to find safe levels, followed by a Simon 2-Stage design to assess effectiveness. There are three groups based on prior treatments like TROP2-ADC.

What are the potential side effects?

Potential side effects aren't detailed here but may include typical reactions to cancer drugs such as nausea, fatigue, blood count changes, risk of infection, liver function issues, and possibly others specific to the study drugs' profiles.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have received TROP2-ADC therapy for my advanced or metastatic disease.

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My breast cancer is triple-negative and has spread or come back.

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I have undergone at least one chemotherapy treatment.

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My condition worsened despite previous treatments.

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I have undergone at least one round of chemotherapy.

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I've had treatment for advanced cancer but not with TROP2-ADC.

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My breast cancer is triple-negative and not responsive to hormones or HER2 treatments.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not had radiation to more than 25% of my bone marrow.

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I haven't had cancer treatment in the last 3 weeks, or 6 weeks for specific drugs.

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I have been treated with a PARP inhibitor before.

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I have a genetic mutation in BRCA1 or BRCA2.

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I am taking oral blood thinners that target Factor Xa or Factor IIa.

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I have brain metastases that are getting worse, causing symptoms, or untreated.

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I have a wound, ulcer, or bone fracture that is not healing.

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My brain metastases have been stable and untreated for at least 3 months.

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My cancer got worse during platinum-based treatment.

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I have not had bone-targeted radionuclide therapy in the last 6 weeks.

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I am taking or will take medication that strongly affects certain liver enzymes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from screening up to 18 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from screening up to 18 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from screening up to 18 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Expansion Cohort A: Objective response rate (ORR) by RECIST v1.1 (CR or PR)

Part 1: Incidence of dose-limiting toxicities (DLT)

Part 2: Clinical benefit rate (CBR)

Secondary study objectives

Part 1, Expansion Cohorts A and C: Clinical benefit rate (CBR)

Part 1, Part 2, Expansion Cohorts A and C: Evaluate median progression-free survival

Part 1, Part 2, and Expansion Cohort C: Objective response rate (ORR)

+7 more

Side effects data

From 2019 Phase 1 & 2 trial • 75 Patients • NCT02711956

58%

Visual impairment

52%

Nausea

42%

Fatigue

32%

Decreased appetite

32%

Dysgeusia

19%

Thrombocytopenia

16%

Diarrhea

10%

Taste disorder

10%

Weight decreased

10%

Photopsia

10%

Vomiting

10%

Photosensitivity reaction

10%

Constipation

10%

Dizziness

10%

Blood creatinine increased

Spinal cord compression

Musculoskeletal pain

Myocardial ischaemia

Acute kidney injury

Intervertebral discitis

Rash maculopapular

100%

80%

60%

40%

20%

Study treatment Arm

DE/DC A+B 96 mg ZEN003694 + Enzalutamide

DE A+B 36 mg ZEN003694 + Enzalutamide

DE/DC A+B 48 mg ZEN003694 + Enzalutamide

DE A+B 60 mg ZEN003694 + Enzalutamide

DE A+B 72 mg ZEN003694 + Enzalutamide

DE A+B 120 mg ZEN003694 + Enzalutamide

DE A+B 144 mg ZEN003694 + Enzalutamide

Trial Design

4Treatment groups

Experimental Treatment

Group I: Part 1 and Part 2Experimental Treatment2 Interventions

ZEN003694 will be administered PO QD with Talazoparib PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

Group II: Expansion Cohort C - Combination Treatment in TROP2-ADC-naïve patientsExperimental Treatment2 Interventions

ZEN003694 will be administered PO QD with Talazoparib PO QD at the RP2D in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in China only.

Group III: Expansion Cohort B - ZEN003694 MonotherapyExperimental Treatment1 Intervention

ZEN003694 will be administered PO QD as monotherapy at the RP2D in 28-day cycles with the option to cross-over to combination treatment of ZEN003694 PO QD with Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

Group IV: Expansion Cohort A - Combination Treatment in post-TROP2-ADC patientsExperimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ZEN003694

2016

Completed Phase 2

~120

Talazoparib

2021

Completed Phase 2

~2820

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Breast cancer treatments often target specific molecular pathways to inhibit cancer cell growth and survival. BET inhibitors like ZEN003694 work by blocking the BET family of proteins, which are involved in regulating gene expression that promotes cancer cell proliferation. PARP inhibitors such as Talazoparib prevent the repair of DNA damage in cancer cells, leading to cell death, particularly in cells deficient in homologous recombination repair mechanisms. These targeted therapies are crucial for breast cancer patients as they offer more personalized treatment options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.