What is the mechanism of action of this treatment?

PARP inhibitors, such as Talazoparib, work by preventing the repair of damaged DNA in cancer cells, leading to cell death. Enzyme inhibitors, including Palbociclib, Axitinib, and Crizotinib, block specific enzymes that are essential for cancer cell growth and proliferation. These targeted therapies are important for cancer patients because they can more precisely disrupt cancer cell survival mechanisms, potentially improving treatment efficacy and reducing side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

PARP inhibitors, such as Talazoparib, commonly cause side effects including anemia, nausea, fatigue, and thrombocytopenia. Enzyme inhibitors like Palbociclib often lead to neutropenia, leukopenia, and fatigue. Axitinib, a VEGFR inhibitor, is associated with hypertension, diarrhea, and hand-foot syndrome. Crizotinib, used for ALK-positive cancers, frequently results in vision disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue. Serious toxicities of Crizotinib include hepatotoxicity, interstitial lung disease, and QT-interval prolongation.

What prior FDA approvals exist?

PARP inhibitors like Olaparib, Niraparib, and Rucaparib have received FDA approval for treating cancers such as ovarian and prostate cancer, especially in patients with BRCA mutations. Enzyme inhibitors like Palbociclib (approved for HR-positive, HER2-negative breast cancer), Axitinib (approved for renal cell carcinoma), and Crizotinib (approved for ALK-positive non-small cell lung cancer) have also been approved. These drugs target specific molecular pathways, demonstrating the effectiveness of such targeted therapies in cancer treatment.

What other types of research exist?

Promising novel alternatives for cancer treatment in 2024 include: <ol> <li>Olaparib (PARP Inhibitor) in combination with Abiraterone (Androgen Receptor Inhibitor): This combination has shown efficacy in metastatic castration-resistant prostate cancer with homologous recombination repair deficiency.</li> <li>Pembrolizumab (PD-1 Inhibitor) for tumors with high tumor mutational burden (TMB) or mismatch repair deficiency (dMMR): Effective in various metastatic cancers, including prostate cancer.</li> <li>Venetoclax (BCL-2 Inhibitor) plus Obinutuzumab (Anti-CD20 Monoclonal Antibody): This combination is particularly useful for chronic lymphocytic leukemia and may be explored for other cancers.</li> <li>Zanubrutinib (BTK Inhibitor): Shows promise in chronic lymphocytic leukemia and may be considered for other cancers with similar pathways.</li> </ol>

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Tyrosine Kinase Inhibitor

Talazoparib Combinations for Advanced Cancer

Phase 1

Recruiting

Led By Timothy A Yap

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

ECOG performance status (PS) 0 to 1

Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1

Must not have

Prior anti-cancer therapy within 2 weeks prior to study enrollment or prior radiation therapy within 2 weeks prior to study enrollment

Active infection requiring systemic therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of drugs to treat patients with advanced solid tumors. The treatment aims to find the best dose and understand the benefits and side effects. It works by stopping tumor cells from repairing and growing.

Who is the study for?

This trial is for adults with advanced or metastatic solid tumors who can swallow pills, have no allergies to study drugs, and are not pregnant. They must have specific gene defects related to cancer growth or DNA repair, adequate blood counts and organ function, and a performance status that allows daily activity. Patients with recent treatments or surgeries, uncontrolled infections like hepatitis B/C or HIV, brain metastases needing steroids, other recent malignancies (except prostate cancer in some cases), or those on strong CYP3A4 inhibitors/inducers cannot join.

What is being tested?

The TalaCom Trial is testing the combination of talazoparib (a PARP inhibitor that prevents tumor cells from repairing their DNA) with either palbociclib, axitinib, or crizotinib (drugs that block enzymes needed for cell growth). The goal is to determine the best dose and see if this combo can control tumor growth better than current treatments.

What are the potential side effects?

Potential side effects include nausea, fatigue, low blood counts leading to increased infection risk or bleeding problems. There may also be liver issues indicated by changes in certain blood tests. Specific side effects depend on which drug combination patients receive but could involve high blood pressure with axitinib and vision disorders with crizotinib.

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 can carry out light work.

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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 at least one tumor that can be measured and has not been treated with radiation.

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My white blood cell count is healthy without needing medication or transfusions in the last 2 weeks.

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My cancer has a specific genetic change.

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My cancer has a specific change in the MET, ALK, or ROS1 gene.

Exclusion Criteria

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

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I have not had cancer treatment or radiation in the last 2 weeks.

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I am currently on medication for an infection.

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I need steroids for my brain metastases symptoms.

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I am not allergic to talazoparib or the study drugs I will receive.

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I am not pregnant, breastfeeding, or able to become pregnant and unwilling to use two forms of birth control.

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I do not have uncontrolled hepatitis B or C.

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I have lasting side effects from previous treatments that are moderate or worse.

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I have not had major surgery in the last 4 weeks.

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I have been diagnosed with myelodysplastic syndrome.

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I have HIV/AIDS that is not under control.

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I haven't taken strong CYP3A4 inhibitors or inducers in the last week.

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I have a serious heart condition.

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I cannot swallow pills or have a condition that affects how my body absorbs medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of adverse events

Incidence of dose limiting toxicities

Secondary study objectives

Clinical benefit rate

Duration of response

Objective response

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm III (talazoparib, crizotinib)Experimental Treatment2 Interventions

Patients receive talazoparib PO QD on days 1-28 and crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.

Group II: Arm II (talazoparib, axitinib)Experimental Treatment2 Interventions

Patients receive talazoparib PO QD on days 1-28 and axitinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.

Group III: Arm I (talazoparib, palbociclib)Experimental Treatment2 Interventions

Patients receive talazoparib PO QD on days 1-21 or 1-28 and palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Talazoparib Tosylate

2020

Completed Phase 2

~100

Axitinib

2020

Completed Phase 2

~3050

Crizotinib

2014

Completed Phase 3

~2960

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

PARP inhibitors, such as Talazoparib, work by preventing the repair of damaged DNA in cancer cells, leading to cell death. Enzyme inhibitors, including Palbociclib, Axitinib, and Crizotinib, block specific enzymes that are essential for cancer cell growth and proliferation. These targeted therapies are important for cancer patients because they can more precisely disrupt cancer cell survival mechanisms, potentially improving treatment efficacy and reducing side effects compared to traditional chemotherapy.

Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol.PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.