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Protocol Details

A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage Response

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 120 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women


DNA Damage Repair;
synthetic lethality;
PARP trapping;
basket trial

Recruitment Keyword(s)



Solid Tumors

Investigational Drug(s)


Investigational Device(s)



Drug: talazoparib

Supporting Site

National Cancer Institute


People with advanced cancer are usually treated with surgery, radiation, immunotherapy drugs, or chemotherapy drugs. Talazoparib is a type of drug called a PARP inhibitor. It prevents DNA repair and has shown anticancer activity in early clinical trials. Researchers want to learn more about how it works in different types of patients.


To find out how talazoparib works in tumor cells and if it works differently in people who have or have not already been treated with another PARP inhibitor.


Adults ages 18 and older with locally advanced or metastatic solid tumors, who have a gene variation that changes how their tumors are able to repair DNA


Participants will be screened with a medical history and physical exam. Their medical records will be reviewed. Their ability to do daily activities will be assessed. They will give blood samples. Screening tests will be repeated during the study.

Participants tumors will be measured. They will have tumor biopsies.

Participants samples will be used for gene testing.

Participants will be put into 1 of 2 groups: those who have never had a PARP inhibitor and those who have had a PARP inhibitor.

Participants will take talazoparib by mouth daily. It is given in cycles that are 4 weeks (28 days) long. They will get the study drug for as long as their cancer does not get worse, they can tolerate the side effects, and they choose to stay on the study.

After treatment ends, participants condition will be followed. They will be watched for side effects. They will be contacted once about 30 days after treatment ends.

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Patients with the following germline or somatic genetic aberrations will be eligible based on compelling preclinical and/or clinical data suggesting that these deleterious mutations confer sensitivity to PARP inhibitors; no more than 6 patients (across both cohorts) with an eligibility mutation in any one gene will be enrolled. The list of eligible mutations is restricted to genes from the NCI-MPACT protocol aMOIs panel for temozolomide plus veliparib (NCT01827384), published results from TRITON2: A Phase 2 Study of Rucaparib in Patients with Metastatic Castration-Resistant Prostate Cancer Associated with Homologous Recombination Repair Gene Alterations [75], and the following ongoing clinical trials:

- Rucaparib in Patients with Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (TRIUMPH) (NCT03413995)

- Olaparib in Treating Patients with Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations (NCT04042831)

- Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Muations (ORCHID) (NCT03786796)

- Deleterious BRCA1 or BRCA2 mutations

- Loss of function mutations (including novel loss of function frameshift or nonsense mutations) in the following Fanconi anemia genes: FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN

-A known functional mutation (including novel loss of function frameshift or nonsense mutations) in any of the following DDR genes: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, CDK12, CHK1, CHK2, IDH1, IDH2, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54L.

Age greater than or equal to18 years of age.

ECOG performance status less than or equal to 2.

Life expectancy of greater than 3 months.

Patients must have normal organ and marrow function as defined below:

-absolute neutrophil count greater than or equal to 1,500/mcL

-platelets greater than or equal to 100,000/mcL

-hemoglobin greater than or equal to 10g/dL

-total bilirubin <= 1.5 X institutional upper limit of normal (<=3 x upper limit of normal in the presence of documented Gilbert s syndrome or liver metastases at baseline)

-AST(SGOT)/ALT(SGPT) less than or equal to 3 X institutional upper limit of normal

-creatinine <=1.5X institutional upper limit of normal OR

-creatinine clearance CrC1 greater than or equal to 60 mL/min/1.73m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73m^2.

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm (greater than or equal to 2 cm) by chest x-ray or as greater than or equal to 10 mm (greater than or equal to 1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.

Patients must have a tumor site amenable to biopsy, and this needs to be a lesion separate to those considered for RECIST measurable lesions.

The effects of talazoparib on the developing human fetus are unknown. For this reason and because PARP inhibitors are known to be teratogenic, women of child-bearing potential must agree to use a highly effective method of contraception for the duration of study participation and for at least 7 months after completing study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male patients with female partners of reproductive potential and pregnant partners who are treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation and for at least 4 months after completion of talazoparib administration

Patients must be able to swallow whole tablets or capsules. Nasogastric or G-tube administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed.

Ability to understand and the willingness to sign a written informed consent document.

Patients must have recurrent, locally advanced or metastatic disease

Patients must have progressed on or after at least one line of standard-of- care (SOC) intervention, except for those patients without SOC or for whom talazoparib is SOC


Patients with ovarian cancer

-All patients with ovarian cancer should have one prior platinum-based therapy.

-Patients with ovarian cancer with platinum-sensitive disease are eligible. Patients with platinum-refractory disease are not eligible.

-Patients with gBRCAm ovarian cancer must also have progressed on a PARP inhibitor. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented.

Patients with pancreatic cancer

-All patients with pancreatic cancer should have received prior platinum- containing therapy in the metastatic setting.

Patients with breast cancer

-Patients with HER2+ breast cancer should have had 2 prior systemic lines of therapy in the metastatic setting, including anti-HER2 therapy.

-Patients with breast cancer who are eligible for a PARP inhibitor by FDA approvals must have had prior PARP inhibitor as per FDA indication. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented.

Patients with gastric cancer

-Patients with HER2+ gastric cancer should have had received anti-HER2 therapy in the metastatic setting

Patients with prostate cancer

-Patients with prostate cancer who are eligible for a PARP inhibitor by FDA approvals must have had prior PARP inhibitor for eligibility. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented.

-All patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on prior therapy.

-Patients with castration resistant prostate cancer must have castrate levels of testosterone (less than 50 ng/dL [1.74 nmol/L].

-Patients with metastatic hormone-resistant (HR) prostate cancer and mutations in either BRCA1, BRCA2, or ATM should continue to receive anti-androgen receptor (anti-AR) therapy


Patients who have had chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter (6 weeks for nitrosoureas or mitomycin C)<TAB>Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study and be (Bullet) 1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events.

Patients who have had prior treatment with talazoparib are ineligible.

Patients who have had prior monoclonal antibody therapy must have completed that therapy greater than or equal to 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment) except for monoclonal antibody therapies that have been proven to be safe when combined with PARPi treatment (such as anti-PD-1/PD-L1 and anti- HER2), which must be completed greater than or equal to 4 weeks prior to enrollment.

Patients who are receiving any other investigational agents.

Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for greater than or equal to 1 month without requiring steroid and anti-seizure medication are eligible to participate

Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of talazoparib will be determined following review by the principal investigator.

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown.

HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded. Low-dose warfarin (less than or equal to 1 mg/day) is permitted.

Women who are currently lactating.

History of prior malignancies within the past 3 years other than non-melanomatous skin cancers that have been controlled.

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Murai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, Ji J, Takeda S, Pommier Y. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012 Nov 1;72(21):5588-99. doi: 10.1158/0008-5472.CAN-12-2753. PMID: 23118055; PMCID: PMC3528345.

Pommier Y, O'Connor MJ, de Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci Transl Med. 2016 Oct 26;8(362):362ps17. doi: 10.1126/scitranslmed.aaf9246. Erratum in: Sci Transl Med. 2016 Dec 7;8(368):368er7. PMID: 27797957.

Wilsker DF, Barrett AM, Dull AB, Lawrence SM, Hollingshead MG, Chen A, Kummar S, Parchment RE, Doroshow JH, Kinders RJ. Evaluation of Pharmacodynamic Responses to Cancer Therapeutic Agents Using DNA Damage Markers. Clin Cancer Res. 2019 May 15;25(10):3084-3095. doi: 10.1158/1078-0432.CCR-18-2523. Epub 2019 Feb 21. PMID: 30792217; PMCID: PMC6522288.

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Principal Investigator

Referral Contact

For more information:

Alice P. Chen, M.D.
National Cancer Institute (NCI)
(240) 781-3320

Jennifer H. Zlott
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 8D53
10 Center Drive
Bethesda, Maryland 20892
(240) 760-6046

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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