Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Therapy Name | Talazoparib |
Synonyms | |
Therapy Description |
Talzenna (talazoparib) is an inhibitor of PARP1 and PARP2, which prevents the DNA repair of single strand DNA breaks, thus causing the accumulation of DNA strand breaks, genomic instability and apoptosis, and leads to lethality in homologous recombination repair deficient cells (PMID: 28242752). Talzenna (talazoparib) is FDA approved for use in patients with ERBB2 (HER2)-negative breast cancer harboring deleterious or suspected deleterious germline BRCA mutations, and in combination with Xtandi (enzalutamide) in patients with homologous recombination repair gene (ATM, ATR, BRCA1/2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C)-mutated metastatic castration-resistant prostate cancer (FDA.gov). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Talazoparib | Talzenna | BMN673 | PARP Inhibitor (Pan) 30 | Talzenna (talazoparib) is an inhibitor of PARP1 and PARP2, which prevents the DNA repair of single strand DNA breaks, thus causing the accumulation of DNA strand breaks, genomic instability and apoptosis, and leads to lethality in homologous recombination repair deficient cells (PMID: 28242752). Talzenna (talazoparib) is FDA approved for use in patients with ERBB2 (HER2)-negative breast cancer harboring deleterious or suspected deleterious germline BRCA mutations, and in combination with Xtandi (enzalutamide) in patients with homologous recombination repair gene (ATM, ATR, BRCA1/2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C)-mutated metastatic castration-resistant prostate cancer (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
IDH1 R132H | colorectal cancer | predicted - sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring IDH1 R132H were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
PALB2 mutant | pancreatic cancer | predicted - sensitive | Talazoparib | Case Reports/Case Series | Actionable | In a Phase I trial, Talzenna (talazoparib) treatment resulted in an objective response rate of 20.0% (2/10, 2 partial responses) and a clinical benefit rate of 30.0% in patients with pancreatic cancer, including a partial response in one patient harboring a PALB2 mutation (PMID: 28242752; NCT01286987). | 28242752 |
IDH2 mutant | acute myeloid leukemia | predicted - sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH2 mutation were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
IDH1 R132H | Advanced Solid Tumor | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
TET2 loss | acute myeloid leukemia | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) decreased colony formation in mouse acute myeloid leukemia cells harboring TET2 loss along with a FLT3-ITD mutation in culture (PMID: 34215619). | 34215619 |
RAD51D S207L | Advanced Solid Tumor | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing RAD51D S207L demonstrated decreased survival when treated with Talzenna (talazoparib) in culture (PMID: 28646019). | 28646019 |
ARID1A Q456* | colorectal cancer | sensitive | Talazoparib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Talzenna (talazoparib) inhibited colony formation and proliferation of a human colorectal cancer cell line harboring ARID1A Q456* in culture and inhibited tumor formation in colorectal cancer xenografts harboring ARID1A Q456* (PMID: 26069190). | 26069190 |
PALB2 inact mut | Her2-receptor negative breast cancer | predicted - sensitive | Talazoparib | Case Reports/Case Series | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment was well tolerated, and among 12 evaluable ERBB2 (HER2)-negative breast cancer patients with a homologous repair pathway mutation resulted in response in 25% (3/12) of patients, including two patients with germline mutations in PALB2, and resulted in stable disease for >/= 6 months in 3 patients, including one patient with a germline PALB2 mutation (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3006). | detail... |
CHEK2 inact mut FANCA inact mut PTEN inact mut | Her2-receptor negative breast cancer | predicted - sensitive | Talazoparib | Case Reports/Case Series | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment was well tolerated, and among 12 evaluable ERBB2 (HER2)-negative breast cancer patients with a homologous repair pathway mutation resulted in response in 25% (3/12) of patients, including a patient with germline mutations in CHEK2 and FANCA, and a somatic PTEN mutation (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3006). | detail... |
IDH1 R132C | high grade glioma | sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived glioma cells harboring IDH1 R132C demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
PTEN Y336* | breast cancer | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells expressing PTEN Y336* demonstrated increased sensitivity to Talzenna (talazoparib) compared to cells expressing wild-type Pten in culture (PMID: 25946202}. | 25946202 |
BRAF V600E NRAS Q61K | melanoma | sensitive | Talazoparib | Preclinical - Pdx | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited tumor growth and led to improved survival compared to controls in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61K (PMID: 37729428). | 37729428 |
ARID1A dec exp | breast cancer | conflicting | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, human mammary epithelial cells with knockdown of ARID1A demonstrated resistance to Talzenna (talazoparib) when compared to parental cells in culture (PMID: 29669295). | 29669295 |
ARID1A dec exp | breast cancer | conflicting | Talazoparib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Talzenna (talazoparib) selectively inhibited growth and induced apoptosis in breast cancer cells with knock-down of ARID1A in culture, and inhibited tumor growth in ARID1A-deficient breast cancer cell line xenograft models (PMID: 26069190). | 26069190 |
ARID1A dec exp | ovarian cancer | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, knockdown of ARID1A resulted in increased sensitivity to Talzenna (talazoparib) in ovarian cancer cells in culture (PMID: 26069190). | 26069190 |
PTEN mutant | Advanced Solid Tumor | no benefit | Talazoparib | Phase II | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment did not result in significant clinical benefit in patients with advanced solid tumors harboring PTEN mutation or loss (by IHC), with one patient harboring a PTEN mutation achieved a prolonged stable disease as best response in a cohort of 13 patients (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A096; NCT02286687). | detail... |
RAD51C H192_R193delinsGG | ovarian carcinoma | resistant | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, ovarian carcinoma cells expressing RAD51C H192_R193delinsGG demonstrated resistance to Talzenna (talazoparib) in culture (PMID: 28588062). | 28588062 |
ATRX loss IDH1 R132H | high grade glioma | predicted - sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited viability of immortalized astrocytes expressing IDH1 R132H with loss of ATRX in culture (PMID: 34118569). | 34118569 |
RAD51C R193W | ovarian carcinoma | resistant | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, ovarian carcinoma cells expressing RAD51C R193W demonstrated resistance to Talzenna (talazoparib) in culture (PMID: 28588062). | 28588062 |
PTEN negative | Advanced Solid Tumor | conflicting | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, PTEN-deficient cancer cell lines with DNA repair deficiency demonstrated high sensitivity to the PARP inhibitor Talzenna (talazoparib) (PMID: 23881923). | 23881923 |
PTEN negative | Advanced Solid Tumor | conflicting | Talazoparib | Phase II | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment did not result in significant clinical benefit in patients with advanced solid tumors harboring PTEN mutation or loss (by IHC), with one patient harboring a PTEN mutation achieved a prolonged stable disease as best response in a cohort of 13 patients (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A096; NCT02286687). | detail... |
ATRX loss | high grade glioma | predicted - sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited viability of immortalized astrocytes with loss of ATRX in culture (PMID: 34118569). | 34118569 |
DNMT3A loss | acute myeloid leukemia | resistant | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, mouse acute myeloid leukmia cells harboring DNMT3A loss along with a FLT3-ITD mutation were resistant to Talzenna (talazoparib) in culture (PMID: 34215619). | 34215619 |
PALB2 Y1108fs | nephroblastoma | sensitive | Talazoparib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a Wilms tumor cell line and xenograft model harboring PALB2 Y1108fs demonstrated a complete response to Talzenna (talazoparib) (PMID: 25263539). | 25263539 |
ATM dec exp | breast cancer | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, knockdown of ATM expression sensitized breast cancer cells to treatment with Talzenna (talazoparib) in culture (PMID: 23881923). | 23881923 |
RAD51C R193L | ovarian carcinoma | resistant | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, ovarian carcinoma cells expressing RAD51C R193L demonstrated resistance to Talzenna (talazoparib) in culture (PMID: 28588062). | 28588062 |
IDH1 R132H | colon carcinoma | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, colon carcinoma cells over expressing IDH1 R132H demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
DNMT3A loss TET2 loss | acute myeloid leukemia | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) decreased colony formation in murine acute myeloid leukemia cells harboring TET2 and DNMT3A loss along with a FLT3-ITD mutation in culture (PMID: 34215619). | 34215619 |
BRAF V600E NRAS Q61R | melanoma | sensitive | Talazoparib | Preclinical - Pdx | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited tumor growth and led to improved survival compared to controls in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61R (PMID: 37729428). | 37729428 |
IDH1 mutant | acute myeloid leukemia | predicted - sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH1 mutation were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
PALB2 inact mut | estrogen-receptor positive breast cancer | sensitive | Talazoparib | Guideline | Actionable | Talzenna (talazoparib) is included in guidelines as second-line therapy for patients with ESR1 (ER)-positive, ERBB2 (HER2)-negative metastatic breast cancer with germline or somatic pathogenic/likely pathogenic PALB2 mutations who have progressed on an endocrine therapy plus CDK4/6 inhibitor (PMID: 34678411; ESMO.org). | 34678411 detail... |
IDH1 R132H | high grade glioma | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited viability of immortalized astrocytes expressing IDH1 R132H in culture (PMID: 34118569). | 34118569 |
IDH1 R132H | high grade glioma | sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived glioma cells harboring IDH1 R132H demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02997163 | Phase I | Talazoparib | An Open-Label Pharmacokinetics and Safety Study of Talazoparib | Completed | USA | CAN | 0 |
NCT03148795 | Phase II | Talazoparib | A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer | Completed | USA | NLD | ITA | GBR | FRA | ESP | DEU | BEL | AUT | AUS | 4 |
NCT03974217 | Phase I | Talazoparib | Talazoparib for Cohesin-Mutated AML and MDS With Excess Blasts | Recruiting | USA | 0 |
NCT04801966 | Phase 0 | Palbociclib Alpelisib Atezolizumab Vemurafenib Ribociclib Talazoparib Cobimetinib Trametinib Abemaciclib Dabrafenib Nivolumab Binimetinib Pembrolizumab Encorafenib | Safety and Oversight of the Individually Tailored Treatment Approach: A Novel Pilot Study (TAILOR) | Terminated | AUS | 0 |
NCT02693535 | Phase II | Cobimetinib + Vemurafenib Atezolizumab + Talazoparib Regorafenib Larotrectinib Trastuzumab + Tucatinib Ipilimumab + Nivolumab Palbociclib Afatinib Entrectinib Talazoparib Pembrolizumab Temsirolimus Pertuzumab + Trastuzumab Atezolizumab + Pertuzumab/trastuzumab/hyaluronidase-zzxf Crizotinib Abemaciclib Sunitinib Olaparib | TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (TAPUR) | Recruiting | USA | 0 |
NCT03964532 | Phase Ib/II | Talazoparib Avelumab + Talazoparib | TALAVE: Induction Talazoparib Followed by Combination of Talazoparib and Avelumab in Advanced Breast Cancer | Active, not recruiting | USA | 0 |
NCT03968406 | Phase I | Talazoparib | Talazoparib and Radiation Therapy in Treating Patients With Locally Recurrent Gynecologic Cancers | Recruiting | USA | 0 |
NCT04550494 | Phase II | Talazoparib | Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations | Recruiting | USA | 0 |
NCT02925234 | Phase II | Palbociclib Ribociclib Lenvatinib Ipilimumab + Nivolumab Trametinib Crizotinib Niraparib Selpercatinib Olaparib Erlotinib Erdafitinib Dabrafenib Dacomitinib Rucaparib Axitinib Panitumumab Pemigatinib Durvalumab Afatinib Entrectinib Tepotinib Alpelisib Atezolizumab + Bevacizumab Alectinib Regorafenib Cobimetinib + Vemurafenib Nilotinib Vismodegib Abemaciclib Sunitinib Nivolumab Cabozantinib Lorlatinib Talazoparib Dabrafenib + Trametinib Pembrolizumab Pertuzumab + Trastuzumab | The Drug Rediscovery Protocol (DRUP Trial) (DRUP) | Recruiting | NLD | 0 |
NCT02286687 | Phase II | Talazoparib | Talazoparib in Treating Patients With Recurrent, Refractory, Advanced, or Metastatic Cancers and Alterations in the BRCA Genes | Active, not recruiting | USA | 0 |
NCT02326844 | Phase II | Talazoparib | BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment | Terminated | USA | 0 |
NCT02154490 | Phase II | Docetaxel Nivolumab Palbociclib Durvalumab Ipilimumab + Nivolumab AZD4547 Taselisib Durvalumab + Tremelimumab Erlotinib + Rilotumumab Talazoparib Erlotinib | Lung-MAP: Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer | Completed | USA | CAN | 0 |
NCT02567396 | Phase I | Talazoparib | Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction | Withdrawn | 0 | |
NCT01286987 | Phase I | Talazoparib | Study of BMN 673, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors | Completed | USA | GBR | 0 |
NCT04462809 | Phase II | Talazoparib | Efficacy of a Maintenance Treatment With TALAzoparib Following First Line Platinum-based Chemotherapy in Malignant MESOthelioma (TALAMESO) | Not yet recruiting | 0 | |
NCT04170946 | Phase I | Talazoparib | Talazoparib and Thoracic RT for ES-SCLC | Recruiting | CAN | 0 |
NCT02921919 | Phase II | Talazoparib | Open-Label Extension and Safety Study of Talazoparib | Completed | USA | GBR | FRA | DEU | CAN | 4 |
NCT04756765 | Phase II | Talazoparib | Talazoparib Monotherapy in PALB2 Mutation Associated Advanced Breast Cancer | Recruiting | USA | 0 |
NCT02997176 | Phase I | Talazoparib | An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800) | Completed | USA | 0 |
NCT03990896 | Phase II | Talazoparib | Evaluation of Talazoparib, a PARP Inhibitor, in Patients With Somatic BRCA Mutant Metastatic Breast Cancer: Genotyping Based Clinical Trial | Recruiting | USA | 0 |
NCT05097599 | Phase II | Binimetinib + Encorafenib Trastuzumab deruxtecan Enfortumab vedotin-ejfv Talazoparib Lorlatinib | Strata PATH (Precision Indications for Approved Therapies) (Strata PATH) | Recruiting | USA | 0 |
NCT05898399 | Phase Ib/II | Olaparib ART6043 Talazoparib ART6043 + Olaparib ART6043 + Talazoparib | Study of ART6043 in Advanced/Metastatic Solid Tumors Patients | Recruiting | USA | 0 |
NCT04598321 | Phase I | Talazoparib | BrUOG 390: Neoadjuvant Treatment With Talazoparib | Terminated | USA | 0 |
NCT06193525 | Phase II | Talazoparib | FUnctional Selection of Advanced Breast Cancer Patients for Talazoparib Treatment Using the REpair Capacity (RECAP) Test (FUTURE) | Recruiting | NLD | 0 |
NCT03042910 | Phase I | Talazoparib | A Study to Assess the Effects of Talazoparib on Cardiac Repolarization in Patients With Advanced Solid Tumors | Completed | USA | 0 |
NCT02401347 | Phase II | Talazoparib | Phase II Trial of Talazoparib in BRCA1/2 Wild-type HER2-negative Breast Cancer and Other Solid Tumors | Completed | USA | 0 |
NCT04672460 | Phase I | Talazoparib | A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors | Completed | USA | AUS | 0 |
NCT02282345 | Phase II | Talazoparib | Talazoparib Before Standard Therapy in Treating Patients With Invasive, BRCA-Mutated Breast Cancer | Completed | USA | 0 |
NCT02537561 | Phase I | Talazoparib Cisplatin + Gemcitabine | Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors | Withdrawn | 0 | |
NCT01945775 | Phase III | Gemcitabine Capecitabine Vinorelbine Talazoparib Eribulin | A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study) (EMBRACA) | Completed | USA | ITA | GBR | FRA | ESP | DEU | BEL | AUS | 8 |
NCT03395197 | Phase III | Talazoparib | Talazoparib + NHT vs. NHT Monotherapy in DDR+ mCRPC (TALAPRO-2) | Active, not recruiting | USA | NZL | ITA | GBR | FRA | ESP | DEU | CAN | BEL | AUS | 16 |
NCT03377556 | Phase II | Talazoparib | Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer | Completed | USA | CAN | 0 |
NCT02034916 | Phase II | Talazoparib | A Phase 2, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673), in Locally Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (ABRAZO Study) | Terminated | USA | GBR | FRA | ESP | DEU | 0 |
NCT01989546 | Phase Ib/II | Talazoparib | Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations | Completed | USA | 0 |
NCT02316834 | Phase I | Talazoparib | POSITION: A PilOt Study of InducTion PARP InhibitiON in Ovarian Cancer | Completed | USA | 0 |
NCT03499353 | Phase II | Talazoparib | Talazoparib For Neoadjuvant Treatment Of Germline BRCA1/2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer | Terminated | USA | 0 |