Talzenna (talazoparib) / Pfizer, BioMarin - LARVOL DELTA

PARP inhibitors and the rising incidence of secondary myelodysplastic syndrome and acute myeloid leukemia: A comprehensive meta-analysis (ASH 2025) - " The combined cohort included 106,793 patients treated with PARPi, including olaparib, niraparib, rucaparib, and talazoparib. This meta-analysis highlights that while MDS and AML are uncommon complications of PARP inhibitor therapy, their occurrence is clinically meaningful, with an overall incidence of approximately 1.5%. The risk notably increases with extended treatment duration and is associated with substantial mortality. These results underscore the importance of vigilant hematologic monitoring in patients receiving long-term PARP inhibitors and emphasize the need for prospective studies to discover predictive biomarkers and enhance personalized risk stratification."

Retrospective data • Acute Myelogenous Leukemia • Breast Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Ovarian Cancer • Solid Tumor • BRCA

Hematologic toxicities associated with PARP inhibitors: Real world pharmacovigilance updated study using faers database with era-trend evaluation and serious outcome modeling (ASH 2025) - "We employed 4 PARPi drugs (included generic and brand names),olaparib, niraparib, rucaparib, and talazoparib were coded as a primary suspect drug. This is the largest real-world study to date demonstrating specific hematologic AEs withPARPi. Our results show distinct and varying patterns of hematologic toxicity across PARPi, with thestrongest disproportionality observed for cytopenias, particularly thrombocytopenia, leukopenia, andanemia, and notable signals for MDS. Recognizing these patterns will help clinicians better monitor andmanage patients receiving PARPi therapy."

Adverse events • Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Breast Cancer • Leukopenia • Myelodysplastic Syndrome • Ovarian Cancer • Solid Tumor • Thrombocytopenia

PARP inhibition by talazoparib results in leukemia cell death via induction of myeloid differentiation (ASH 2025) - "Across multiple cell lines, talazoparibconsistently exhibited more potent dose dependent anti-proliferative effects on AML growth than otherPARP inhibitors (olaparib,niraparib, rucaparib). We demonstrate here that talazoparib exerts potent anti-tumor activity across an array ofhuman AML cell lines, patient samples, and an in vivo xenograft model in part due to induction ofmyeloid differentiation. This was characterized by attenuated growth, prominent morphological andmolecular hallmarks, and increased cell death. Our results suggest that talazoparib may represent anovel mutation-agnostic differentiation therapy for acute myeloid leukemia."

Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Leukemia • Ovarian Cancer • BRCA1 • BRCA2 • CD14 • CDK2 • IL1B • ITGAM

Identifying novel 'druggable' targets via Npm1A-turboid fusion and mass spectrometry to overcome genetic or adaptive resistance to menin inhibitors in mtNPM1 AML (ASH 2025) - "Treatment with revumenib may also cause emergenceof hot spot mutations in menin (e.g., S160T, M327V, M327I, G331D, G331R, and T349M) exhibitingreduced affinity to MI-binding...OCI-AML3 MEN1-M327I cells were resistant toSNDX-50469, ziftomenib, and DS1594b, but sensitive to the second-generation MI, bleximenib, aspreviously reported.To identify novel 'druggable' targets in mtNpm1 AML cells either sensitive or resistant to MI, we knockedin TurboID by CRISPR/Cas9 into the C-terminus of the mtNpm1 gene in OCI-AML3 cells...When combined with a BET inhibitor (pelabresib) ora novel dual BET/HAT inhibitor (NEO2734/EP31670), both RocA and talazoparib induced synergisticlethality in the sensitive OCI-AML3 and OCI-AML2-Npm1A KI, as well as the MI-resistant (OCI-AML3-Menin-M327I or the OCI-AML3 MITR) cells...Exvivo treatment with EP31670 and RocA or talazoparib induced synergistic loss of viability in MI (SNDX-50469)-resistant, patient-derived (N = 3) mtNpm1 AML cells. In the..."

IO biomarker • Acute Myelogenous Leukemia • AURKA • CDK9 • CDKN1A • EIF4A1 • EIF4A2 • FLT3 • HOXA9 • IL7R • IRAK4 • KMT2A • MEIS1 • MEN1 • MYC • NPM1 • PLK1 • S100A8 • SF3B1 • SMARCA2 • TP53

Safety and efficacy of PARP inhibitors in metastatic castration-resistant prostate cancer with DNA damage repair alterations: A systematic review and meta-analysis of randomized controlled trials (ESMO Asia 2025) - "Risk of bias was assessed with Cochrane RoB 2.0. Seven RCTs evaluating olaparib, niraparib, rucaparib, and talazoparib in DDR-altered mCRPC were included. PARP inhibitors significantly prolong rPFS and improve OS in DDR-altered mCRPC, especially in BRCA1/2-mutated disease. However, this comes with an increased risk of SAEs, particularly hematologic events. These findings underscore the importance of individualized risk–benefit assessment, close monitoring, and judicious use of PARP inhibitors in routine practice for biomarker-selected mCRPC patients."

Metastases • Retrospective data • Review • Acute Myelogenous Leukemia • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2

Talazoparib Formulation Bridging in Cancer Patients-Challenges and the Critical Role of Model-Informed Drug Development in Approval Despite Failed Bioequivalence. (PubMed, CPT Pharmacometrics Syst Pharmacol) - P1 | "MIDD was critical in study design optimization and supported approval of the SGC formulation. Trial Registration: ClinicalTrials.gov Identifier: NCT04672460."

Journal • Genito-urinary Cancer • Hematological Disorders • Oncology • Prostate Cancer • Solid Tumor

Poly (ADP-ribose) polymerase (PARP) inhibitors approved for the treatment of cancer. (PubMed, Pharmacol Res) - "The FDA has approved four PARP inhibitors (olaparib, rucaparib, niraparib, and talazoparib) for the treatment of ovarian, breast, prostate, and pancreatic cancer...The Chinese NMPA has approved three PARP antagonists (fuzuloparib, pamiparib, senaparib) for the treatment of ovarian cancer. All seven of these drugs are orally bioavailable and fall within the criteria of Lipinski's rule of five. Drug resistance develops in most PARP-inhibitor-treated cancer patients within one or two years."

Journal • Review • Breast Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD

Anticancer sensitivities and biological characteristics of HCT116 cells resistant to the selective poly(ADP-ribose) glycohydrolase inhibitor. (PubMed, FEBS Open Bio) - "Interestingly, HCT116RPDD cells exhibited greater sensitivity to γ-ray irradiation and the nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 than the parental HCT116 cells, yet showed comparable sensitivity to 5-FU, cisplatin, and PARP inhibitors olaparib, talazoparib, and veliparib. Furthermore, we observed that HCT116RPDD cells tended to maintain slightly higher levels of intracellular NAD+/NADH and ATP compared to parental HCT116 cells. These findings suggest that cancer cells employ a mechanism to regulate NAD+ and ATP levels, thereby avoiding cell death from intracellular PAR accumulation through coordinated PARP-PARG regulation."

Journal • Colorectal Cancer • Oncology • Solid Tumor • NAMPT

Parp inhibitors use in patients in germline palb2 or somatic brca1/2 mutations carriers with metastatic breast cancer: real life data from the esme database (SABCS 2025) - "In this multicenter real-life cohort of MBC patients with a sBRCA1/2 or a gPALB2 mutation, effectiveness of PARPi appeared in line with phase II trials. These data further support the use of olaparib or talazoparib in gPALB2m, and possibly in sBRCA1/2m."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • HER-2 • PALB2

Consideration of Off-Label Therapies as Appropriate Comparator Therapy in Early Benefit Assessments in Germany Under the ALBVVG Legislation (ISPOR-EU 2025) - "The G-BA decisions regarding the choice of ACT were analyzed with a focus on the reasoning provided in the supporting documents. The selected EBA procedures showed varying outcomes: For dupilumab (eosinophilic esophagitis), an established off-label therapy was considered appropriate based on evidence-based guidelines and extensive clinical experience. For midostaurin (systemic mastocytosis), avapritinib, cladribine, and imatinib were recognized as ACT despite not all being approved for the corresponding indication, acknowledging their established role in treatment algorithms. For lisocabtagene maraleucel (various B-cell lymphomas after prior therapy), off-label use was deemed appropriate, particularly considering the disease severity and limited therapeutic alternatives for these vulnerable patients. Conversely, for talazoparib (metastatic castration-resistant prostate carcinoma), the off-label use of abiraterone acetate with prednisone/prednisolone and enzalutamide was..."

B Cell Lymphoma • Castration-Resistant Prostate Cancer • Eosinophilic Esophagitis • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Prostate Cancer • Solid Tumor

Efficacy at a cost?-quality of life implications of PARP inhibition in the homologus recombination repair (HRR) cohort of TALAPRO-2. (PubMed, Transl Androl Urol) - No abstract available

HEOR • Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

DCMiC: a double-cylinder micro-chamber platform for high-throughput drug screening and modeling of microenvironmental resistance in Ewing sarcoma. (PubMed, Lab Chip) - "As a result, we identified Torin 2, talazoparib, and trabectedin as top 3 candidates with potent anti-Ewing sarcoma activity. Mechanistically, exogenous TGF-β1 was sufficient to induce resistance in tumor-only spheroids, whereas pharmacological inhibition of TGF-β1 signaling restored drug sensitivity in heterotypic spheroids. These findings establish the DCMiC platform as a low-cost, physiologically relevant system for modeling tumor-stroma interactions and enabling scalable drug discovery in clinically relevant contexts for Ewing sarcoma and other solid tumors."

Journal • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • TGFB1

Case Report: Deep and Durable Response to Talazoparib in Germline BRCA2-Mutated Rectal Neuroendocrine Carcinoma (Frontiers) - "A 55-year-old man with ongoing severe psoriatic arthritis presented with a two-week history of rectal pain, abdominal distention, and diarrhea...Biopsy of the rectal lesion demonstrated a high-grade, poorly differentiated NEC with a Ki-67 proliferation index of 99%....At 12.5 months from initial diagnosis, including after 7.5 months on talazoparib, the patient continues to show ongoing radiographic response with excellent tolerability and no adverse effects. This case illustrates the potential role of PARP inhibitors in the management of BRCA2-mutated high-grade rectal NEC."

Clinical • Neuroendocrine Carcinoma • Rectal Cancer • BRCA2

ONITT: Study of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma (clinicaltrials.gov) - P1/2 | N=90 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Active, not recruiting ➔ Recruiting | N=46 ➔ 90

Enrollment change • Enrollment open • Embryonal Tumor • Ewing Sarcoma • Germ Cell Tumors • Hepatoblastoma • Nephrology • Neuroblastoma • Oncology • Osteosarcoma • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • EWSR1 • FLI1

PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: Rationale, Mechanisms, and Clinical Applications. (PubMed, Eur Urol Oncol) - "Promising results have led to the approval of several PARPi agents as monotherapy or in combination with ARPIs in selected or unselected patients when chemotherapy is not clinically indicated. However, some questions remain regarding patient selection and treatment sequencing."

Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • PALB2

Combined DNA-PK and PARP Inhibition as a Therapeutic Strategy in BRCA-Mutated Prostate Cancer: An in Vitro Pilot Study. (PubMed, Technol Cancer Res Treat) - "Scramble LNCaP, BRCA1 KO, and BRCA2 KO cells were treated with the PARPi talazoparib, the DNA-PK inhibitor nedisertib and their combination. Therapeutically targeting NHEJ presents a promising approach in treating BRCA-mutated PCa. Further in vivo investigations are required to assess the tolerability of this drug combination."

Journal • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ANXA5 • BRCA • BRCA1 • BRCA2

Radiosensitization Effect of PARP Inhibitor Talazoparib Involves Decreasing Mitochondrial Membrane Potential and Induction of Cellular Senescence. (PubMed, Curr Issues Mol Biol) - "ER10 values for talazoparib, olaparib rucaparib, ABT888 and niraparib were 1.5, 1.8, 2.8, 1.4, and 1.4, respectively. When the p21 gene was knocked down, both the decrease in mitochondrial membrane potential and senescence level were attenuated, suggesting that p21 is involved in senescence induction after γ-irradiation combined with talazoparib treatment. Taken together, we showed that PARP inhibitor talazoparib treatment in combination with γ-irradiation causes cellular senescence in lung cancer cells, involving p21 function."

Journal • Lung Cancer • Oncology • Solid Tumor • CDKN1A

Matching-Adjusted Indirect Comparisons (MAICs) of Talazoparib Plus Enzalutamide (TALA+ENZA) versus Olaparib Plus Abiraterone Acetate (OLAP+AAP) for first-line (1L) therapy in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC): Unselected and Homologous Recombination Repair (HRR)-deficient populations (EMUC 2025) - P3 | "Conclusions These MAIC analyses suggest that TALA+ENZA is a beneficial 1L treatment option for unselected and HRR-deficient mCRPC. While weighting was used to align trial populations, residual imbalances may remain, and results should be interpreted considering these assumptions."

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

Computational Chemistry Advances in the Development of PARP1 Inhibitors for Breast Cancer Therapy. (PubMed, Pharmaceuticals (Basel)) - "Some of the most prominent examples are Olaparib (IC50 = 5 nM), Rucaparib (IC50 = 7 nM), and Talazoparib (IC50 = 1 nM), which were optimized with docking scores between -9.0 to -9.3 kcal/mol and validated by in vitro and in vivo assays, achieving 60-80% inhibition of tumor growth in BRCA-mutated models and achieving up to 21-month improvement in progression-free survival in clinical trials of BRCA-mutated breast and ovarian cancer patients. Employing computation and experimental verification in a hybrid strategy have brought next-generation inhibitors to the clinic with accelerated development, higher efficacy, and personalized treatment for breast cancer patients. Future approaches, including AI-aided generative models and multi-omics integration, have the promise to further refine inhibitor design, paving the way for precision oncology."

Journal • Review • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD

A Population-Specific PARP1 Gene Variation Modulates PARP Trapping. (PubMed, bioRxiv) - "Talazoparib switches from Type-II PARPi behavior in PARP1A762 to allosteric, pro-retention Type-I behavior for PARP1V762. Thus, both PARPi efficacy and dose-limiting tolerability depends on PARP1 allele, motivating variant-guided cancer therapies."

Journal • Oncology • HRD • PARP1 • XRCC1

Population Pharmacokinetics Analysis of Talazoparib and Enzalutamide Combination Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer. (PubMed, J Clin Pharmacol) - P3 | "The single covariate effect of baseline creatinine clearance on CLt0/Ft showed that relative to the reference value for normal renal function, CLt0/Ft decreased by 8% for mild, 27% for moderate, and 46.7% for severe renal impairment. Simulations showed that a dose reduction of enzalutamide does not require talazoparib dose modification since the magnitude of exposure reduction for talazoparib was not considered clinically significant."

Journal • PK/PD data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Disease • Solid Tumor • Urology • HRD

Exploratory analyses of homologous recombination repair alterations (HRRm) by gene subgroup and potential associations with efficacy in the HRR-deficient population from TALAPRO-2 (DGHO 2025) - P3 | "Background: In TALAPRO-2 (NCT03395197), talazoparib (TALA) + enzalutamide (ENZA) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) vs placebo (PBO) + ENZA in patients (pts) with mCRPC harboring HRRm assessed prospectively. An efficacy benefit was evident for TALA+ENZA vs PBO+ENZA across multiple mutational subgroups and was most pronounced for the BRCA1-PALB2-BRCA2 axis and CDK12, with benefit also for ATM. Analyses of additional efficacy endpoints will be presented."

Clinical • Castration-Resistant Prostate Cancer • Prostate Cancer • BRCA • BRCA1 • BRCA2 • CDK12 • HRD • PALB2

Indirect comparisons of efficacy outcomes between Talazoparib and Niraparib in combination with Androgen Receptor Pathway Inhibitors (ARPis) for first-line (1L) treatment in patients with Homologous Recombination Repair (HRR)-deficient and BRCA-mutated (BRCAm) metastatic Castration-Resistant Prostate Cancer (mCRPC) (EMUC 2025) - "While both talazoparib plus enzalutamide (TALA+ENZA) and niraparib plus abiraterone acetate (NIRA+AAP) have demonstrated efficacy in separate Phase 3 trials, direct comparisons are lacking. Bolded values are statistically significant. Conclusions These findings suggest that HRR-deficient and BRCAm mCRPC patients receiving TALA+ENZA may have greater clinical benefit over NIRA+AAP in the 1L setting."

Clinical • Combination therapy • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • HRD

Population Impact of Performing BRCA1/2 Testing to Guide Metastatic Castration-Resistant Prostate Cancer Treatment in Spain (ISPOR-EU 2025) - "Talazoparib (TALA), a PARPi, with enzalutamide (ENZ, an androgen-receptor pathway inhibitor [ARPi]) showed statistically significant benefit over ENZ in the TALAPRO-2 (TP-2) trial...This study assesses the clinical impact of BRCA1/2 testing for newly diagnosed patients with mCRPC in Spain. Two testing strategies were analysed: no testing (patients received ENZ, abiraterone [ABI] or docetaxel [DOC]); and universal BRCA1/2 testing, where BRCAm patients received TALA with ENZ and non-BRCAm received either ENZ, ABI or DOC... Universal BRCA1/2 testing would result in substantial population-level clinical benefits for mCRPC patients in Spain. Increased testing is needed to ensure access to targeted treatment with PARPi."

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD

The effect of talazoparib in combination with radiation and enzalutamide in prostate cancer cell models (EMUC 2025) - "In both cell lines, the triple combination therapy produced the highest apoptotic rates. However, only marginally greater than dual therapies, which were clearly more effective than monotherapies."

Combination therapy • Tumor mutational burden • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • ANXA5 • AR • BRCA1 • BRCA2 • TMB