Talzenna (talazoparib) / Pfizer, BioMarin - LARVOL DELTA

First-line talazoparib plus enzalutamide versus placebo plus enzalutamide for metastatic castration-resistant prostate cancer: patient-reported outcomes from the randomised, double-blind, placebo-controlled, phase 3 TALAPRO-2 trial. (PubMed, Lancet Oncol) - P3 | "Talazoparib plus enzalutamide prolonged time to definitive deterioration in GHS/QoL versus placebo plus enzalutamide. Together with clinical efficacy and safety data, these results inform the risk-benefit assessment of talazoparib plus enzalutamide in patients with metastatic castration-resistant prostate cancer in TALAPRO-2."

Clinical • Journal • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor • HRD

Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line (1L) treatment in patients (pts) with homologous recombination repair (HRR)-deficient metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. (ASCO-GU 2025) - P3 | " Pts with HRR-deficient tumors were randomized 1:1 to ENZA 160 mg + either TALA 0.5 mg (0.35 mg if moderate renal impairment) or PBO once daily and stratified by prior abiraterone or docetaxel (yes/no) for castration-sensitive PC. TALA + ENZA demonstrated a statistically significant and clinically meaningful improvement in OS vs ENZA. These data establish TALA + ENZA as a standard of care for 1L treatment in pts with HRR-deficient mCRPC. rPFS continued to favor TALA + ENZA."

Clinical • Late-breaking abstract • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • 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. (ASCO 2025) - P3 | "Funded by Pfizer Clinical Trial Registration Number: NCT03395197 Background: In TALAPRO-2, talazoparib (TALA) + enzalutamide (ENZA) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) vs ENZA + placebo (PBO) in patients (pts) with mCRPC harboring HRRm assessed prospectively. An efficacy benefit was evident for TALA + ENZA vs PBO + ENZA across multiple mutational subgroups assessed by gene, and was most pronounced for the BRCA1-PALB2-BRCA2 axis and CDK12, with benefit also apparent for ATM. Analyses of additional efficacy endpoints are planned and will be presented."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • CDK12 • HRD • PALB2

Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. (ASCO-GU 2025) - P3 | " In cohort 1, pts were randomized 1:1 to ENZA 160 mg + either TALA 0.5 mg (0.35 mg if moderate renal impairment) or PBO once daily and stratified by prior abiraterone or docetaxel (yes/no) for castration-sensitive PC and HRR gene alteration status. TALA + ENZA demonstrated a statistically significant and clinically meaningful improvement in OS vs standard-of-care ENZA as 1L treatment in pts with mCRPC unselected for HRR gene alterations. rPFS continued to favor TALA + ENZA. No new safety signals were identified with extended follow-up."

Clinical • Late-breaking abstract • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD

TALZENNA Plus XTANDI Significantly Improves Radiographic Progression-Free Survival in Metastatic Prostate Cancer (Businesswire) - "The study met its primary endpoint, with TALZENNA plus XTANDI demonstrating a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS), compared to placebo plus XTANDI. The results markedly exceeded the pre-specified target hazard ratio of 0.63, with the majority of patients remaining progression-free at the time of analysis....The TALAPRO-3 results will be submitted for presentation at an upcoming medical congress and will be discussed with global health authorities for potential regulatory submissions."

P3 data • Hormone Sensitive Prostate Cancer

Real-world effectiveness of systemic therapies after 177Lu]Lu-PSMA-617 (177Lu-PSMA-617) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC): A prostate cancer disease observation (PRECISION) data platform analysis. (ASCO-GU 2026) - "Systemic therapies included ARPIs (abiraterone, enzalutamide, darolutamide, apalutamide); chemotherapy (cabazitaxel, docetaxel, carboplatin, cisplatin, etoposide, mitoxantrone); immunotherapy (pembrolizumab, sipuleucel-T); poly (ADP-ribose) polymerase (PARP) inhibitors (niraparib, olaparib, talazoparib, rucaparib); and radium-223. In this real-world analysis, meaningful clinical responses were observed in a subset of patients who received subsequent systemic therapies after 177Lu-PSMA-617."

Clinical • Metastases • Real-world • Real-world effectiveness • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Acquired saruparib (AZD5305) resistance in BRCA1-deficient triple negative breast cancer is vulnerable to DNA damage response-targeted therapeutics (AACR 2026) - "SR cell lines exhibit altered inhibition of cellular PARP activity and PARP trapping in response to saruparib and the nonspecific PARPi talazoparib. Importantly, despite acquired saruparib resistance, SR cell lines retain sensitivity to other DNA damage response targeted therapeutics. Collectively, this work characterizes what we believe to be the first BRCA1-deficient models of acquired saruparib resistance and uncovers vulnerabilities that may inform rational combination strategies and novel therapeutic approaches for patients who progress on saruparib in the clinic."

Breast Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2

Establishment and characterisation of PDTOs and CAFs for the development of a co-culture system in pancreatic periampullary adenocarcinoma (AACR 2026) - "Drug screening of PDTOs with talazoparib and olaparib was conducted to examine the correlation between an HRD mutation and sensitivity to PARP inhibitors.4 PDTOs and 4 CAFs were successfully derived and cultured from PAC specimens. Building on this, defined CAF heterogeneity will be assessed for its association with immunosuppressive versus immunostimulatory profiles, and T cells, along with immunotherapeutic agents, will be incorporated into the co-cultures. These models will provide valuable insights into PAC tumour-stroma-immune biology and form the basis for advanced co-cultures to test strategies targeting the TME."

IO biomarker • Ampulla of Vater Adenocarcinoma • Oncology • Pancreatic Cancer • Solid Tumor • ACTA2 • ATM • CAFs • CD74 • COL1A1 • CTGF • CXCL1 • HRD • POSTN • VIM

Spatially resolved multi-omic profiling reveals BRCA-dependent immune remodeling during PARP inhibition and PD-L1 blockade (AACR 2026) - P1/2 | "The TALAVE study (NCT03964532) examined the combination of the PARPi (talazoparib) with PD-L1 blockade (avelumab). PD-1+ T cells localized to PD-L1-negative neighborhoods, and PD-L1+ tumor/myeloid cells were rapidly lost or confined to dying, immune-excluded regions, limiting the impact of PD-L1 blockade. Although PARPi re-engaged T cell programs in BRCA-MUT tumors, strategies beyond PD-L1 inhibition will be required to further enhance T cell infiltration and activation."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2 • CD163 • CD4 • CD68 • CD8 • HER-2

Comprehensive analysis of genomic landscape of ultra-rare pediatric malignant rhabdoid tumors (AACR 2026) - "This work builds on our previous studies investigating the in-vivo activity of the combination of the PARP1 inhibitor, PEGylated talazoparib (PEG~TLZ), and the DNA alkalyating agent, temozolomide (TMZ), in MRTs, as well as the associated transcriptional changes underlying therapeutic response. Overall, our comprehensive multi-omics characterization of these ultra-rare MRTs establishes a foundational and enduring resource for the pediatric cancer research community. By providing deeply annotated genomic, transcriptomic, and epigenomic profiles across diverse MRT subtypes, this dataset will support long-term mechanistic studies, enable identification of therapeutic vulnerabilities, and help guide the development of future clinical strategies for this highly aggressive pediatric cancer."

Clinical • Oncology • Rhabdoid Tumor • Sarcoma • BRCA1 • BRCA2 • SMARCB1 • TP53

Characterization of a panel of PDX models derived from PARP inhibitors pretreated breast and ovarian cancer patients for therapeutic evaluation (AACR 2026) - "To better recapitulate clinical resistance and advance precision therapy development, we established a panel of patient‑derived xenograft (PDX) models from PARP inhibitors pretreated breast and ovarian cancers, providing a translational platform to investigate resistance mechanisms and assess novel treatment strategies. Ten PDX models from patients pretreated with PARP inhibitors (Olaparib, Niraparib ± Bevacizumab), and Talazoparib + Avelumab) were established subcutaneously in immunodeficient mice (NOD.SCID, BALB/c nude, NSG-like) and characterized by histology and RNA sequencing. By developing this panel of clinically PARP inhibitor pretreated PDX models, we established a translational platform that reflects clinical disease progression. These models enable investigation of resistance mechanisms and evaluation of next-generation therapies and combinations, supporting preclinical decision-making."

Clinical • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD • MDM2 • MDM4 • PALB2 • TP53

Efficacy of DNA methyltransferase inhibition in combination with immune-checkpoint/PARP-inhibitor in colorectal cancer preclinical model (AACR 2026) - "In this study, we evaluated the therapeutic potential of epigenetic modulation using DNMT inhibitor 5-AZA-2ʹ-deoxycytidine (5AZA) in combination with immune-checkpoint inhibitor (ICI) anti-PD1 or PARP inhibitor BMN673 in syngeneic CRC mouse model.Methods...Notably, both combination groups showed significant downregulation of Hba and Hbb genes which encode the hemoglobin subunits, suggesting increased reactive oxygen species and associated apoptosis in tumors as a countereffect to the observed upregulation of Tuba3a, Tuba3b and Trap1a genes all associated with hypoxia in both combination groups.Conclusion. Our findings suggest that administration of DNMT inhibitors in combination with ICI or PARP inhibitors could be a promising strategy to substantially improve the treatment and survival outcomes in CRC."

Combination therapy • IO biomarker • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • HBB • IL10 • IL1B • IL2 • TNFA

DNMTi in combination with PARPi inhibits aberrant Wnt/β-catenin signaling and tenasin-C pathways, cancer stemness and metastasis in triple negative breast cancer (AACR 2026) - "Genome-wide transcriptomic analysis in TNBC cell line MDA MB 231 demonstrated that combining DNMTis azacytidine (AZA) and PARPis talazoparib (TAL) down-regulated cancer stemness and metastases pathways, and key leading-edge genes including those involved in Wnt/β-catenin signaling and tenasin-C (TNC), a multimodular glycoprotein that promotes the migration of cancer cells, were decreased. Notably, we show for the first time in TNBC that Beta-catenin/TCF12 transcriptionally regulates TNC by binding to its promoter region and that inhibition or KD of WNT/Beta catenin or TNC expression decreases the cell migration, metastasis and stemness, mimicking the effects of the drug combination in TNBC cells. Taken together, our results show for the first time that PARPi and DNMTi combination therapy targets WNT/Beta-catenin signaling and TNC regulation in driving aggressive disease, metastasis, stemness and poor survival in TNBC."

Combination therapy • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALDH1A1 • BRCA • BRCA1 • BRCA2 • SOX2 • TCF12

A combination of PG3 and PARP inhibitors exhibits antitumor effects in both BRCA1-mutated and BRCA1-wild-type TNBC (AACR 2026) - "Hence, we hypothesized that PG3 can sensitize PRAP-resistant tumor cells (both BRCA1-mutant and wild-type) to PARP inhibitors by downregulating RAD51.The combination treatments of PG3 and Olaparib/Talazoparib showed synergistic inhibitory effects on triple-negative breast cancer cells, BRCA1-mutated SUM149 and MD-MB-436, and BRCA1-wildtype MD-MB-231 and MD-MB-468. PG3 blocked the olaparib-induced upregulation of RAD51 in SUM149cells, and the upregulation of BRCA1 and RAD51 in MD-MB231 cells. The combined treatment induced more DNA damage than olaparib or PG3 alone in SUM149 and MB231 cells, as indicated by increased γH2AX level."

Brain Cancer • Breast Cancer • Glioblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • E2F1 • FOXM1 • HRD • MYC • RAD51

Antitumor activity of PARP inhibitors in combination with Temozolomide in fumarate hydratase-deficient RCC (AACR 2026) - "The antitumor activity of two PARP inhibitors, Talazoparib and Niraparib, either as single agents or in combination with the alkylating chemotherapy agent temozolomide, was evaluated in several patient-derived HLRCC cell lines. Additional in vitro and in vivo studies are ongoing to further define the activity of these combinations and to better understand the underlying molecular mechanisms. This study highlights the potential therapeutic utility of PARP inhibitor-based combinations in targeting DNA repair defects in HLRCC and provides the impetus for further exploration of this strategy."

Combination therapy • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • FH • H2AX

Uncovering mechanisms of PARP inhibitor resistance in IDH1-mutant cancers via serial tumor transplantation and genome wide CRISPR-Cas9 knockout screen (AACR 2026) - "To investigate potential mechanisms by which PARPi resistance might arise, we first modeled PARPi-resistance in IDH1-mutant tumors via serial transplantation of patient-derived xenografts in mice treated with the PARPi talazoparib...To overcome this resistance, we found that treatment with the receptor tyrosine kinase inhibitor, cediranib, previously reported to suppress expression of downstream HDR factors, resensitizes these PARPi-resistant cells to PARPi treatment. As a next step, a genome wide CRISPR-Cas9 knockout screen is underway to uncover undescribed mechanisms PARPi resistance in IDH-mutant tumors. Our findings identify key pathways driving PARPi resistance in IDH1-mutant cancers and highlight potential therapeutic strategies to overcome this resistance."

Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • IDH1 • IDH2 • RIF1 • TP53BP1

Expanding the therapeutic window of PARP inhibitors by co-administering PARG inhibitors (AACR 2026) - "To address these limitations and expand the therapeutic window of PARPi, we investigated co-administration with selective PARG inhibitors (PARGi).Cell survival assays were used to evaluate the interaction between potent PARP inhibitors (talazoparib, saruparib), less potent PARP inhibitors (niraparib, olaparib, rucaparib), and selective PARG inhibitors in HR-deficient cell lines. PARG inhibition selectively mitigates PARPi-induced toxicity without compromising anticancer efficacy in HR-deficient tumors, thereby expanding the therapeutic window. This approach enables higher PARPi dosing for improved tumor control or equivalent efficacy with fewer adverse events, particularly anemia. By reducing PARPi-associated toxicity, PARG inhibition may also facilitate combination therapies, warranting further investigation."

Oncology • BRCA2

The PARP1-selective inhibitor and trapper saruparib achieves extended PARP1 target engagement in vitro, in vivo and in the clinic (AACR 2026) - P1/2 | "Multiple intermittent schedules of saruparib, compared to olaparib or talazoparib were evaluated in the BRCA1m-MDA-MB-436 model. These data suggest that short-term dose interruptions are unlikely to result in reduced efficacy, in contrast to approve non-selective PARPi where dose interruptions have been shown to reduce efficacy. These data also suggest that intermittent scheduling may be effective for saruparib in circumstances where minimising exposure may provide an optimal risk-benefit - for example cancer prevention."

Preclinical • Oncology • BRCA1

Single cell multiomics reveals evolutionary and epigenomic trajectories of PARP inhibitor resistance in BRCA mutant TNBC (AACR 2026) - "To dissect the mechanisms enabling tumor persistence, we performed integrated single-cell transcriptomic and chromatin-accessibility profiling on paired pre- and post-treatment patient-derived xenograft (PDX) samples from a Phase II trial of single-agent talazoparib in germline BRCA1/2-mutant TNBC...Collectively, our findings delineate the evolutionary routes by which BRCA-mutant TNBC evades PARP inhibition and highlight how both baseline HRR-proficient subpopulations and transcription factor driven chromatin reprogramming shape therapeutic outcome. These insights nominate actionable vulnerabilities that may be exploited to prevent or overcome resistance and enhance the durability of PARP-inhibitor therapy."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2

KBD111 is a highly selective, long-acting and brain-penetrant PARP1 inhibitor (AACR 2026) - "Background: Currently, several pan-PARP inhibitors such as olaparib, niraparib, and rucaparib are approved for the treatment of cancers with homologous recombination deficiency (HRD)...In addition, hematological toxicity was evaluated in vitro in CD34+ hematopoietic stem cells and in vivo in rats. KBD111 exhibited over 5,000-fold selectivity for PARP2 by DNA-trapping assays, demonstrated potent anti-proliferative activity against BRCA-mutant cancer cell lines, while showing markedly reduced cytotoxicity toward normal CD34⁺ hematopoietic stem cells (IC₅₀ >10,000 nM) compared to talazoparib (IC₅₀ = 27 nM)...Furthermore, KBD111 achieved superior tumor growth inhibition compared to AZD5305 in DLD-1 BRCA2⁻/⁻ xenograft models following once every two weeks oral dosing. In an intracranial MDA-MB-436-luc model, KBD111 also demonstrated enhanced efficacy relative to AZD9574 under QW oral dosing... KBD111 is a highly potent, long-acting and brain-penetrant PARP1 inhibitor with..."

Oncology • BRCA • BRCA2 • CD34 • HRD • PARP2

Study to Evaluate Sacituzumab Govitecan in Combination With Talazoparib in Patients With Metastatic Breast Cancer. (clinicaltrials.gov) - P1/2 | N=75 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2025 ➔ Jun 2026

Enrollment closed • Trial primary completion date • Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Molecular testing in breast cancer: The key to more personalized and effective therapies (DKK 2026) - P2, P4 | "Clinical Relevance: For pts with hereditary BRCA1/2 mutations, studies such as OlympiA, OlympiAD, and EMBRACA have demonstrated significant benefits of PARP inhibitors (olaparib, talazoparib), including a reduction in recurrence risk and improved survival in both early and metastatic disease. Somatic mutation analyses further expand therapeutic opportunities: ESR1 mutations support the use of modern endocrine therapies with SERDs (e.g., elacestrant), while alterations in the PI3K/AKT signaling pathway (PIK3CA, AKT1, PTEN) indicate eligibility for novel agents such as inavolisib or capivasertib... Molecular testing is crucial for the implementation of personalized treatment concepts in breast cancer. Early detection of germline and tumor mutations secures access to targeted therapies and improves pts prognosis."

Breast Cancer • Oncology • Solid Tumor • AKT1 • BRCA1 • BRCA2 • ER • PALB2 • PIK3CA • PTEN

Impact of anemia and its management on quality of life in metastatic castration-resistant prostate cancer patients treated with talazoparib plus enzalutamide (AUA 2026) - No abstract available

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

REAL-WORLD CHARACTERISTICS AND TREATMENT PATTERNS OF PATIENTS TREATED WITH TALAZOPARIB + ENZALUTAMIDE FOR METASTATIC CASTRATION-RESISTANT PROSTATE CANCER IN THE US COMMUNITY ONCOLOGY SETTING (ISPOR 2026) - "Descriptive analyses were stratified by prior androgen receptor pathway inhibitor(s) (ARPi) and/or docetaxel. Overall, 52 patients were included with median (IQR) age of 73 (65-80) years and median (IQR) 8 (5-12) months follow-up. This is the first real-world study of patient characteristics and use of T+E for mCRPC in the community oncology setting. Most patients had high metastasis burden, prior treatment with ARPi, and HRRm. This study will inform future real-world effectiveness analyses of T+E for mCRPC with HRRm."

Clinical • Metastases • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA2 • CDK12 • CHEK2 • HRD

Real-world patient characteristics and treatment patterns among patients with metastatic castration-resistant prostate cancer treated with talazoparib plus enzalutamide in the US. (ASCO-GU 2026) - "Of the 192 patients, 54.2% received androgen receptor pathway inhibitors (ARPi), 10.9% received apalutamide, 21.9% received enzalutamide, 29.7% received abiraterone, and 5.2% received darolutamide prior to mCRPC diagnosis. Additionally, 10.9% of patients received docetaxel prior to mCRPC diagnosis... This study highlights heterogeneous treatment and HRR testing patterns among patients with mCRPC receiving tala+enza. In this real-world dataset, over half of patients had received ARPi treatment prior to mCRPC. Despite limited follow-up, these findings offer early insights into real-world use and future evaluations should investigate real world clinical outcomes."

Clinical • Metastases • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • CDK12 • HRD • PALB2