Talzenna (talazoparib) / Pfizer, BioMarin - LARVOL DELTA

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

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

Phase I Trial of Concurrent Talazoparib and Consolidative Thoracic Radiotherapy for Patients with Extensive-Stage Small Cell Lung Cancer (ASTRO 2024) - "Materials/ Patients with ES-SCLC without disease progression following 4-6 cycles of platinum/etoposide +/- durvalumab were treated with talazoparib for 1 week prior to and then 2 weeks concurrently with CTRT (30Gy over 10 fractions) for a total of 3 weeks. Talazoparib can be administered safely with CTRT and was found to be tolerable. We identified the RP2D of concurrent RT and talazoparib as 1mg once daily for patients with ES-SCLC. Secondary efficacy endpoints and exploratory correlative assessments are ongoing."

Clinical • P1 data • Anemia • Anorexia • Dermatitis • Dermatology • Fatigue • Gastrointestinal Disorder • Immunology • Lung Cancer • Neutropenia • Oncology • Pain • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia

TalaCom: Phase Ib investigator-initiated trial combining talazoparib and axitinib in patients with DNA damage response mutated cancers or BRCA1/2 wildtype ovarian cancer incorporating prospective intrapatient dose titration (ESMO-TAT 2025) - P1 | "22/24 (92%) evaluable pts achieved RECIST SD or PR; 13/24 (54%) had tumor regressions, and 5/24 (21%) achieved RECIST PRs: 2 pts with BRCA2m HGSOC (one who progressed on prior olaparib, saruparib and camonsertib); 1 pt with BRCA2m peritoneal mesothelioma; 2 pts with mCRPC without DDR mutations (one who progressed on prior olaparib). The combination of axi + tala was generally manageable with durable antitumor activity in heavily pretreated HGSOC and CRPC pts, including pts who progressed on prior PARPi. Biomarker and PK analyses are ongoing."

Clinical • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • High Grade Serous Ovarian Cancer • Mesothelioma • Oncology • Ovarian Cancer • Peritoneal Mesothelioma • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • BRIP1 • CDK12 • CHEK2 • PALB2 • RAD51C

Emerging Therapeutic Synergies: Combining PD-1 Inhibitors With Poly-ADP-Ribose Polymerase (PARP) Inhibitors in the Treatment of Gynecologic Cancers. (PubMed, Cureus) - "In recurrent ovarian cancer, niraparib+pembrolizumab showed modest activity with durable responses in homologous recombination-deficient (HRD) tumors; olaparib+durvalumab demonstrated high activity in gBRCA platinum-sensitive relapse, and adding bevacizumab broadened benefit in non-BRCA cohorts. In the newly diagnosed disease, rucaparib+nivolumab maintenance failed to improve PFS versus rucaparib alone. Endometrial trials (olaparib+durvalumab; talazoparib+avelumab in mismatch repair-proficient disease) showed limited activity overall, with signals restricted to biomarker-selected subgroups...PARP+PD-1/PD-L1 combinations are most compelling in ovarian cancer, particularly in BRCA/HRD tumors and, in selected settings, with the addition of bevacizumab, while frontline maintenance benefit remains unproven and endometrial activity is modest. Biomarker-guided selection, rational triplets with non-cytotoxic partners, and optimized sequencing warrant further evaluation."

IO biomarker • Journal • Review • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Gynecology • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD • STING

ASCERTAIN: An open-label, randomized, phase 1, window-of-opportunity study to investigate the biological effects of AZD5305 and darolutamide alone or in combination in men with prostate cancer eligible for radical prostatectomy. (ASCO-GU 2024) - P1 | "The Phase 3 PROpel study showed that first-line combination treatment with olaparib and abiraterone significantly improved radiographic progression-free survival (rPFS) over abiraterone alone in pts with metastatic castration-resistant PC (mCRPC) (hazard ratio [HR], 0.66; 95% CI, 0.54 to 0.81; p<0.001). Similarly, the Phase 3 TALAPRO-2 study showed that first-line talazoparib with enzalutamide resulted in statistically significant improvement in rPFS over enzalutamide alone in pts with mCRPC (HR, 0.63; 95% CI, 0.51 to 0.78; p<0.0001)...Enrollment began in September 2023; sites across North America, Europe and Australia will enroll up to 120 patients. Clinical trial information: NCT05938270."

Clinical • P1 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • PARP2

In-silico discovery of novel PARP1 inhibitors for BRCA-mutated TNBC. (PubMed, In Silico Pharmacol) - "This study presents an integrated in-silico drug discovery workflow for the identification of new generation analogues of clinically approved drugs Olaparib and Talazoparib as potential PARP1 inhibitors. Overall, this study has underlined the usefulness of integrated in-silico approaches to accelerate the discovery of optimized PARP1 inhibitors for targeted cancer therapy. The online version contains supplementary material available at 10.1007/s40203-025-00543-x."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • HER-2

Novel therapeutic potential of the PARP inhibitor talazoparib in synovial sarcoma and its combined effect with ATR inhibitor. (PubMed, Discov Oncol) - "Talazoparib combined with ATR inhibitor possesses potential application as a therapeutic option for SS."

Journal • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • ANXA5 • CHEK1

Validated LC-MS/MS Method for Quantification and Pharmacokinetic Analysis of Talazoparib and Enzalutamide in Rats. (PubMed, Biomed Chromatogr) - "This study developed and validated an LC-MS/MS method for simultaneous quantification of Talazoparib and Enzalutamide in rat plasma using Apalutamide as the internal standard. In pharmacokinetic studies on male Wistar rats, Talazoparib showed a Cmax of 0.88 ng/mL at 3 h and an AUC0-t of 20 ng·h/mL, while Enzalutamide exhibited a Cmax of 76.18 ng/mL at 1 h and an AUC0-t of 1702 ng·h/mL; both had 24 h half-lives. The validated method enables sensitive, rapid, and reliable bioanalysis for preclinical pharmacokinetic evaluation."

Journal • PK/PD data • Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • 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

Estimated net benefit of talazoparib (TALA) + enzalutamide (ENZA) for patients (Pts) with mCRPC using a Q-TWiST analysis. (ASCO-GU 2026) - P3 | "Clinical Trial Registry Number: NCT03395197. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Prostate Cancer

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) - "Research Funding This study was funded by Pfizer Inc.. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

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

Efficacy of talazoparib and enzalutamide in mCRPC patients previously treated with androgen receptor pathway inhibitors (ARPI) or docetaxel: Post hoc analysis from both cohorts in TALAPRO-2 study (ESMO 2024) - P3 | "We conducted a post hoc analysis of radiographic progression free survival (rPFS) by prior androgen receptor pathway inhibitors (ARPI; abiraterone or orteronel) or by prior docetaxel. Time-to-event was summarized using the Kaplan-Meier method and compared between treatment arms using a stratified log-rank test except for the subgroup analysis of rPFS by prior ARPI/docetaxel which used an unstratified model due to small patient numbers in some of the subgroups. Although numbers in ARPI or docetaxel pretreated cohorts are small, this post hoc subgroup analysis shows the same improved trend in rPFS benefit by TALA+ENZA in both cohorts of the TALAPRO-2 study."

Clinical • Retrospective data • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

First-line talazoparib plus enzalutamide versus placebo plus enzalutamide in men with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: patient-reported outcomes from the randomised, double-blind, placebo-controlled, phase 3 TALAPRO-2 trial. (PubMed, Lancet Oncol) - P3 | "The demonstrated delays in definitive deterioration in GHS/QoL, urinary symptoms, and other functioning and symptom scales with talazoparib plus enzalutamide compared with placebo plus enzalutamide in patients with HRR-deficient metastatic castration-resistant prostate cancer provide insight that might inform clinical decisions for these patients."

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

A Study of ART4215 for the Treatment of Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=93 | Completed | Sponsor: Artios Pharma Ltd | N=390 ➔ 93 | Active, not recruiting ➔ Completed

Enrollment change • Monotherapy • Trial completion • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • HER-2

MEOX2 Enhances DNA Repair and Therapy Resistance in Glioblastoma Stem Cells via PARP1 Interaction. (PubMed, Cancer Lett) - "Using a GLICO (GLioblastoma Cerebral Organoid) model, we show that MEOX2 knockdown impairs tumor growth and increases sensitivity to temozolomide (TMZ)...Consistent with this, MEOX2-depleted cells exhibit reduced PARylation levels and increased sensitivity to the PARP1 inhibitor Talazoparib, highlighting a potential therapeutic vulnerability. Altogether, our findings reveal a previously unrecognized role for MEOX2 in the DNA damage response of GSCs, particularly in promoting survival and recovery after chemotherapy and ionizing radiation. These results also suggest that MEOX2 functions as a partner of PARP1 and may represent a promising therapeutic target in GBM."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MEOX2 • PARP1

Avelumab Plus Talazoparib in Patients With BRCA1/2- or ATM-Altered Advanced Solid Tumors: Results From JAVELIN BRCA/ATM, an Open-Label, Multicenter, Phase 2b, Tumor-Agnostic Trial. (PubMed, JAMA Oncol) - P2 | "Antitumor activity for the combination of avelumab and talazoparib in patients with BRCA1/2 alterations was observed in some patients with BRCA1/2-associated tumor types and uterine leiomyosarcoma; benefit was minimal in non-BRCA-associated cancer types. ClinicalTrials.gov Identifier: NCT03565991."

Journal • P2b data • Pan tumor • Gastrointestinal Cancer • Hepatology • Leiomyosarcoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • Uterine Cancer • Uterine Leiomyosarcoma • ATM • BRCA • BRCA1 • BRCA2 • PARP1 • PD-L1 • TMB

A Phase 2 Trial of Talazoparib and Avelumab in Genomically Defined Metastatic Kidney Cancer. (PubMed, Eur Urol Oncol) - "The first clinical study of combination PARPi and ICB therapy in advanced kidney cancer did not show clinical benefit in multiple genomically defined metastatic RCC cohorts or RMC."

Journal • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Fatigue • Genito-urinary Cancer • Hematological Disorders • Kidney Cancer • Kidney Medullary Carcinoma • Oncology • Pain • Renal Cell Carcinoma • Solid Tumor • Von Hippel-Lindau Syndrome • FH

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

Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer. S1929. (PubMed, J Thorac Oncol) - "Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations."

IO biomarker • Journal • P2 data • Lung Cancer • Small Cell Lung Cancer • Solid Tumor • SLFN11

SWOG S1929: Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer (ES-SCLC). (ASCO 2023) - P2 | "In a retrospective analysis of a study with veliparib (PARP inhibitor [PARPi]) and temozolomide in patients with SCLC, Schlafen-11 (SLFN11) predicted PFS and OS benefit for the addition of PARPi. This study met its primary endpoint demonstrating that maintenance AT improved PFS in SLFN11-selected patients with ES-SCLC. Hematologic toxicity was increased with AT as expected, with majority being grade 3 anemia. This study demonstrates the feasibility of conducting biomarker selected trials in SCLC, paving the way for future evaluation of novel therapies in selected SCLC populations."

Clinical • IO biomarker • P2 data • Anemia • Febrile Neutropenia • Immune Modulation • Lung Cancer • Neuroendocrine Tumor • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • SLFN11

SWOG S1929: Testing Maintenance Therapy for Small Cell Lung Cancer in Patients With SLFN11 Positive Biomarker (clinicaltrials.gov) - P2 | N=103 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Nov 2025 ➔ Jan 2027

Biomarker • Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SLFN11

Antibody Drug Conjugate Sacituzumab Govitecan Enables A Sequential TOP1/PARP Inhibitor Cancer Therapy Strategy in Breast Cancer Patients. (PubMed, Clin Cancer Res) - P1/2 | "While SG dosed concurrently with talazoparib is not tolerated clinically due to an insufficient therapeutic window, sequential dosing of SG then talazoparib proved a viable strategy. These findings support further clinical development of the combination and suggest that ADC-based therapy may facilitate novel, mechanism-based dosing strategies."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TOP1

Use of circulating tumor DNA (ctDNA) to complement tumor tissue homologous recombination repair (HRR) gene alteration testing in TALAPRO-2, a phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2023) - P3 | "Results show 95% agreement between prospective tissue and ctDNA-based HRR status using FoundationOne, consistent with tumor vs ctDNA results recently reported (Tukachinsky. Clin Cancer Res. 2021;27:3094–3105)."

Circulating tumor DNA • Clinical • Metastases • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 Mutation-Positive, Early-Stage Triple-Negative Breast Cancer: Results of a Phase II Study. (PubMed, Oncologist) - P2 | "Neoadjuvant talazoparib monotherapy was active despite pCR rates not meeting the prespecified threshold; these rates were comparable to those observed with combination anthracycline- and taxane-based chemotherapy regimens. Talazoparib was generally well tolerated."

Journal • P2 data • Breast Cancer • Hematological Disorders • Neutropenia • Oncology • Renal Disease • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2