Talzenna (talazoparib) / Pfizer, BioMarin - LARVOL DELTA

Testing the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial (clinicaltrials.gov) - P2 | N=88 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2027 ➔ Dec 2026

Enrollment closed • Trial completion date • Oncology • Ovarian Cancer • Solid Tumor • BARD1 • BRCA1 • BRCA2 • BRIP1 • FANCA • KRAS • RAD51 • RAD51C • RAD51D

Biomarker analysis in the China cohort of the Phase 3 TALAPRO-2 trial of first-line talazoparib (TALA) with enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2026) - No abstract available

Biomarker • Clinical • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Talazoparib (TALA) + enzalutamide (ENZA) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) with homologous recombination repair (HRR) gene alterations: safety analyses from the Phase 3 TALAPRO-3 study (ESMO 2026) - No abstract available

Clinical • Metastases • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

Prognostic utility of circulating tumor cell (CTC) count, CTC conversion, and CTC0 in TALAPRO-3: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA in homologous recombination repair (HRR) gene–mutated metastatic castration-sensitive prostate cancer (mCSPC) (ESMO 2026) - No abstract available

Circulating tumor cells • Clinical • Metastases • P3 data • Tumor cell • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

Patient-reported outcomes (PROs) in men with metastatic castration-sensitive prostate cancer (mCSPC) and homologous recombination repair (HRR) gene alterations receiving talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA: Results from the Phase 3 TALAPRO-3 study (ESMO 2026) - No abstract available

Clinical • Metastases • P3 data • Patient reported outcomes • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

Utility of ctDNA tumor fraction (TF) as a prognostic biomarker in TALAPRO-3: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA in patients (pts) with homologous recombination repair (HRR) gene–mutated metastatic castration-sensitive prostate cancer (mCSPC) (ESMO 2026) - No abstract available

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

Comparative Pharmacovigilance Analysis of Safety Signals Among Advanced Prostate Cancer Therapies Using FAERS (FDA Adverse Event Reporting System). (PubMed, Curr Oncol) - "A retrospective pharmacovigilance study of FAERS reports evaluated enzalutamide, darolutamide, apalutamide, abiraterone acetate, relugolix, niraparib/abiraterone, talazoparib, rucaparib, cabazitaxel, sipuleucel-T, and lutetium-177 vipivotide. The absence of a detected signal should not be interpreted as evidence of safety or equivalence, as reporting volume, detection bias, and statistical power varied across therapies. Overall, the therapies demonstrated distinct toxicity profiles, which may inform treatment selection, toxicity monitoring, and patient counseling."

Adverse events • Clinical • Journal • Retrospective data • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Disorders • Oncology • Prostate Cancer • Solid Tumor

TALAVE in Breast Cancer: BRCA1/2 Mutation-Dependent Immune Remodeling after PARP Inhibition with Limited Checkpoint Engagement. (PubMed, bioRxiv) - "In the TALAVE study, patients with advanced BRCA-mutant or wild-type (WT) HER2-negative BC received talazoparib followed by talazoparib plus avelumab. However, PD-L1+ cells were rapidly depleted or confined to immune-excluded regions, spatially segregating them from PD-1+ T cells, impairing effective checkpoint blockade. These findings suggest limited benefit of PD-1/PD-L1 blockade in augmenting PARPi activity and highlight the need for alternative strategies to sustain PARPi-induced immunity."

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

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

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

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

TALAPRO-2: 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-GU 2023) - P3 | " Pts randomized 1:1 to TALA 0.5 mg or PBO (all pts received ENZA 160 mg daily) were stratified by prior abiraterone or docetaxel for castration-sensitive PC and HRR gene alteration status. TALA + ENZA demonstrated statistically significant and clinically meaningful improvement in ibPFS over standard of care ENZA as 1L treatment in pts with mCRPC regardless of HRR status, while delaying time to worsening in GHS/QoL. There were no new safety signals; toxicity was generally manageable. Clinical trial information: NCT03395197."

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

Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): Safety analyses from the randomized, placebo (PBO)-controlled, phase 3 TALAPRO-2 study. (ASCO 2023) - P3 | "TALA 0.5 mg QD + ENZA 160 mg QD was generally manageable, with dose modifications of TALA and/or standard supportive care. Anemia was the most common TEAE and led to discontinuation of TALA in 8.3% of pts. G≥3 hematologic AEs typically occurred within 6 months of starting therapy and resolved in <1 month."

Clinical • Metastases • P3 data • Anemia • Back Pain • Fatigue • Genito-urinary Cancer • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Prostate Cancer • Solid Tumor • Thrombocytopenia • HRD

Advancing Homologous Recombination Repair Mutation Testing in Prostate Cancer in Australia: Shifting the Focus to Hormone Sensitive Prostate Cancer. (PubMed, Asia Pac J Clin Oncol) - "Recently, based on positive results from the phase III AMPLITUDE trial, niraparib was approved in the United States for the treatment of patients with BRCA2-mutated mHSPC. Positive results have also recently been obtained from the phase III TALAPRO-3 trial; talazoparib added to enzalutamide led to significantly better imaging-based progression-free survival than placebo plus enzalutamide among patients with mHSPC harboring HRR alterations...However, in Australia there is currently no reimbursement for HRR mutation testing in the mHSPC setting. Here, we review the current knowledge of the clinical relevance of HRR alterations and highlight the benefits of genomic profiling of hormone-sensitive disease prior to the development of castrate resistant disease."

Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA2 • HRD

Heterocyclic Scaffolds in PARP-1 Inhibition: An Emerging Strategy for Targeted Anticancer Therapy. (PubMed, Mini Rev Med Chem) - "Heterocyclic scaffolds offer a promising route toward next-generation PARP-1 inhibitors with enhanced efficacy, reduced resistance, and optimized safety, supporting personalized anticancer therapy."

Journal • Hematological Disorders • Oncology • BRCA • HRD • PARP2

TALAPRO-3: Talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations. (ASCO 2026) - P3 | "Key eligibility criteria are ECOG PS 0 or 1, presence of HRR gene alteration(s) (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) confirmed by tumor tissue and/or circulating tumor DNA testing, ongoing androgen deprivation therapy (ADT), no prior treatment with docetaxel (protocol amendment in Sept 2021), and ≤3 mo of ADT with or without an approved ARPI for mCSPC. Treatment with TALA+ENZA led to a statistically significant and clinically meaningful improvement in the primary endpoint of rPFS with a trend towards improved OS vs standard-of-care ENZA in pts with HRR-deficient mCSPC. The safety profile was generally manageable and consistent with those for TALA and ENZA."

Clinical • Late-breaking abstract • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Neutropenia • Oncology • Prostate Cancer • Renal Disease • Solid Tumor • ATM • BRCA • BRCA1 • BRCA2 • CDK12 • CHEK2 • FANCA • HRD • MLH1 • MRE11A • NBN • PALB2 • RAD51C

Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): Subgroup analyses of the all-comers cohort from TALAPRO-2 by homologous recombination repair (HRR) status (ESMO 2023) - P3 | "Methods Pts randomized 1:1 to TALA 0.5 mg or PBO, + ENZA 160 mg/day, were stratified by prior abiraterone or docetaxel for castration-sensitive PC (yes vs no) and by HRR status (HRR+ vs HRR-/unknown). Further data will be presented on baseline characteristics, efficacy, and TEAEs by treatment group for HRR+ and HRR-/unknown subgroups. Table: 1807P Conclusions TALA + ENZA demonstrated improvements in secondary efficacy endpoints over PBO + ENZA as 1st-line treatment in pts with mCRPC in both HRR+ and HRR-/unknown subgroups."

Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

The TALAPRO-3 study design: a plain language summary. (PubMed, Future Oncol) - P3 | "This study aims to find out if treatment with talazoparib plus enzalutamide increases the length of time the patients in the study live without their cancer getting worse, or them dying, compared with treatment with a placebo plus enzalutamide. The study will also measure how long the patients in the study live, the number and types of side effects they have, their general health and quality of life, and whether there are changes in how patients report their pain.Clinical Trial Registration: NCT03395197 (TALAPRO-2) (ClinicalTrials.gov)."

Journal • Genito-urinary Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor

Time to response with talazoparib (TALA) + enzalutamide (ENZA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) in TALAPRO-2 (ESMO 2025) - P3 | "Methods Pts were randomized 1:1 to ENZA 160 mg QD + TALA 0.5 mg QD (renal impairment, 0.35 mg) or PBO QD, stratified by homologous recombination repair (HRR) status (unselected only) and by prior abiraterone and/or docetaxel for castration-sensitive PC. Conclusions Time to tumor response was quick (median 1.9–3.5 mo) in pts with mCRPC receiving TALA + ENZA, regardless of HRR status, prior treatment, or visceral disease. Similar results were seen for PSAR."

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

Talazoparib in Patients With Solid Tumors With BRCA1/2 Mutation: Results From the Targeted Agent and Profiling Utilization Registry Study. (PubMed, JCO Precis Oncol) - "Talazoparib demonstrated antitumor activity in patients with advanced solid tumors and BRCA1/2 mutations, including cancer types for which poly ADP-ribose polymerase inhibitors are not yet US Food and Drug Administration-approved."

Journal • P2 data • Breast Cancer • Cardiovascular • Gastrointestinal Cancer • Heart Failure • Hepatocellular Cancer • Hepatology • HER2 Negative Breast Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HER-2

Impact of a cancer-associated mutation and post-translational modifications on poly(ADP-ribose) polymerase 2 inhibition | Poster Board #1118 (ACS-Fall 2026) - "Talazoparib is among the most potent PARP inhibitors and disrupts DNA repair and replication by blocking the catalytic active site and trapping PARP on damaged DNA...In the present project, we investigate how the D235G mutation, together with phosphorylation at S226, S232, and S353, influences PARP2 inhibition and the response of mutant PARP2 to pharmacological treatment. The results and implications for PARP2 function will be presented."

Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • Pancreatic Cancer • Solid Tumor • PARP2

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study. (PubMed, Eur J Cancer) - P3 | "Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations."

Journal • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Prostate Cancer • Renal Disease • Solid Tumor • Thrombocytopenia • HRD

Final results from ZZFIRST: A randomized phase 2 trial of enzalutamide (EZ) and talazoparib (TALA) in metastatic hormone-naïve prostate cancer (mHNPC). (ASCO 2026) - P2 | "EZ+TALA demonstrated promising antitumor activity in HV-mHNPC. The toxicity profile was consistent with prior AR+PARP trials, although two cases of AML were observed with prolonged TALA exposure. Paired tumor biopsies revealed mechanisms of tumor adaptation to ADT+EZ inhibition, supporting a biologically informed rationale for AR+PARP treatment intensification strategies in mHNPC."

Clinical • Metastases • P2 data • Acute Myelogenous Leukemia • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Oncology • Prostate Cancer • Solid Tumor • PARP1

Editorial Comment on Exploratory Time-Dependent Patterns in Estimated Treatment Effect of Talazoparib Plus Enzalutamide in HRR Non-Deficient or Unknown Metastatic Castration-Resistant Prostate Cancer: A Post Hoc Analysis of the TALAPRO-2 Trial. (PubMed, Int J Urol) - No abstract available

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