Talzenna (talazoparib)

Our preclinical and clinical data strongly support the further development of PARPis together with DNA damage stress-inducing treatment regimens for DHG-H3G34R_ATRX.

In real-world practice, PARPis are well-tolerated with promising TTF in gBRCA1/2 and gPALB2 carriers. Further studies will delineate the clinical efficacy of PARPis in other MBC subsets, such as sBRCA mutations, HER2-positive disease, and CNS metastasis.

Introduction: TALAPRO-2 (NCT03395197) demonstrated that first-line talazoparib + enzalutamide significantly improved radiographic progression-free survival versus placebo + enzalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC). These results are supportive of the ability of F1LCDx to sensitively detect alterations in HRR genes, and the likely overall modest impact of CHiP in calling HRR gene alteration status in this study. These results support the complementary benefits of ctDNA testing to tumor tissue testing in assessing current disease alteration status, particularly AR.

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.

P1, N=26, Active, not recruiting, University of Michigan Rogel Cancer Center | Recruiting --> Active, not recruiting

P2, N=28, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.

P1, N=24, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Apr 2025 --> Jun 2024 | Trial primary completion date: Apr 2025 --> May 2024

These include inhibitors of signaling pathways such as TGF-β, Wnt/β-catenin, Notch, TNF-α/NF-κB and EGFR, as well as immune checkpoint inhibitors, such as pembrolizumab, 2laparib, and talazoparib have been widely explored. This article reviews recent developments in EMT in TNBC invasion and metastasis and potential targeted therapy strategies.

Approximately 15% of TNBC patients have a germline mutation in BRCA1 and/or BRCA2, and for these patients, innovative therapeutic options such as olaparib and talazoparib, which are PARP inhibitors, are available. Sacituzumab govitecan (SG) is a humanized monoclonal antibody-drug conjugate directed against the surface antigen of human trophoblastic cells (Trop-2) expressed in approximately 90% of TNBC, coupled with SN-38, the active metabolite of irinotecan, a topoisomerase I inhibitor. Here, we present the case of a woman who was initially diagnosed with localized luminal B breast cancer (ER-positive; HER2-negative) and was treated with curative therapy. However, she later experienced a recurrence with metastatic TNBC (ER-negative/HER2-negative) and received treatment with sacituzumab govitecan, which resulted in prolonged disease control.

Olaparib and talazoparib are PARP inhibitors (PARPi) are being employed for the monotherapies in case of the deleterious germline HER2-negative and BRCA-mutated breast cancer. The PARPi have been found its place in the all different types of Breast Cancers and have shown potential benefits. The purpose of this review is to provide an update on the oral poly(ADP-ribose) polymerase (PARP)inhibitors for the improvement in the treatment and management of Breast Cancer.

No abstract available

Introduction: TP-2 (NCT03395197) demonstrated statistically significant improvement in rPFS with 1L talazoparib (TALA) + enzalutamide (ENZA) in patients (pts) with mCRPC with and without HRR gene alterations (HRRm; prospectively determined). Broad differential efficacy benefit was evident for TALA+ENZA vs PBO+ENZA across multiple molecular subgroups and was most pronounced for the BRCA1 - PALB2 - BRCA2 axis and CDK12.

Methods Transcriptomic analysis of baseline or on-treatment (PARPi, talazoparib) biopsies from patients with BRCA-associated TNBC from the TALAVE clinical trial (NCT03964532) were assessed using the NanoString-IO360™ and Digital Spatial Profiling (DSP) platforms. Tumor-bearing mice (K14-Cre/Brca1f/f/p53f/f ) were treated with vehicle or PARPi (olaparib) for 5 days and gene expression profiling, flow cytometry and mass spectrometry-based metabolome analysis were utilized to determine the metabolic profile of tumors. To inhibit lipid synthesis, mice were treated with fatostatin (SREBP1 inhibitor) or denifanstat (FASN inhibitor)...Ethics Approval The present study was approved by BWH CMM IACUC, protocol number is 2020N000142 and by Dana-Farber Cancer Institute, protocol number is 20–627. Study drugs were provided by Pfizer, as part of an alliance between Pfizer and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

PARP inhibitors, such as Olaparib, Rucaparib, Niraparib, and Talazoparib have been approved in a number of cancers including BRCA 1/BRCA2 associated malignancies although there are many difficulties as therapeutical resistance. It emphasizes that isoxazole-based PARP inhibitors compounds could be novel anti-cancer drugs. Through this review, we hope to grow a curiosity in additional explorations of isoxazole-based PARP inhibitors and their applications in the trends of novel insights towards precision cancer therapy.

We developed two 89Zr-radiolabeled nanocarriers based on 4-armed-starPEG40kDa with or without talazoparib (TLZ), a potent PARPi, as surrogates for the PEG-TLZ4 therapeutic scaffold. For PET imaging, PEG-DFB4 and PEG-DFB1-TLZ3 were radiolabeled with 89Zr by replacing one or all four TLZ on PEG-TLZ4 with deferoxamine B (DFB)...Although heterogeneous, prostate cancer xenografts had low EPR. These starPEG nanocarriers could be used as PET imaging surrogates to predict drug delivery and efficacy.

This study provides pre-clinical evidence that AKT inhibitors combined with PI3K inhibitors, cisplatin, or vincristine exhibit additive/synergistic anti-MB activity, and lower doses could be used. The latter also applied to one MB line grown as spheroids, further supporting their future potential use.

This review and hypothetical case study illustrate the role of oncology nurses and APPs in the administration of talazoparib plus enzalutamide and the management of adverse events to ensure safe and effective use in clinical practice. Oncology nurses and APPs play an important role in the dosing and administration of talazoparib plus enzalutamide and can recognize and manage adverse events in patients with HRR-deficient mCRPC.

P2, N=197, Active, not recruiting, Bryan Schneider, MD | Recruiting --> Active, not recruiting

Currently, four PARPi including Olaparib, Rucaparib, Niraparib, and Talazoparib have been developed and greatly improved clinical outcomes in cancer patients. However, accumulating evidences suggest that required or de novo resistance emerged. In this review, we discuss the molecular mechanisms leading to PARPi resistances and review the potential strategies to overcome PARPi resistance.

Interestingly, antitumor activity was also observed irrespective of DDR gene mutations, highlighting BRCAness phenotype with androgen receptor blockade resulting in synergistic activity between ARSIs and PARPi. In this review, we discuss the clinical efficacy and safety data of the combination of PARPi plus ARSI in all Phase 3 randomized controlled trials (RCTs), emphasizing strategies for patient selection and highlighting emerging trends based on clinical trial data.

This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.

P2, N=3791, Recruiting, American Society of Clinical Oncology | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Jun 2026

P2, N=30, Recruiting, Stanford University | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

The molecular dynamic approach and MM-PBSA investigation along with PCA study revealed that the complex of Naringin, with 4ZZZ (PARP1) and, 2ABL (ABL1), are highly stable compared to that of imatinib and talazoparib. Cytotoxicity assay was performed on two different glioblastoma cell lines C6 and U87MG cells. Naringin demonstrates a higher cytotoxic potency against U87MG human glioblastoma cells compared to C6 rat glioma cells.

We explored the synergistic cytotoxicity of histone deacetylase inhibitors (HDACis), poly(ADP-ribose) polymerase inhibitors (PARPis), and decitabine in breast (MDA-MB-231 and MCF-7) and ovarian (HEY-T30 and SKOV-3) cancer cell lines that were exposed to HDACi (panobinostat or vorinostat), PARPi (talazoparib or olaparib), decitabine, or their combinations. These results indicate that HDACi, PARPi, and decitabine combinations should be further explored in these tumor types. Further clinical validation is warranted to assess their safety and efficacy.

P2, N=78, Recruiting, Fundacion Oncosur

P2; Active, not recruiting --> Completed

We conclude that [18F]FTT can image target engagement by PARPi, but larger studies are needed to determine whether [18F]FTT uptake can predict response to PARPi and whether uptake of [18F]FTT in bone marrow may be an early predictor of hematologic toxicity.

P1; Active, not recruiting --> Completed

P1/2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P1, N=24, Recruiting, Peter MacCallum Cancer Centre, Australia | Trial completion date: Dec 2025 --> Jun 2029 | Trial primary completion date: Dec 2025 --> Jun 2029

We propose that talazoparib promotes low-dose, CtIP/MRE11-dependent resection and increases the reliance of irradiated HR-proficient cancer cells, on Polθ-mediated alt-EJ. Combination of Polθ inhibitors with talazoparib suppresses this option and causes further radiosensitization. The results suggest that Polθ inhibition may be exploited to maximize talazoparib radiosensitization of HR-proficient tumors in the clinic.

P2, N=50, Recruiting, Centre Francois Baclesse | Trial completion date: Dec 2023 --> Dec 2025

P1, N=25, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024

PTEN mutations/loss patients derived limited clinical benefit. Further study is needed to determine whether PTEN is prognostic or predictive of response to PARP inhibitors.

Finally, drug sensitivity analysis revealed that ALDOB increased the sensitivity of gastric cancer cells to most antitumor drugs, especially talazoparib, XAV939, and FTI-277. And ALDOB significantly inhibited proliferation and migration, delayed glycolysis in GC cells. Consequently, our study suggests that ALDOB may be a potential target for the clinical treatment of gastric cancer.

Additionally, the CDK4/6 inhibitor palbociclib enhanced the sensitivity of breast cancer cells to talazoparib through FANCI inhibition. These findings highlight the potential of targeting FANCI to enhance the efficacy of PARP inhibitors in treating breast cancer.

P2, N=106, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Mar 2027 --> Nov 2026 | Trial primary completion date: Mar 2025 --> Nov 2023

The current randomized controlled trial evidence network does not permit robust comparisons between niraparib plus AAP and other PARPi regimens for patients with 1L BRCA-positive mCRPC. Decision-makers should scrutinize any ITC results in light of their limitations. Real-world evidence combined with clinical experience should inform treatment recommendations in this indication.

PARP inhibitors such as olaparib and talazoparib have demonstrated efficacy in patients with BRCA mutations, leading to FDA approvals for ovarian and breast cancers. Similarly, in the second case, rucaparib demonstrated effectiveness as a maintenance therapy subsequent to achieving a near-complete response to taxane and platinum-based treatment. These findings emphasize the promising role of rucaparib in managing metastatic breast cancer in patients with BRCA1/2 mutations, further contributing to the expanding armamentarium of targeted therapies in breast cancer care.

Moreover, our analysis revealed alterations in signaling pathways associated with the observed antitumor efficacy. This study presents a novel and efficacious therapeutic approach for MRT, along with a promising candidate biomarker for predicting tumor response.