Talzenna (talazoparib)

P1/2, N=40, Active, not recruiting, Hospices Civils De Lyon | Recruiting --> Active, not recruiting

MAICs showed improved clinical benefit with TALA+ENZA versus OLAP+AAP and NIRA+AAP across multiple mCRPC populations and endpoints. Despite limitations of indirect comparisons, findings support TALA+ENZA as a first-line treatment option for mCRPC.

ASTX727 plus talazoparib produces significant myelosuppression without other adverse events. Modest methylation changes in PBMCs were detected. There were no objective responses, but some heavily pretreated patients had stable disease for >4 months despite the attenuated doses.

Her recent PNAS Inaugural Article identifies two escape routes in BRCA1-mutant tumors treated with talazoparib, pointing to new combination therapies. She emphasizes the value of mentorship and persistence in science.

Among patients with a reported germline mutation, 36.1% had a BRCA1, 62.9% a BRCA2 and 1.0% a PALB2 mutation. In summary, outcomes were comparable to those reported in pivotal trials despite later-line use of PARP-inhibitors in this analysis.

In another, an HR repair proficient tumor subclone lacking Shieldin 2 expression expanded during treatment and accounted for intrinsic resistance. Our findings highlight the need to determine intrinsic and anticipate acquired resistance pathways in treatment-naïve tumors and support combining PARPi with targeted agents to improve outcomes in the neoadjuvant setting.

P1/2, N=24, Active, not recruiting, Georgetown University | Trial completion date: Mar 2026 --> Apr 2027 | Trial primary completion date: Mar 2026 --> Apr 2027

The PARP inhibitor talazoparib (TAL) combined with the alkylating agent temozolomide (TMZ) produces synergistic cytotoxicity selectively in mtp53, but not wild-type p53 (wtp53), breast cancer cells and organoids. These findings reveal a previously unrecognized mechanism by which the mutant p53-PARP axis enables replication stress tolerance and drives cancer metastasis. We show mutation of p53 in TNBC provides an additional biomarker-guided framework to improve PARPi therapeutic outcomes.

P2, N=88, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2026 --> Dec 2027

SANE-TZL markedly improves the delivery efficiency and antitumor activity of TZL in breast cancer models while maintaining a favorable safety profile. By combining a functional stearic acid carrier with TZL, this nanoemulsion formulation represents a safe and potent strategy to enhance PARP inhibitor-based chemotherapy in breast cancer, and it may provide a basis for further mechanistic studies on DNA damage response modulation.

P1/2, N=75, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2025 --> Jun 2026

The SN-38 and talazoparib were identified as possible RNF20-targeting agents through drug susceptibility analysis. It was revealed that missense mutations are most frequent type of variations, which is revealed by functional enrichment analysis, mutation profiling, RNA modification mapping and analysis of genomic heterogeneity of the RNF20 related genes within the framework of glioblastoma, glioma, low-grade glioma in addition to thyroid cancer. Collectively, these results support the exculpatory role of RNF20 in the treatment of different types of cancer, which could help to certify the usage of this biological molecule as a predictive biomarker of treatment response.