Zejula (niraparib)

P2, N=120, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Furthermore, we provide proof of concept that niraparib, an anticancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models. Our findings demonstrate that atherosclerosis is an SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease.

P2, N=64, Not yet recruiting, Qian Qin

P3, N=450, Not yet recruiting, Ivy Brain Tumor Center

Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCAm, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.

P1, N=236, Completed, Tesaro, Inc. | Active, not recruiting --> Completed

The validated method is currently employed to assess niraparib levels in human glioblastoma tissue, CSF, and plasma in an ongoing trial on newly diagnosed glioblastoma and recurrent IDH1/2(+) ATRX mutant glioma patients (NCT05076513). Initial results of calculated total (Kp) and unbound (Kp,uu) tumor-to-plasma partition coefficients indicate significant brain penetration ability of niraparib in glioblastoma patients.

P2, N=88, Recruiting, University of Maryland, Baltimore | Not yet recruiting --> Recruiting

Our study provides a comprehensive understanding of the biological role of CLDN18-based bioinformatics and machine learning analysis in STAD, shedding light on its prognostic significance and potential therapeutic implications. To fully elucidate the molecular intricacies of CLDN18, further investigation is warranted, particularly through in vitro and in vivo studies.

The primary end point is an investigator-assessed objective response rate in each cohort. Clinical Trial Registration: jRCT2011200023 (ClinicalTrials.gov).

P2, N=20, Not yet recruiting, Ibrahim Halil Sahin

Here, we review the newly approved PARPi plus ARSI treatments within the context of the mCRPC treatment landscape, provide an overview of practical considerations for the combinations in clinical practice, highlight the importance of HRR testing, and discuss the benefits of treatment intensification for patients with mCRPC.

P1/2, N=135, Recruiting, GlaxoSmithKline | Trial completion date: Nov 2025 --> Nov 2029 | Trial primary completion date: Jun 2025 --> Dec 2027

Inflammation-related blood data, such as neutrophil count, obtained at the initial pre-treatment visit might serve as potential predictors for prolonged olaparib treatment. While this study offers valuable insights into potential indicators for prolonged olaparib treatment, it underscores the need for more expansive research to strengthen our understanding of PARP inhibitors and optimize treatment strategies in ovarian cancer.

P3, N=733, Active, not recruiting, Tesaro, Inc. | Trial completion date: Mar 2024 --> Sep 2024

P2, N=51, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=112 --> 51 | Trial completion date: Mar 2027 --> Dec 2027 | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024

P2; N=45 --> 15 | Trial completion date: Nov 2024 --> Feb 2024 | Active, not recruiting --> Terminated; Funder terminated funding.

P1, N=0, Withdrawn, University College, London | N=15 --> 0 | Trial completion date: Jun 2025 --> Oct 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: Jul 2024 --> Oct 2023

P1/2, N=104, Active, not recruiting, University of Pennsylvania | Phase classification: P1b/2 --> P1/2

P1/2, N=30, Not yet recruiting, Rohan Garje

P1, N=204, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting

P3, N=8000, Not yet recruiting, University College, London

PARPi switch maintenance to consolidate a response to platinum-based therapy is recommended for earlier treatment lines to have the greatest impact on the chance of cure and length of survival. This article reviews the clinical utility of PARPis and how to integrate them into best practices.

P2, N=83, Active, not recruiting, Mario Negri Institute for Pharmacological Research | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Sep 2024

P1/2, N=38, Recruiting, Joseph Caster, Ph.D., M.D. | Phase classification: P1b/2 --> P1/2

No differences in survival outcomes were observed among patients with different BRCA statuses. Furthermore, for patients who had undergone two or more lines of chemotherapy before PARP inhibitor maintenance therapy, no negative effects of PARP inhibitors on subsequent treatment were found, regardless of BRCA status.

Even with short-term progression on PARP-I, local control combined with different platinum agents and PARP-I can be used to achieve good responses.

PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated.

P2, N=3000, Recruiting, Oslo University Hospital | N=1000 --> 3000

No differences were observed among the PARPi during first-line maintenance treatment. However, in the second-line maintenance treatment, significant differences were observed in the risk of experiencing CEIs, dose alteration possibilities, and discontinuation of PARPi between niraparib and olaparib (tablets). Moreover, our findings suggest that an age of 60 years may be a critical factor in selecting PARPi to reduce CEI incidence.

Based on the PROfound and TRITON3 trials, olaparib and rucaparib were respectively approved as monotherapy in pretreated patients with mCRPC and alterations in prespecified genes. The combinations of olaparib with abiraterone (PROpel) and niraparib with abiraterone (MAGNITUDE) were approved as first-line options in patients with mCRPC and alterations in BRCA1/2, whereas the combination of talazoparib with enzalutamide (TALAPRO-2) was approved in the same setting in patients with alterations in any of the HRR genes, which are found in around a quarter of patients with advanced prostate cancer...Future directions will include refining the treatment sequencing in patients with mCRPC in the clinic while taking into account the financial toxicity as well as the potential side effects encountered with these therapies and elucidating their mechanism of action in patients with non-altered HRR genes. Herein, we review the biological rationale behind using PARPis in mCRPC and the key aforementioned clinical trials that paved the way for these approvals.

P1, N=42, Recruiting, Nader Sanai | Trial completion date: Oct 2024 --> Feb 2025 | Trial primary completion date: Oct 2023 --> Aug 2024

P3; Not yet recruiting --> Recruiting

P2, N=12, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Recruiting --> Active, not recruiting | N=18 --> 12

Among the eligible 164 patients, 104 patients received olaparib and 60 patients received niraparib. Focusing on PARPi as first-line maintenance therapy for patients with EOC, this study represented the largest single-center real-world study in China to date. Two independent factors were identified to prolong the PFS of patients: BRCA mutated type and CR/PR after primary treatment, which should be further confirmed with long-term follow-up and large sample sizes.

P2, N=43, Active, not recruiting, Shadia Jalal, MD | Trial completion date: Nov 2024 --> Jul 2024 | Trial primary completion date: Nov 2023 --> Feb 2023

P2, N=180, Suspended, NRG Oncology | Trial primary completion date: Dec 2023 --> Jan 2028

P2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Sep 2023 --> Sep 2024

P1, N=31, Not yet recruiting, Sir Mortimer B. Davis - Jewish General Hospital | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

P2, N=390, Recruiting, ARCAGY/ GINECO GROUP | Trial completion date: Jan 2029 --> Feb 2030 | Trial primary completion date: Jan 2024 --> Feb 2027

P2, N=66, Recruiting, University of Oklahoma

P1, N=23, Terminated, Georgetown University | Trial completion date: Jul 2025 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2025 --> Oct 2023; Lack of accrual