RegulationConditional marketing approval (CN), Special Review Project (CN), Fast Track (US), Breakthrough Therapy (US), Orphan Drug (US), Priority Review (CN)

Structure/Sequence

Molecular FormulaC19H20N4O

InChIKeyPCHKPVIQAHNQLW-CQSZACIVSA-N

CAS Registry1038915-60-4

View All Structures (2)

232

Clinical Trials associated with Niraparib Tosylate

NCT06412120

/ Not yet recruitingPhase 4IIT

Single-Arm, Prospective, Multicenter Study Evaluating Safety, Tolerability, and Metabolism of Niraparib as Maintenance Following Front-Line Treatment for Ovarian Cancer in Women of African Ancestry

The purpose of this study is to identify the genetic characteristic(s), specifically degree of African ancestry, and environmental characteristic(s) that appear to be related to the effects, both good and bad, that the maintenance treatment has women with ovarian cancer. In this study, an investigational medication called niraparib is being tested for the treatment of ovarian cancer. Niraparib works by blocking the ability of cancer cells to fix their genes. Cancer cells with damaged genes have a harder time growing and spreading in the body and can even die.

Start Date01 Apr 2025

Sponsor / Collaborator

University of Miami

[+1]

NCT05672095

/ Not yet recruitingPhase 1/2IIT

Phase I/II Trial of Niraparib/Selenium Combination Treatment in Patients With BRCA1/2-Wild Type Recurrent Platinum-Resistant Ovarian Cancer

This phase I/II trial tests the safety, side effects and best dose of a combination therapy (niraparib and selenium) in treating patients with BRCA negative ovarian cancer that has come back (recurrent) and does not respond to platinum based therapy (platinum resistant). Selenium is a form of the trace element with potential antineoplastic activity which may help block the formation of growths that may become cancer. Niraparib is in a class of medications called poly (ADP-ribose) polymerase inhibitors. It works by killing cancer cells and helps maintain the response of certain types of ovarian, fallopian tube and peritoneal cancers. Giving selenium and niraparib may kill more cells in patients with ovarian cancer.

Start Date18 Jan 2025

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

NCT06747845

/ Not yet recruitingPhase 2IIT

ParpVax2: a Phase II Study of Maintenance Niraparib Plus Ipilimumab in Patients with Metastatic Pancreatic Cancer Whose Disease Has Not Progressed on Platinum-Based Therapy

The main goal of this study is to look at the effectiveness and anti-tumor activity (preventing growth of the tumor) of the drugs niraparib and ipilimumab, on the patients and their pancreatic cancer. This study will involve two different treatment arms. In Arm A, patients will receive niraparib plus ipilimumab. In Arm B, patients will receive standard chemotherapy.
The main questions the study aims to answer are:
* Does niraparib plus ipilimumab slow down tumor growth in patients with pancreatic cancer?
* What medical problems do participants have when taking niraparib plus ipilimumab?
Participants will:
* Undergo screening procedures to evaluate their cancer, overall health, and suitability for the study
* After passing screening, will be randomized to Arm A or B and be scheduled to receive niraparib plus ipilimumab (Arm A) or chemotherapy (Arm B)
* Receive niraparib plus ipilimumab every 3 weeks (Arm A)
* Receive chemotherapy every 2 weeks (Arm B)
* Visit the clinic for regular checkups and tests

Start Date06 Jan 2025

Sponsor / Collaborator

Abramson Cancer Center

[+3]

100 Clinical Results associated with Niraparib Tosylate

100 Translational Medicine associated with Niraparib Tosylate

100 Patents (Medical) associated with Niraparib Tosylate

674

Literatures (Medical) associated with Niraparib Tosylate

01 Feb 2025·Free Radical Biology and Medicine

PARP1 inhibitor niraparib exerts synergistic antimyeloma effect with bortezomib through inducing DNA damage and inhibiting DNA repair

Article

Author: Zhang, Haiyan ; Zhao, Qizhi ; Wu, Jinpeng ; Li, Lining ; Liu, Hongbo ; Cheng, Mengdi ; Chen, Xiequn

Despite the improvements in outcomes for patients with multiple myeloma (MM) over the past decade, the disease remains incurable, and even those patients who initially respond favorably to induction therapy eventually suffer from relapse. Consequently, there is an urgent need for the development of novel therapeutic agents and strategies to enhance the treatment outcomes for patients with MM. The proteasome inhibitor bortezomib (BTZ) elicits endoplasmic reticulum (ER) stress and oxidative stress in MM cells, subsequent DNA damage, ultimately inducing cell apoptosis. Poly (ADP-ribose) polymerase 1 (PARP1) acts as a pivotal enzyme for DNA repair and thus deficient PARP1 renders cells more susceptible to DNA-damaging agents. Conceivably, targeting PARP1 may enhance BTZ-induced DNA damage and cell death in MM cells. In this study, Colony formation, CCK-8, and EdU-labeling assays were conducted to evaluate the effects on MM cell proliferation. The ZIP score was used to assess synergy. Apoptosis and intercellular ROS levels were analyzed using flow cytometry and fluorescence microscopy, respectively. Immunofluorescence and Western blot analyses were used to assess protein expression. The correlation between PARP1 expression levels and the clinical prognosis was examined by tumor-related databases and bioinformatics. The results show that PARP1 is overexpressed in patient MM cells and is associated with a poor prognosis. PARP1 inhibitor niraparib decreases MM cell growth and arrests cell cycle progression at the G2/M phase. When combined with BTZ, it synergistically increases DNA damage, inhibits proliferation, and induces apoptosis. Mechanistically, Niraparib facilitates BTZ-induced ROS elevation, causing DNA double-strand breaks (DSBs), and simultaneously inhibits lesion repair by impeding the expression of repair proteins XRCC1 (X-ray repair cross-complementing protein 1)and POLβ (DNA polymerase beta). Overall, Niraparib plus bortezomib represent a promising approach for treatment of MM.

01 Feb 2025·International Journal of Radiation Oncology*Biology*Physics

Stereotactic Body Radiation Therapy for Oligoprogressive Ovarian Cancer Patients Treated During Poly(ADP-Ribose)-Polymerase Inhibitor Maintenance: Efficacy and Adverse Events From the Epimetheo Retrospective Study

Article

Author: Fagotti, Anna ; Rosa, Autorino ; Valeria, Epifani ; Perrucci, Elisabetta ; Vanda, Salutari ; Simona, Lucci ; Ferrandina, Gabriella ; Epifani, Valeria ; Gabriella, Ferrandina ; Aida, Di Stefano ; Andrea, Russo Silvio ; Deodato, Francesco ; Distefano, Maria Grazia ; Grazia, Distefano Maria ; Elisabetta, Perrucci ; Giannini, Roberta ; Autorino, Rosa ; Cilla, Savino ; Graziana, Ronzino ; Gabriella, Macchia ; Antonietta, Gambacorta Maria ; Maura, Campitelli ; Macchia, Gabriella ; Giovanni, Scambia ; Di Stefano, Aida ; Gambacorta, Maria Antonietta ; Anna, Fagotti ; Vittoria, Balcet ; Roberta, Giannini ; Russo, Silvio Andrea ; Viola, De Luca ; Donato, Pezzulla ; Rinaldi, Raffaella ; Palluzzi, Eleonora ; Francesco, Deodato ; Savino, Cilla ; Campitelli, Maura ; Marchetti, Claudia ; Claudia, Marchetti ; Salutari, Vanda ; Balcet, Vittoria ; Eleonora, Palluzzi ; De Luca, Viola ; Lucci, Simona ; Scambia, Giovanni ; Raffaella, Rinaldi ; Ronzino, Graziana ; Russo, Donatella ; Pezzulla, Donato ; Donatella, Russo

PURPOSEThe aim of this observational, retrospective, multicenter study (Epimetheo) was to analyze the activity and the safety of stereotactic body radiation therapy (SBRT) during poly(ADP-ribose)-polymerase inhibitor (PARPi) maintenance in a series of oligometastatic ovarian cancer (OC) patients.METHODS AND MATERIALSPatients treated with PARPi in maintenance setting received SBRT if oligometastatic progression occurred. Maintenance treatment was continued until the extensive progression of the disease. The primary endpoints of the study were as follows: next systemic treatment change-free survival (NEST-FS) and acute and late toxicity; the secondary endpoints were as follows: the rate of clinical complete response (CR), the 2-year actuarial local control (LC, progression of disease inside SBRT field) rate on "per lesion" basis, the 2-year actuarial progression-free survival, and 2-year overall survival (OS).RESULTSFrom April 2018 to September 2023, SBRT was used to treat 74 OC patients with a total of 158 lesions (98 lymph nodes and 60 parenchymal lesions) under PARPi maintenance. Olaparib, niraparib, and rucaparib were administered to 41.9%, 48.6%, and 9.5% of patients, respectively. CR, partial response, stable disease, and progressive disease were observed in 115 (72.8%), 32 (20.3%), 9 (5.7%), and 2 lesions (1.3%), respectively. Severe toxicities were reported in less than 3% of patients. The actuarial median NEST-FS was 10 months, with a range of 6.7-13.3 months. The 12- and 24-month actuarial NEST-FS rates were 44.9% and 31.4%, respectively. The 2-year actuarial LC, progression-free survival, and OS were 68.1%, 22.5%, and 77%, respectively with differences in figures between complete and incomplete responders. The achievement of CR was found to be correlated with an improvement in LC and OS.CONCLUSIONSThis study reports the activity and the low toxicity profile of SBRT in association with PARPi in oligometastatic OC patients. A rapid, minimally invasive, and cost-effective treatment such as SBRT may be proposed as a means of prolonging NEST-FS and maintaining an effective treatment regimen involving PARPi.

01 Feb 2025·European Journal of Obstetrics & Gynecology and Reproductive Biology

Haematological toxicity of PARP inhibitors in advanced ovarian cancer: A systematic review and meta-analysis

Article

Author: Cormio, Gennaro ; Maiorano, Brigida Anna ; Loizzi, Vera ; Pio Maiorano, Mauro Francesco

BACKGROUNDPoly (ADP-ribose) polymerase inhibitors (PARPis) are effective treatment options for patients with advanced ovarian cancer (OC). A typical adverse event (AE) of these agents is haematological toxicity, which represents the leading cause of treatment modification and discontinuation. This systematic review and meta-analysis aimed to analyse the risk of haematological AEs, including anaemia, neutropenia and thrombocytopenia due to the use of PARPis in patients with OC.METHODSThis systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. PubMed, EMBASE and Cochrane databases, and international meeting abstracts were searched systematically for clinical trials concerning the use of PARPis in patients with OC. The search deadline was 30 March 2024. The pooled incidence of all grades and grade 3or more (≥G3) anaemia, neutropenia and thrombocytopenia were analysed. Subsequently, risk ratios (RRs) were calculated for all grades and ≥G3 AEs of PARPis compared with non-PARPis from randomized controlled trials.RESULTSIn total, 12 phase II/III trials with olaparib, niraparib and rucaparib were included in this study. Anaemia was the most common all grade (28.8 %) and ≥G3 (12.1 %) AE. The administration of PARPis increased the risk of developing all grade anaemia [risk ratio (RR) = 2.44], neutropenia (RR = 3.15) and thrombocytopenia (RR = 4.66) significantly compared with non-PARPis. Similarly, a significant increase in the risk of ≥G3 anaemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a non-significant increase in the risk of neutropenia (RR = 3.41) were detected.CONCLUSIONSIn patients with advanced OC, PARPis increase the risk of haematological toxicity compared with other treatments (high-quality evidence). Clinicians should be aware of this risk and the correct management, as these drugs are highly employed in these patients.

207

News (Medical) associated with Niraparib Tosylate

15 Jan 2025

·ir.zailaboratory.com

Zai Lab Announces Positive Topline Results for TIVDAK in the China Subpopulation of the Global Phase 3 innovaTV 301 Trial in Patients with Recurrent or Metastatic Cervical Cancer

Improved overall survival (OS), progression-free survival (PFS) and confirmed objective response rate (ORR) were observed in the China subpopulation treated with TIVDAK compared to chemotherapy, consistent with those in the global population The safety profile of TIVDAK among the China subpopulation was manageable and consistent with that observed in the global population Zai Lab intends to submit a New Drug Application (NDA) to China’s National Medical Products Administration (NMPA) in the first quarter of 2025 Zai Lab will leverage its commercial footprint of ZEJULA in women’s cancer to bring the medicine to patients in China if approved SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 15, 2025-- Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today announced positive topline results from the China subpopulation of the global Phase 3 innovaTV 301 study, demonstrating a clinically meaningful improvement in overall survival with TIVDAK treatment for patients with previously treated recurrent or metastatic cervical cancer compared to chemotherapy. The China subpopulation results were consistent with those in the global population: TIVDAK demonstrated a 45% reduction in the risk of death compared to chemotherapy (HR: 0.55 [95% CI: 0.27-1.15] in the China subpopulation who had received prior standard systemic therapies, with more than half of this Chinese population having received prior anti-PD(L)1 therapy. Median OS for patients treated with TIVDAK was not reached versus chemotherapy 10.7 months [95% CI: 6.0-not reached] with a median follow-up of 11.5 months. Secondary endpoints of PFS and confirmed ORR also favored treatment with TIVDAK compared to chemotherapy. The safety profile of TIVDAK in the China subpopulation was manageable and consistent with the global profile. “Recurrent or metastatic cervical cancer remains a significant challenge for patients, highlighting a critical unmet need for effective treatments that extend survival after relapse,” said Dr. Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab. “The consistent and positive results in the China subpopulation of the global Phase 3 study reinforce the potential for TIVDAK, the only ADC therapy in this disease setting, to increase options in this therapeutically unmet clinical setting. If approved, we expect TIVDAK to add to ZEJULA and augment our commercial franchise in women’s tumors.” “There are approximately 150,000 new cases of cervical cancer annually in China1, and patients face limited treatment options once their cancer recurs or spreads after initial treatment,” said Dr. Lingying Wu, Professor of the Department of Gynecologic Oncology of National Cancer Center / Cancer Hospital Chinese Academy of Medical Sciences. “While the recent adoption of immunotherapy as a first-line treatment in China represents progress, there is a lack of effective options for patients following relapse. The promising results from TIVDAK, which demonstrated superior survival extension in patients whose disease progressed after initial treatments, including prior anti-PD(L)1 treatment, offer hope for addressing this critical unmet need.” In April 2024, the U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application (sBLA) granting full approval for TIVDAK® (tisotumab vedotin-tftv) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The approval was based on results from the global, randomized, Phase 3 innovaTV 301 clinical trial (NCT04697628), which met its primary endpoint, demonstrating overall survival (OS) benefit in adult patients with previously treated recurrent or metastatic cervical cancer treated with TIVDAK compared to chemotherapy. TIVDAK demonstrated a 30% reduction in the risk of death compared to chemotherapy (hazard ratio [HR]: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038)2. Median OS for patients treated with TIVDAK was 11.5 months [95% CI: 9.8-14.9] versus chemotherapy 9.5 months [95% CI: 7.9-10.7]. PFS and confirmed ORR were also significantly improved compared to chemotherapy. The safety profile of TIVDAK was consistent with its known safety profile as presented in the U.S. prescribing information, and no new safety signals were observed. Based on these encouraging results, Zai Lab intends to submit an NDA for TIVDAK to China’s National Medical Products Administration (NMPA) in the first quarter of 2025. The full China subpopulation data will be presented at a future medical conference in 2025. About innovaTV 301 Trial Design The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating TIVDAK® (tisotumab vedotin) versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) with recurrent or metastatic cervical cancer who received chemotherapy. Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate. The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov. About Cervical Cancer in China Cervical cancer remains one of the leading causes of cancer death in women in China and globally. An estimated 150,000 new cases of cervical cancer occur annually in China1. Current treatment options are limited for patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy. TIVDAK is well positioned to provide a new option for previously treated advanced cervical cancer patients who currently have limited treatment options and poor outcomes. About TIVDAK® (tisotumab vedotin) TIVDAK® (tisotumab vedotin) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. TIVDAK received accelerated approval from the FDA in September 2021 and full approval in April 2024 for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Please see full prescribing information, including BOXED WARNING for TIVDAK here. Zai Lab has an exclusive license from Seagen Inc., a company later acquired by Pfizer, to develop and commercialize TIVDAK in Greater China (mainland China, Hong Kong, Macau, and Taiwan, collectively). About Zai Lab Zai Lab (NASDAQ: ZLAB; HKEX: 9688) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, immunology, neuroscience and infectious disease. Our goal is to leverage our competencies and resources to positively impact human health worldwide. For additional information about Zai Lab, please visit www.zailaboratory.com or follow us at www.twitter.com/ZaiLab_Global. Zai Lab Forward-Looking Statements This press release contains forward-looking statements relating to our future expectations, plans, and prospects, including, without limitation, statements relating to our prospects and plans for developing and commercializing TIVDAK in Greater China, the potential benefits of TIVDAK, and the potential treatment of cervical cancer. These forward-looking statements may contain words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would,” and other similar expressions. Such statements constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not statements of historical fact or guarantees or assurances of future performance. Forward-looking statements are based on our expectations and assumptions as of the date of this press release and are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including but not limited to (1) our ability to successfully commercialize and generate revenue from our approved products, (2) our ability to obtain funding for our operations and business decisions, (3) the results of our clinical and pre-clinical development of our product candidates, (4) the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approvals of our product candidates, (5) risks related to doing business in China, and (6) other factors identified in our most recent annual and quarterly reports and in other reports we have filed with the U.S. Securities and Exchange Commission. We anticipate that subsequent events and developments will cause our expectations and assumptions to change, and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Our SEC filings can be found on our website at www.zailaboratory.com and the SEC’s website at www.sec.gov. Notes: 1 Bingfeng Han et al., "Cancer incidence and mortality in China, 2022" Journal of the National Cancer Center, 2024. DOI: 10.1016/j.jncc.2024.01.006. 2 The threshold for statistical significance is 0.0226 (2-sided). View source version on businesswire.com: https://www.businesswire.com/news/home/20250115437262/en/ Investor Relations: Christine Chiou / Lina Zhang +1 (917) 886-6929 / +86 136 8257 6943 christine.chiou1@zailaboratory.com / lina.zhang@zailaboratory.com Media: Shaun Maccoun / Xiaoyu Chen +1 (857) 270-8854 / +86 185 0015 5011 shaun.maccoun@zailaboratory.com / xiaoyu.chen@zailaboratory.com Source: Zai Lab Limited

Phase 3Clinical ResultDrug ApprovalLicense out/inImmunotherapy

27 Dec 2024

·www.pharmaceutical-technology.com

Eisbach Bio positions HRD-targeting therapy to supplant PARP inhibitors

Eisbach Bio is developing EIS-12656, which works by inhibiting ALC1 (chromodomain-helicase-DNA-binding protein 1-like), a chromatin remodeller and DNA helicase also involved in DNA repair. Image credit: Shutterstock/PeopleImages.com – Yuri A Eisbach Bio plans to use a $4.75m grant to advance EIS-12656, a small molecule ALC1 inhibitor to disrupt the genome structure in hard-to-treat cancer cells, says CEO Dr. Adrian Schomburg. Last month, the Martinsried, Germany-based biotech secured the funding from the Cancer Prevention and Research Institute of Texas (CRPIT) as part of the Texas Therapeutics Company Award. The company intends to direct the grant towards the ongoing Phase I/II MATCH trial (NCT06525298) of EIS-12656 in advanced, refractory solid tumours, as per the announcement. Schomburg said Eisbach views EIS-12656 as an alternative to poly-ADP-ribose polymerase inhibitors (PARP) inhibitors in therapy for many hard-to-treat cancers. PARP proteins are involved in DNA repair, and their targeted inhibition can hinder the proliferation of tumour cells. However, Schomburg notes, “there’s FDA scrutiny about the label of these inhibitors because of toxicity”. In September 2022, GSK voluntarily withdrew Zejula (niraparib) indication for treating advanced gynecological cancers in patients who had previously treated with three or more chemotherapy regimens and who had tumours that tested positive for homologous recombination deficiency (HRD). The withdrawal was due to updated information on the negative impact on overall survival seen in two studies with PARP inhibitors in that same setting. The mechanism of action for EIS-12656 is similar to PARP inhibitors, but it is one step further downstream, said Schomburg. The small molecule works by inhibiting ALC1 (chromodomain-helicase-DNA-binding protein 1-like), a chromatin remodeller and DNA helicase also involved in DNA repair. In what Schomburg terms a “’winner takes all’ market”, Eisbach believe their candidate can supplant PARP inhibitors as a less toxic option. Following IND approval in May 2024, EIS-12656 is currently being assessed as a monotherapy against HRD-positive tumours in the Phase I/II MATCH trial, and compared against a combination regimen of the drug with the PARP inhibitor olaparib, marketed as Lynparza by AstraZeneca, or trastuzumab deruxtecan, marketed by AstraZeneca and Daiichi Sankyo as Enhertu. Eisbach aims to initiate the Phase II portion of this study within Q2 2025. The company plans to focus on hard-to-treat indications, including ovarian, pancreatic, and prostate cancers, where long-term regimens mean high toxicity can be an especially limiting factor. Beyond these areas, Schomburg said Eisbach is interested in expanding EIS-12656 into lung cancers, colorectal cancers, and glioblastoma, utilising the drug’s blood-brain barrier penetrative qualities. These indications are also of particular interest for other helicase-targeting therapies, such as Accent Therapeutic’s DHX9 inhibitor ATX-559 , which is being studied in a Phase II trial (NCT06625515). Eisbach is developing other helicase-targeting therapies in preclinical studies, for which Schomburg stated IND-enabling trials are planned for 2025. He added that combination therapies, such as with antibody-drug conjugates where no combinatorial toxicity has been reported in preclinical models so far, are being considered.

Phase 2Drug Approval

20 Dec 2024

·pipelinereview.com

GSK announces FIRST trial met its primary endpoint of progression free survival in first line advanced ovarian cancer

LONDON, UK I December 20, 2024 I GSK plc (LSE/NYSE: GSK) today announced headline results from the FIRST-ENGOT-OV44 phase III trial evaluating Zejula (niraparib) and Jemperli (dostarlimab) in first line advanced ovarian cancer. The trial met its primary endpoint of PFS demonstrating a statistically significant difference with the addition of dostarlimab to both standard of care carboplatin-paclitaxel chemotherapy and niraparib maintenance, with or without bevacizumab. Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said : “As part of our focus in gynaecological cancers, we continue to evaluate the potential of this combination and look forward to sharing full results from the trial.” The key secondary endpoint of overall survival (OS) did not meet statistical significance. Further analyses are ongoing and data will be shared with health authorities and presented at an upcoming scientific meeting. The safety and tolerability profile was generally consistent with the known safety profiles of the individual agents. About ovarian cancer Ovarian cancer is the eighth most common cancer in women worldwide. 1 Despite high response rates to platinum-based chemotherapy in the first-line setting, approximately 85% of patients will experience disease recurrence. Once the disease recurs, it is rarely curable, with decreasing time intervals to each subsequent recurrence. 2 About the FIRST trial The FIRST-ENGOT-OV44 trial is an international, double-blind, randomised phase III ENGOT trial sponsored by GSK and led by GINECO, a French cooperative group dedicated to gynecological oncology. FIRST is investigating the addition of dostarlimab to both, standard of care (SOC) platinum-based chemotherapy and niraparib maintenance, with or without bevacizumab, as a first-line treatment of stage III or IV nonmucinous epithelial ovarian cancer. Originally, participants were randomised 1:1:2 into three groups: Arm 1: SOC chemotherapy followed by placebo maintenance; Arm 2: SOC chemotherapy followed by niraparib maintenance; Arm 3: SOC chemotherapy and dostarlimab followed by niraparib and dostarlimab maintenance. Bevacizumab could be added at the investigator’s discretion across all arms. Due to the approvals of PARP inhibitors in the first-line setting, Arm 1 (n=193) was closed and participants were subsequently randomized 1:2 to Arms 2 (n= 385) and 3 (n= 753) only. The primary endpoint is investigator-assessed PFS in Arms 2 and 3. Secondary endpoints include OS, PFS2, time to first and second subsequent therapy. ABOUT GINECO 3 GINECO (Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein) is the French Cooperative Group in Oncology labelled by INCa (Institut National du Cancer or French NCI) developing and conducting gynecological and metastatic breast cancer clinical trials at the national and international level. The GINECO group was founded in 1993 and is member of international consortia such as ENGOT and GCIG (Gynecologic Cancer InterGroup). About ENGOT 4 The European Network for Gynaecological Oncological Trial (ENGOT) groups is a research network of the European Society of Gynaecological Oncology and was founded in Berlin in October 2007. Currently, ENGOT consists of 21 trial groups from 31 European countries that perform cooperative clinical trials. ENGOT’s ultimate goal is to bring the best treatment to gynaecological cancer patients through the best science and enabling every patient in every European country to access a clinical trial. About Jemperli (dostarlimab) Jemperli , a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development prgramme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies for gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes. In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This includes patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) and dMMR/MSI-H tumours. Jemperli is also approved as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. Additionally, Jemperli is indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli , and cobolimab (GSK4069889), a TIM-3 antagonist. Important Information for Jemperli in the EU Indications Jemperli is indicated: Refer to the Jemperli EMA Reference information for a full list of adverse events and the complete important safety information in the EU. About Zejula (niraparib) Zejula is an oral, once-daily Poly (ADP-ribose) polymerase (PARP) inhibitor indicated in the US for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy; and for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy and who have been selected based on a US FDA-approved companion diagnostic for Zejula . Important Information for Zejula in the EU Indications Zejula is indicated: Refer to the Zejula EMA Reference Information for a full list of adverse events and the complete important safety information in the EU. GSK in oncology Oncology is an emerging therapeutic area for GSK where we are committed to maximising patient survival with a current focus on haematologic malignancies, gynaecologic cancers, and other solid tumours through breakthroughs in immuno-oncology and tumour-cell targeting therapies. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. References SOURCE: GlaxoSmithKline

Clinical ResultPhase 3License out/inDrug Approval

100 Deals associated with Niraparib Tosylate

External Link

KEGG	Wiki	ATC	Drug Bank
-	Niraparib Tosylate	L01XX54	DB11793

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Ovarian Cancer	CH	Tesaro, Inc.	03 Oct 2018
Peritoneal Neoplasms	CH	Tesaro, Inc.	03 Oct 2018
Ovarian Epithelial Carcinoma	IS	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Ovarian Epithelial Carcinoma	NO	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Ovarian Epithelial Carcinoma	LI	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Ovarian Epithelial Carcinoma	EU	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-sensitive epithelial ovarian cancer	EU	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-sensitive epithelial ovarian cancer	IS	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-sensitive epithelial ovarian cancer	NO	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-sensitive epithelial ovarian cancer	LI	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-Sensitive Fallopian Tube Carcinoma	EU	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-Sensitive Fallopian Tube Carcinoma	LI	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-Sensitive Fallopian Tube Carcinoma	NO	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-Sensitive Fallopian Tube Carcinoma	IS	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-Sensitive Primary Peritoneal Carcinoma	NO	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-Sensitive Primary Peritoneal Carcinoma	IS	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-Sensitive Primary Peritoneal Carcinoma	LI	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Platinum-Sensitive Primary Peritoneal Carcinoma	EU	GlaxoSmithKline (Ireland) Ltd.	16 Nov 2017
Fallopian Tube Carcinoma	US	GlaxoSmithKline LLC	27 Mar 2017
Primary peritoneal carcinoma	US	GlaxoSmithKline LLC	27 Mar 2017

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
BRCA Mutation Castration-Resistant Prostate Cancer	NDA/BLA	EU	GlaxoSmithKline (Ireland) Ltd.	27 Feb 2023
Platinum-Sensitive Ovarian Carcinoma	Phase 2	HU	Tesaro, Inc.	21 Jun 2013
Platinum-Sensitive Ovarian Carcinoma	Phase 2	DK	Tesaro, Inc.	21 Jun 2013
Platinum-Sensitive Ovarian Carcinoma	Phase 2	FR	Tesaro, Inc.	21 Jun 2013
Platinum-Sensitive Ovarian Carcinoma	Phase 2	DE	Tesaro, Inc.	21 Jun 2013
Platinum-Sensitive Ovarian Carcinoma	Phase 2	AT	Tesaro, Inc.	21 Jun 2013
Platinum-Sensitive Ovarian Carcinoma	Phase 2	GB	Tesaro, Inc.	21 Jun 2013
Ovarian Epithelial Carcinoma	Discovery	US	GlaxoSmithKline LLC	27 Mar 2017
Platinum-Sensitive Ovarian Carcinoma	Discovery	SE	Tesaro, Inc.	21 Jun 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03602859 (FIRST-ENGOT-OV44, PipelineReview) Manual	Phase 3	Ovarian Cancer First line	-	SOC + Placebo	(touveboflj) = The trial met its primary endpoint of PFS demonstrating a statistically significant difference with the addition of dostarlimab to both standard of care carboplatin-paclitaxel chemotherapy and niraparib maintenance, with or without bevacizumab. rhamqqlqmw (izxqveosrx ) Met View more	Positive	20 Dec 2024
				SOC + niraparib
NCT03752216 (NiQoLe, Pubmed \| JNCI Cancer Spectr)	Phase 4	Recurrent ovarian cancer Maintenance	139	Niraparib 200 mg/day	utysmermoq(xaqmbwycfj) = Physician-reported grade ≥3 niraparib-related AEs occurred in 24% of patients treated with Niraparib 200 mg/day rimtxuoecz (vvvmnimfqr ) View more	-	14 Dec 2024
NCT04986371 (RENI-1, ESMO_ASIA2024) Manual	Not Applicable	Ovarian Cancer Maintenance \| First line	227	Niraparib (ITT)	(srdcjzuqyb) = obooefealm rortxhvbzs (esncquszoo ) View more	Positive	07 Dec 2024
				Niraparib (BRCAm)	(srdcjzuqyb) = kyyksardpm rortxhvbzs (esncquszoo ) View more
NCT03207347 (Phase II Trial of the PARP Inhibitor, Niraparib, Pubmed \| JCO Precis Oncol)	Phase 2	mBAP1 \| ATM \| CHEK2 ... View more	37	Niraparib (Cohort A (histology-specific tumors likely to harbor mBAP1))	(wmtqjgjbcs) = tvokooczwk rkwihqirgm (kvwlbhkzqq, 1.0 - 9.2) View more	Negative	01 Dec 2024
NCT04915755 (ZEST, BusinessWire \| SABCS2024) Manual	Phase 3	Triple Negative Breast Cancer \| BRCA mutation positive Breast Cancer \| \|	40	Niraparib	(zzjibjblnj) = qrjawpdvta boqgzkioko (lshriyubxz )	Positive	25 Nov 2024
				Placebo	(zzjibjblnj) = sbljpjbblc boqgzkioko (lshriyubxz )
NCT05297864 (OU-SCC-PI-4G, CTgov)	Phase 2	Recurrent Glioma \| Recurrent Low Grade Astrocytoma \| Oligodendroglioma \| Recurrent Glioblastoma	15	Niraparib	rszeccgmeo(fcgsuruuiq) = azftcbvmnw jcynscjgyn (npbrgzzroj, daaxrgxowd - nkdggtfpju) View more	-	06 Nov 2024
NCT03326193 (COMB1NE, SGO2024)	Phase 2	Ovarian Epithelial Carcinoma First line homologous recombination (HR) proficient (HRp) \| undefined HR status (HRunk)	105	Niraparib + Bevacizumab	(vyllatbisn) = sgzjzikwts wvcrjpxdcf (lycecmmzdq, 16.5 - 25.1)	Positive	01 Nov 2024
				niraparib (Homologous recombination proficient (HRp) EOC)	(vyllatbisn) = vojzfolrzi wvcrjpxdcf (lycecmmzdq, 8.6 - 16.8)
NCT04546373 (GEICO-88R, ESMO2024) Manual	Not Applicable	Platinum-Sensitive Ovarian Carcinoma Maintenance BRCAwt	61	Niraparib 300 mg/day (FSD)	(cgddzntybd) = dgpyzmuelv amrtfdhkpz (bqgpnyiusr, 28.8 - NA) View more	Positive	14 Sep 2024
NCT02655016 (PRIMA \| ENGOT-OV26 \| GOG-3012, ESMO2024) Manual	Phase 3	Ovarian Cancer First line \| Maintenance homologous recombination-deficient	733	niraparib	(zhhwbaonez) = qacmzwzvko ompuwkiqhw (kutsfnzhiu ) View more	Positive	14 Sep 2024
				Plaebo	(zhhwbaonez) = usoilkogbr ompuwkiqhw (kutsfnzhiu ) View more
NCT03925350 (ESMO2024) Manual	Phase 2	Melanoma ARID1A/B \| ARID2 \| ATM ... View more	14	Niraparib 300 mg	(iwpdrwykfw) = There were no unexpected adverse events associated with niraparibe treatment tjoslojywx (bebneoraev )	Positive	14 Sep 2024
				Niraparib 300 mg (non-uveal melanoma)

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