Delving into the Latest Updates on Clovis Oncology UK Ltd. with Synapse

概览

疾病领域	数量

内分泌与代谢疾病	1
肿瘤	1

排名前五的药物类型	数量

小分子化药	1

排名前五的靶点	数量

PARP1 x PARP2 x PARP3	1

关联

1

项与 Clovis Oncology UK Ltd. 相关的药物

Rucaparib Camsylate

芦卡帕利

靶点

PARP1 x PARP2 x PARP3

作用机制

PARP1抑制剂 [+2]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2016-12-19

100 项与 Clovis Oncology UK Ltd. 相关的临床结果

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0 项与 Clovis Oncology UK Ltd. 相关的专利（医药）

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17

项与 Clovis Oncology UK Ltd. 相关的文献（医药）

2023-09-01·European Urology

Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study

Article

作者: Watkins, Simon P ; Go, Jowell ; Font, Albert ; Piulats, Josep M ; Ryan, Charles J ; Shapiro, Jeremy ; Campbell, David ; McDermott, Ray ; Spaeth, Dominique ; Pintus, Elias ; Patnaik, Akash ; Dowson, Melanie ; Castellano, Daniel ; Bambury, Richard M ; Burke, John M ; Simmons, Andrew D ; Merseburger, Axel S ; Hardy-Bessard, Anne-Claire ; Voog, Eric ; Heidenreich, Axel ; Zhang, Jingsong ; Fizazi, Karim ; Abida, Wassim ; Chowdhury, Simon ; Despain, Darrin ; Daugaard, Gedske ; Ganju, Vinod ; Bryce, Alan H ; Sautois, Brieuc ; Loehr, Andrea

BACKGROUNDInitial TRITON2 (NCT02952534) results demonstrated the efficacy of rucaparib 600 mg BID in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with a BRCA1 or BRCA2 (BRCA) or other DNA damage repair (DDR) gene alteration.OBJECTIVETo present the final data from TRITON2.DESIGN, SETTING, AND PARTICIPANTSTRITON2 enrolled patients with mCRPC who had progressed on one or two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSISThe primary endpoint was objective response rate (ORR; as per the modified Response Evaluation Criteria in Solid Tumor Version 1.1/Prostate Cancer Clinical Trials Working Group 3 criteria in patients with measurable disease by independent radiology review [IRR]); prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) was a key secondary endpoint.RESULTS AND LIMITATIONSAs of July 27, 2021 (study closure), TRITON2 had enrolled 277 patients, grouped by mutated gene: BRCA (n = 172), ATM (n = 59), CDK12 (n = 15), CHEK2 (n = 7), PALB2 (n = 11), or other DDR gene (Other; n = 13). ORR by IRR was 46% (37/81) in the BRCA subgroup (95% confidence interval [CI], 35-57%), 100% (4/4) in the PALB2 subgroup (95% CI, 40-100%), and 25% (3/12) in the Other subgroup (95% CI, 5.5-57%). No patients within the ATM, CDK12, or CHEK2 subgroups had an objective response by IRR. PSA50 response rates (95% CI) in the BRCA, PALB2, ATM, CDK12, CHEK2, and Other subgroups were 53% (46-61%), 55% (23-83%), 3.4% (0.4-12), 6.7% (0.2-32%), 14% (0.4-58%), and 23% (5.0-54%), respectively.CONCLUSIONSThe final TRITON2 results confirm the clinical benefit and manageable safety profile of rucaparib in patients with mCRPC, including those with an alteration in BRCA or select non-BRCA DDR gene.PATIENT SUMMARYAlmost half of TRITON2 patients with BRCA-mutated metastatic castration-resistant prostate cancer had a complete or partial tumor size reduction with rucaparib; clinical benefits were also observed with other DNA damage repair gene alterations.

2023-02-20·Journal of Clinical Oncology

Rucaparib for metastatic castration-resistant prostate cancer (mCRPC): TRITON3 interim overall survival and efficacy of rucaparib vs docetaxel or second-generation androgen pathway inhibitor therapy.

作者: Loehr, Andrea ; Chowdhury, Simon ; Ryan, Charles J. ; Reaume, M. Neil ; Heidenreich, Axel ; Fizazi, Karim ; Sautois, Brieuc ; McDermott, Raymond S. ; Pintus, Elias ; Abida, Wassim ; Sridhar, Srikala S. ; Watkins, Simon Paul ; Go, Jowell ; Daugaard, Gedske ; Bryce, Alan Haruo ; Despain, Darrin ; Gingerich, Joel Roger ; Ostler, Peter James ; Krieger, Laurence E. M. ; Piulats, Josep M.

18 Background: TRITON3 (NCT02975934) is a randomized, multicenter, open-label, phase 3 study of rucaparib vs physician’s choice (docetaxel [DTX], abiraterone [ABI] or enzalutamide [ENZ]) in patients (pts) with chemotherapy-naïve mCRPC with BRCA1/2 (BRCA) or ATM alterations. It was previously reported that rucaparib significantly improved the primary endpoint of radiographic progression-free survival (rPFS) vs physician’s choice in pts with BRCA or ATM alterations. We report here the interim overall survival (OS) and also report on efficacy of rucaparib compared individually with either DTX or ABI/ENZ. Methods: Pts had disease progression after 1 prior second-generation androgen pathway inhibitor therapy in any setting and were randomized 2:1 to rucaparib 600 mg BID or physician’s choice of DTX, ABI or ENZ. An ordered step-down multiple comparisons procedure was used to control the overall error rate. OS was a key secondary endpoint with rPFS as the primary endpoint tested first in the BRCA subgroup, then the intent-to-treat (ITT) population. Subgroup analyses based on physician’s choice were exploratory. Results: As of August 25, 2022, 302 pts with BRCA and 103 pts with ATM alterations were randomized. OS maturity was 54% in the BRCA subgroup and 59% in the ITT population. rPFS and OS are shown. The most frequent treatment-emergent adverse event (TEAE) in the rucaparib, DTX and ABI/ENZ groups was asthenia/fatigue (61.1%, 67.6% and 57.6%, respectively). The most frequent grade ≥3 TEAE in the rucaparib, DTX and ABI/ENZ groups was anemia (23.7%), neutropenia (14.1%), and hypertension (10.2%), respectively. Conclusions: Rucaparib significantly improved rPFS vs either DTX or ABI/ENZ; safety was consistent with prior reports. Interim OS results suggest a trend towards improvement for rucaparib vs DTX or ABI/ENZ in pts with mCRPC and BRCA alterations. Clinical trial information: NCT02975934 . [Table: see text]

2022-09-01·European Journal of Drug Metabolism and Pharmacokinetics

Population Pharmacokinetic Modeling of Lucitanib in Patients with Advanced Cancer

Article

作者: Wride, Kenton ; Lepley, Denise ; Liao, Mingxiang ; Sale, Mark ; Cameron, Terri ; Zhou, Jie ; Xiao, Jim

BACKGROUNDLucitanib is an oral, potent, selective inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1‒3, fibroblast growth factor receptors 1‒3, and platelet-derived growth factor receptors alpha/beta.OBJECTIVEWe aimed to develop a population pharmacokinetics (PopPK) model for lucitanib in patients with advanced cancers.METHODSPopPK analyses were based on intensive and sparse oral pharmacokinetic data from 5 phase 1/2 clinical studies of lucitanib in a total of 403 patients with advanced cancers. Lucitanib was administered at 5‒30 mg daily doses as 1 of 2 immediate-release oral formulations: a film-coated tablet or a hard gelatin capsule.RESULTSLucitanib pharmacokinetics were best described by a 2-compartment model with zero-order release into the dosing compartment, followed by first-order absorption and first-order elimination. Large between-subject pharmacokinetic variability was partially explained by body weight. No effects of demographics or tumor type on lucitanib pharmacokinetics were observed. The model suggested that the formulation impacted release duration (tablet, 0.243 h; capsule, 0.814 h), but the effect was not considered clinically meaningful. No statistically significant effects were detected for concomitant cytochrome P450 (CYP) 3A4 inhibitors or inducers, CYP2C8 or P-glycoprotein inhibitors, serum albumin, mild/moderate renal impairment, or mild hepatic impairment. Concomitant proton pump inhibitors had no clinically significant effect on lucitanib absorption.CONCLUSIONSThe PopPK model adequately described lucitanib pharmacokinetics. High between-subject pharmacokinetic variability supports a safety-based dose-titration strategy currently being used in an ongoing clinical study of lucitanib to optimize drug exposure and clinical benefit.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT01283945, NCT02053636, ISRCTN23201971, NCT02202746, NCT02109016.

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100 项与 Clovis Oncology UK Ltd. 相关的转化医学

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