A5009723460- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Neuroblastoma Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Cancer, Lipids, and Metabolism
- Cancer Treatment and Pharmacology
- Colorectal Cancer Treatments and Studies
- Prostate Cancer Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Hormonal and reproductive studies
- Lung Cancer Research Studies
- Cancer, Hypoxia, and Metabolism
- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Pancreatic and Hepatic Oncology Research
- Gastric Cancer Management and Outcomes
- Multiple Myeloma Research and Treatments
- Cancer therapeutics and mechanisms
- Renal cell carcinoma treatment
- Inflammatory mediators and NSAID effects
- Cancer-related gene regulation
- Glioma Diagnosis and Treatment
- Cell death mechanisms and regulation
- Synthesis and biological activity
Sunesis (United States)
2022-2024
Ignyta (United States)
2016-2022
Edison Pharmaceuticals (United States)
2014-2017
Tracon Pharmaceuticals (United States)
2015
Dana (United States)
2013
Memorial Sloan Kettering Cancer Center
2012-2013
Cornell University
2013
Institut Bergonié
2013
Taichung Veterans General Hospital
2013
Pfizer (United States)
2007-2012
Despite the impressive clinical activity of second-generation antiandrogens enzalutamide and ARN-509 in patients with prostate cancer, acquired resistance invariably emerges. To identify molecular mechanisms underlying resistance, we developed characterized cell lines resistant to enzalutamide. In a subset lines, exhibit agonist due missense mutation (F876L) ligand-binding domain androgen receptor (AR). AR F876L is sufficient confer vitro vivo models castration-resistant cancer (CRPC)....
BackgroundMammary analogue secretory carcinoma (MASC) is a recently described pathologic entity. We report the case of patient with an initial diagnosis salivary acinic cell later reclassified as MASC after next-generation sequencing revealed ETV6-NTRK3 fusion.Patients and methodsThis alteration was targeted pan-Trk inhibitor entrectinib (Ignyta), which possesses potent in vitro activity against lines containing various NTRK1/2/3 fusions.ResultsA dramatic durable response achieved this...
Purpose ARN-509 is a novel androgen receptor (AR) antagonist for the treatment of castration-resistant prostate cancer (CRPC). inhibits AR nuclear translocation and binding to response elements and, unlike bicalutamide, does not exhibit agonist properties in context overexpression. This first-in-human phase I study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, antitumor activity men with metastatic CRPC. Patients Methods Thirty patients progressive CRPC received...
Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors ROS1 non–small-cell lung cancer. We report an analysis STARTRK-NG trial, investigating recommended phase 2 dose (RP2D) activity entrectinib in pediatric patients including primary central nervous system tumors. (NCT02650401) 1/2 trial. Phase 1, dose-escalation oral, once-daily entrectinib, enrolled <22 with/without target...
Sunitinib has demonstrated antitumor activity in metastatic renal cell carcinoma (mRCC) when given at 50 mg/d on a 4-weeks-on 2-weeks-off regimen. Herein, we report results of an open-label, multicenter phase II mRCC study sunitinib administered continuous once-daily dosing regimen.Eligibility criteria included histologically proven with measurable disease, failure one prior cytokine regimen, and good performance status. Patients were randomly assigned to starting dose 37.5 the morning (AM)...
We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC).Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary points included progression-free (PFS). Two interim analyses planned.Overall, 873 patients (n =...
Apalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents nuclear translocation, DNA binding, transcription of gene targets. To evaluate activity safety apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). We conducted multicenter phase 2 study nmCRPC high risk for progression (prostate-specific antigen [PSA] ≥8 ng/ml or PSA doubling time [PSA DT] ≤10 mo). Patients received 240 mg/d while...
Purpose: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients progressive metastatic castration-resistant prostate cancer (mCRPC).Experimental Design: Two cohorts were studied: AAP-naïve post-AAP who had received ≥6 months AAP. Patients mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All 240 mg/day. Primary endpoint was ≥50% decline 12-week PSA according to Prostate...
10009 Background: Entrectinib is a CNS-penetrant oral inhibitor of TrkA/B/C, ROS1 and ALK tyrosine kinases. We report the efficacy entrectinib in children with recurrent/refractory solid or CNS tumors. Methods: Patients ≤ 20y old tumors were eligible. After determination recommended dose all-comers, disease-specific expansion cohorts harboring target aberrations NTRK1/2/3, ALK, neuroblastoma (NBL), regardless mutation spectrum, enrolled. Response, assessed by Investigator, was classified as...
Abstract Purpose: Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 potent and selective orally-bioavailable GR antagonist. Patients Methods: Safety, pharmacokinetic/pharmacodynamic, antitumor activity combination with enzalutamide were studied patients mCRPC progressing on enzalutamide. doses ranging from 80 240 mg once daily tested 160 daily....
Abstract Glioneuronal tumors constitute a histologically diverse group of primary central nervous system neoplasms that are typically slow-growing and managed conservatively. Genetic alterations associated with glioneuronal include BRAF mutations oncogenic fusions. To further characterize this tumors, we collected cohort 26 performed in-depth genomic analysis. We identified in (34%) fusions (30%), consistent previously published reports. In addition, discovered novel involving members the...
4515 Background: Options for treatment of men with mCRPC after progression on docetaxel-based chemotherapy are limited. SU is a multitargeted inhibitor VEGFR and PDGFR that showed antitumor activity in phase II trials advanced (Sonpavde; Michaelson; Zurita, 2009). Here, we report results III trial SU+P progressive chemotherapy. Methods: In this multicenter, double-blind study, eligible were stratified by ECOG performance status type (PSA or radiographic) randomized (2:1) to receive P 5 mg...
Despite advances in genomic analysis, the molecular origin of neuroendocrine tumors (NETs) is complex and poorly explained by described oncogenes. The neurotrophic TRK family, including NTRK1, 2, 3, encode proteins TRKA, TRKB, TRKC, respectively, involved normal nerve development. Because NETs develop from diffuse system, we sought to determine whether NTRK alterations occur TRK-targeted therapy would be effective. A patient with metastatic well-differentiated NET, likely small intestine,...
521 Background: Despite recent improvements in chemotherapy for pancreatic cancer that have demonstrated survival, response rates remain at less than 50%. Distinct molecular subgroups of harbor specific actionable alterations recently been identified. These include gene fusions the receptor tyrosine kinases NTRK and ROS1. Entrectinib is a CNS-active, potent, selective TRK ROS1 inhibitor has shown substantial clinical activity patients with locally advanced or metastatic solid tumors (Drilon...
GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent (ER)-mediated signaling.A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or luteinizing hormone-releasing hormone, expansion study determined the safety, pharmacokinetics, recommended 2 (RP2D) of in postmenopausal women ER + (HER2 -) locally advanced metastatic breast cancer (MBC). Baseline...
48 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion multicenter I/II study evaluating activity in 3 distinct patient populations men with CRPC: 1) non-metastatic treatment-naïve CRPC; 2) mCRPC (tx-naïve); 3) abiraterone acetate pre-treated (AA). Preliminary results for 2 cohorts patients metastatic CRPC are presented here. Methods: All had...
Abstract Background: Entrectinib is a potent oral inhibitor of the tyrosine kinases TrkA, TrkB, TrkC (encoded by genes NTRK1, NTRK2, NTRK3, respectively), ROS1, and ALK with IC50 &lt; 2 nM (biochemical kinase assay). It has been evaluated in two Phase 1 studies (STARTRK-1 ALKA-372-001) patients advanced or metastatic solid tumors harboring NTRK1/2/3, molecular alterations, without asymptomatic controlled CNS disease. Previously, we reported 600 mg daily as Recommended Dose (RP2D) an...
7 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion multicenter I/II study evaluating activity in 3 distinct patient populations men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naïve progressive disease after abiraterone acetate). Preliminary results for cohort patients high-risk are presented here. Methods: All had no...
Abstract First generation inhibitors of PRC2 (Polycomb Repressive Complex 2) targeting EZH2 (Enhancer Zeste Homolog achieved clinical proof-of-concept in follicular lymphoma and epithelioid sarcoma, emerging data recently revealed promising activity prostate cancer combination with AR pathway (ARPIs). Here we describe the discovery development a second inhibitor, ORIC-944, potent, selective, allosteric inhibitor that binds EED (Embryonic Ectoderm Development) subunit within complex....
43 Background: In CRPC, androgen receptor (AR) overexpression is associated with resistance to first-generation anti-androgen therapy such as bicalutamide. ARN-509 a novel small molecule AR antagonist that impairs nuclear translocation and binding DNA, inhibiting tumor growth promoting apoptosis, no partial agonist activity. Preclinical data shows binds 5-fold greater affinity than bicalutamide, induces regression in hormone-sensitive CRPC xenograft models. Methods: this open-label, Phase...