scholarly journals Alpha-Folate Receptor-targeting Thymidylate Synthase Inhibitor ONX-0801

2020 ◽  
Author(s):  
Keyword(s):  
Thymidylate Synthase ◽  
Folate Receptor ◽  
Receptor Targeting ◽  
Thymidylate Synthase Inhibitor ◽  
Folate Receptor Targeting ◽  
Synthase Inhibitor

scholarly journals BGC 945, a Novel Tumor-Selective Thymidylate Synthase Inhibitor Targeted to α-Folate Receptor–Overexpressing Tumors

2005 ◽  
Vol 65 (24) ◽  
pp. 11721-11728 ◽  
Author(s):  
David D. Gibbs ◽  
Davinder S. Theti ◽  
Nadya Wood ◽  
Matthew Green ◽  
Florence Raynaud ◽  
...  
Keyword(s):  
Thymidylate Synthase ◽  
Folate Receptor ◽  
Thymidylate Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Tumor Selective

scholarly journals Imaging Pharmacodynamics of the α-Folate Receptor–Targeted Thymidylate Synthase Inhibitor BGC 945

2008 ◽  
Vol 68 (10) ◽  
pp. 3827-3834 ◽  
Author(s):  
Radhakrishna G. Pillai ◽  
Martin Forster ◽  
Meg Perumal ◽  
Fraser Mitchell ◽  
Julius Leyton ◽  
...  
Keyword(s):  
Thymidylate Synthase ◽  
Folate Receptor ◽  
Thymidylate Synthase Inhibitor ◽  
Synthase Inhibitor

An investigator-initiated phase I study of ONX-0801, a first-in-class alpha folate receptor targeted, small molecule thymidylate synthase inhibitor in solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2503-2503 ◽  
Author(s):  
Udai Banerji ◽  
Alvaro Henrique Ingles Garces ◽  
Vasiliki Michalarea ◽  
Ruth Ruddle ◽  
Florence I. Raynaud ◽  
...  
Keyword(s):  
Phase Ii ◽  
Thymidylate Synthase ◽  
Dose Escalation ◽  
Folate Receptor ◽  
Phase Ii Trials ◽  
Suspected Drug ◽  
Thymidylate Synthase Inhibitor ◽  
Expansion Cohort ◽  
Synthase Inhibitor ◽  
Dose Limiting Toxicity

2503 Background: ONX-0801 is a first-in-class alpha folate receptor (AFR) targeted thymidylate synthase inhibitor, engineered to differentially accumulate 6000-fold in AFR overexpressing cancer cells. Methods: A 3+3 dose escalation design was used and two IV schedules were explored. Schedule A, weekly dosing (QW) and schedule B, once every 2 weeks dosing (Q2W). A cycle consisted of 4 weeks and treatment was stopped after 6 cycles in both schedules. An expansion cohort to evaluate clinical activity in patients with AFR overexpressing high grade serous ovarian cancer (HGSOC) was planned. Results: 21 patients each were treated in schedule A and B exploring doses ranging from 1-6 mg/m2 and 2-12 mg/m2, respectively. The dose limiting toxicity on schedule A was G3 cellulitis; no dose limiting toxicity was seen on schedule B. The most common toxicities were fatigue 15/42 (36%), nausea 9/42 (21%) and dysgeusia 5/42 (12%). Within schedule A at 4 mg/m2, 2 patients developed suspected drug-related changes on pulmonary function tests (drop in Dlco > 15%) at cycles 5 and 6, respectively. No cases of suspected drug-related drop in Dlco were noted in patients treated in schedule B. No grade 3-4 diarrhea, mucositis or neutropenia were seen in either cohort. The Cmax, AUC and half-life at 12 mg/m2 were 4952 ng/mL, 85170 h*ng/mL and 26 h, respectively. Pre-clinical PK-PD modelling aimed to achieve concentrations between 0.05-1 µM and this was achieved for periods of 48 h at doses of 4 mg/m2and above. Based on safety and PK, the recommended phase II dose (RP2D) of ONX-0801 was 12 mg/m2 Q2W and an expansion in patients with HGSOC is ongoing. 5 patients with HGSOC had partial responses (PRs) in the dose escalation cohort. In the current expansion cohort in patients with HGSOC, 5/11 patients had PRs. Archival samples have been analyzed from 8/11 patients in the expansion cohort. 4/4 AFR+ve and 4/4 AFR-ve patients did and did not have a PR following treatment with ONX-0801, respectively. Conclusions: The RP2D of ONX-0801 is 12 mg/m2 Q2W. At the RP2D, multiple patients with AFR overexpressing HGSOC have had PRs and further randomized biomarker prespecified phase II trials are warranted. Clinical trial information: NCT02360345.

scholarly journals Phase I, Pharmacokinetic and Biological Correlative Study of OSI-7904L, a Novel Liposomal Thymidylate Synthase Inhibitor, and Cisplatin in Patients with Solid Tumors

2008 ◽  
Vol 14 (23) ◽  
pp. 7947-7955 ◽  
Author(s):  
Alejandro D. Ricart ◽  
Jordan D. Berlin ◽  
Kyriakos P. Papadopoulos ◽  
Samira Syed ◽  
Daniel W. Drolet ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Thymidylate Synthase ◽  
Correlative Study ◽  
Thymidylate Synthase Inhibitor ◽  
Synthase Inhibitor

scholarly journals Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis

2017 ◽  
Vol Volume 12 ◽  
pp. 6735-6746 ◽  
Author(s):  
Jinlong Zhao ◽  
Menghui Zhao ◽  
Changhui Yu ◽  
Xueyan Zhang ◽  
Jiaxin Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Folate Receptor ◽  
Ph Responsive ◽  
Receptor Targeting ◽  
Folate Receptor Targeting

Radiosynthesis and Preclinical Evaluation of 3′-Aza-2′-[18F]fluorofolic Acid: A Novel PET Radiotracer for Folate Receptor Targeting

2013 ◽  
Vol 24 (2) ◽  
pp. 205-214 ◽  
Author(s):  
Thomas Betzel ◽  
Cristina Müller ◽  
Viola Groehn ◽  
Adrienne Müller ◽  
Josefine Reber ◽  
...  
Keyword(s):  
Folate Receptor ◽  
Receptor Targeting ◽  
Preclinical Evaluation ◽  
Folate Receptor Targeting

scholarly journals Tumor imaging using P866, a high-relaxivity gadolinium chelate designed for folate receptor targeting

2008 ◽  
Vol 60 (6) ◽  
pp. 1337-1346 ◽  
Author(s):  
Claire Corot ◽  
Philippe Robert ◽  
Eric Lancelot ◽  
Philippe Prigent ◽  
Sébastien Ballet ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Folate Receptor ◽  
Receptor Targeting ◽  
Gadolinium Chelate ◽  
High Relaxivity ◽  
Folate Receptor Targeting
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