دورية أكاديمية
A Phase I Trial of CT900, a Novel α-Folate Receptor-Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer.
| العنوان: | A Phase I Trial of CT900, a Novel α-Folate Receptor-Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer. |
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| المؤلفون: | Banerjee, Susana, Michalarea, Vasiliki, Ang, Joo Ern, Ingles Garces, Alvaro, Biondo, Andrea, Funingana, Ionut-Gabriel, Little, Martin, Ruddle, Ruth, Raynaud, Florence, Riisnaes, Ruth, Gurel, Bora, Chua, Sue, Tunariu, Nina, Porter, Joanna C, Prout, Toby, Parmar, Mona, Zachariou, Anna, Turner, Alison, Jenkins, Ben, McIntosh, Stuart, Ainscow, Ed, Minchom, Anna, Lopez, Juanita, de Bono, Johann, Jones, Robert, Hall, Emma, Cook, Natalie, Basu, Bristi, Banerji, Udai |
| بيانات النشر: | American Association for Cancer Research (AACR) |
| سنة النشر: | 2022 |
| المجموعة: | The University of Liverpool Repository |
| الوصف: | Purpose CT900 is a novel small molecule thymidylate synthase inhibitor that binds to α-folate receptor (α-FR) and thus is selectively taken up by α-FR-overexpressing tumors. Patients and methods A 3+3 dose escalation design was used. During dose escalation, CT900 doses of 1-6 mg/m2 weekly and 2-12 mg/m2 every 2 weeks (q2Wk) intravenously were evaluated. Patients with high-grade serous ovarian cancer were enrolled in the expansion cohorts. Results 109 patients were enrolled: 42 patients in the dose escalation and 67 patients in the expansion cohorts. At the dose/schedule of 12 mg/m2/q2Wk (with and without dexamethasone, n = 40), the most common treatment-related adverse events were fatigue, nausea, diarrhea, cough, anemia, and pneumonitis, which were predominantly grade 1 and grade 2. Levels of CT900 more than 600 nmol/L needed for growth inhibition in preclinical models were achieved for >65 hours at a dose of 12 mg/m2. In the expansion cohorts, the overall response rate (ORR), was 14/64 (21.9%). Thirty-eight response-evaluable patients in the expansion cohorts receiving 12 mg/m2/q2Wk had tumor evaluable for quantification of α-FR. Patients with high or medium expression had an objective response rate of 9/25 (36%) compared with 1/13 (7.7%) in patients with negative/very low or low expression of α-FR. Conclusions The dose of 12 mg/m2/q2Wk was declared the recommended phase II dose/schedule. At this dose/schedule, CT900 exhibited an acceptable side effect profile with clinical benefit in patients with high/medium α-FR expression and warrants further investigation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | Collapse authors list. Banerjee, Susana orcid:0000-0002-8840-7934 , Michalarea, Vasiliki orcid:0000-0002-3102-3534 , Ang, Joo Ern orcid:0000-0003-2103-996X , Ingles Garces, Alvaro orcid:0000-0002-0073-4237 , Biondo, Andrea orcid:0000-0003-0599-254X , Funingana, Ionut-Gabriel orcid:0000-0002-1197-2652 , Little, Martin orcid:0000-0003-2592-1570 , Ruddle, Ruth orcid:0000-0003-0025-8872 , Raynaud, Florence orcid:0000-0003-0957-6279 , Riisnaes, Ruth orcid:0000-0002-8924-302X et al (show 19 more authors) , Gurel, Bora orcid:0000-0002-5018-8078 , Chua, Sue orcid:0000-0001-5369-8156 , Tunariu, Nina orcid:0000-0001-6656-3699 , Porter, Joanna C orcid:0000-0002-7307-169X , Prout, Toby orcid:0000-0002-6465-4578 , Parmar, Mona orcid:0000-0001-7818-4100 , Zachariou, Anna orcid:0000-0002-7867-8327 , Turner, Alison orcid:0000-0003-2915-2756 , Jenkins, Ben orcid:0000-0002-2517-3595 , McIntosh, Stuart orcid:0000-0002-7379-4505 , Ainscow, Ed orcid:0000-0002-3119-8422 , Minchom, Anna orcid:0000-0002-9339-7101 , Lopez, Juanita orcid:0000-0001-8321-4212 , de Bono, Johann orcid:0000-0002-2034-595X , Jones, Robert orcid:0000-0001-5608-001X , Hall, Emma orcid:0000-0001-5999-5020 , Cook, Natalie orcid:0000-0003-2606-1082 , Basu, Bristi orcid:0000-0002-3562-2868 and Banerji, Udai orcid:0000-0003-1503-3123 (2022) A Phase I Trial of CT900, a Novel α-Folate Receptor-Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 28 (21). pp. 4634-4641. |
| DOI: | 10.1158/1078-0432.ccr-22-1268 |
| الإتاحة: | https://doi.org/10.1158/1078-0432.ccr-22-1268Test http://livrepository.liverpool.ac.uk/3171541Test/ |
| رقم الانضمام: | edsbas.89D8EFD2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/1078-0432.ccr-22-1268 |
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