dc.contributor.author | Banerjee, S | |
dc.contributor.author | Michalarea, V | |
dc.contributor.author | Ang, JE | |
dc.contributor.author | Ingles Garces, A | |
dc.contributor.author | Biondo, A | |
dc.contributor.author | Funingana, I-G | |
dc.contributor.author | Little, M | |
dc.contributor.author | Ruddle, R | |
dc.contributor.author | Raynaud, F | |
dc.contributor.author | Riisnaes, R | |
dc.contributor.author | Gurel, B | |
dc.contributor.author | Chua, S | |
dc.contributor.author | Tunariu, N | |
dc.contributor.author | Porter, JC | |
dc.contributor.author | Prout, T | |
dc.contributor.author | Parmar, M | |
dc.contributor.author | Zachariou, A | |
dc.contributor.author | Turner, A | |
dc.contributor.author | Jenkins, B | |
dc.contributor.author | McIntosh, S | |
dc.contributor.author | Ainscow, E | |
dc.contributor.author | Minchom, A | |
dc.contributor.author | Lopez, J | |
dc.contributor.author | de Bono, J | |
dc.contributor.author | Jones, R | |
dc.contributor.author | Hall, E | |
dc.contributor.author | Cook, N | |
dc.contributor.author | Basu, B | |
dc.contributor.author | Banerji, U | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-09-06T10:40:24Z | |
dc.date.available | 2022-09-06T10:40:24Z | |
dc.date.issued | 2022-11-01 | |
dc.identifier | 708154 | |
dc.identifier.citation | Clinical Cancer Research, 2022, pp. CCR-22-1268 - | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5412 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-22-1268 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | CCR-22-1268 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.relation.ispartof | Clinical Cancer Research | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | 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. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-08-17 | |
dc.date.updated | 2022-09-06T10:28:24Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1158/1078-0432.CCR-22-1268 | |
rioxxterms.licenseref.startdate | 2022-08-19 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35984704 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/The Adult Drug Development Unit at the ICR and the RM | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/19/20 Starting Cohort | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Early Phase Drug Development | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1158/1078-0432.ccr-22-1268 | |
icr.researchteam | Clinical Pharma & Trials | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Adult DDU ICR & RM | |
icr.researchteam | Early Phase Drug Develop | |
icr.researchteam | PrCa Targeted Therapy | |
icr.researchteam | Clin Trials & Stats Unit | |
icr.researchteam | Clinical Pharmacology | |
dc.contributor.icrauthor | Ruddle, Ruth | |
dc.contributor.icrauthor | Raynaud, Florence | |
dc.contributor.icrauthor | Gurel, Bora | |
dc.contributor.icrauthor | Zachariou, Anna | |
dc.contributor.icrauthor | Minchom, Anna | |
dc.contributor.icrauthor | De Bono, Johann | |
dc.contributor.icrauthor | Hall, Emma | |
dc.contributor.icrauthor | Banerji, Udai | |
icr.provenance | Deposited by Dr Alvaro Ingles Russo on 2022-09-06. Deposit type is initial. No. of files: 1. Files: ccr-22-1268.pdf | |