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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Date
2022-11-01ICR Author
Author
Banerjee, S
Michalarea, V
Ang, JE
Ingles Garces, A
Biondo, A
Funingana, I-G
Little, M
Ruddle, R
Raynaud, F
Riisnaes, R
Gurel, B
Chua, S
Tunariu, N
Porter, JC
Prout, T
Parmar, M
Zachariou, A
Turner, A
Jenkins, B
McIntosh, S
Ainscow, E
Minchom, A
Lopez, J
de Bono, J
Jones, R
Hall, E
Cook, N
Basu, B
Banerji, U
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Research team
Clinical Pharma & Trials
Cancer Biomarkers
Adult DDU ICR & RM
Early Phase Drug Develop
PrCa Targeted Therapy
Clin Trials & Stats Unit
Clinical Pharmacology
Language
eng
Date accepted
2022-08-17
License start date
2022-08-19
Citation
Clinical Cancer Research, 2022, pp. CCR-22-1268 -
Publisher
AMER ASSOC CANCER RESEARCH