A phase I trial of CT900, a novel α-folate receptor-mediated thymidylate synthase inhibitor, with expansion cohorts in patients with high grade serous ovarian cancer

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, Edward, Minchom, Anna, Lopez, Juanita, de Bono, Johann, Jones, Robert ORCID: https://orcid.org/0000-0003-3576-9496, Hall, Emma, Cook, Natalie, Basu, Bristi and Banerji, Udai 2022. A phase I trial of CT900, a novel α-folate receptor-mediated thymidylate synthase inhibitor, with expansion cohorts in patients with high grade serous ovarian cancer. Clinical Cancer Research 22 , 1268. 10.1158/1078-0432.CCR-22-1268

Full text not available from this repository.

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 tumours. 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 (HGSOC) 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, diarrhoea, cough, anaemia and pneumonitis, which were predominantly grade 1 and grade 2. Levels of CT900 greater than 600 nM 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 tumour 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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine European Cancer Stem Cell Research Institute (ECSCRI)
Additional Information:	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License .
Publisher:	American Association for Cancer Research
ISSN:	1078-0432
Date of First Compliant Deposit:	9 September 2022
Date of Acceptance:	17 August 2022
Last Modified:	22 Jun 2023 09:59
URI:	https://orca.cardiff.ac.uk/id/eprint/152429

Citation Data

Cited 2 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item