Details

Autor(en) / Beteiligte

• Vestlev, Peter Michael
• Roest, Nicklas L.
• Schou, Jakob HV
• Stenvang, Jan
• Brünner, Nils

Titel

Abstract CT264: Clinical phase II study of SCO-101 - an inhibitor of SRPK1 and ABCG2 - restoring sensitivity to FOLFIRI in metastatic FOLFIRI resistant colorectal cancer patients

Ist Teil von

• Cancer research (Chicago, Ill.), 2020-08, Vol.80 (16_Supplement), p.CT264-CT264

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Abstract The purpose of the phase II study is to determine safety, tolerability, MTD and efficacy of SCO-101 in combination with FOLFIRI in patients with FOLFIRI resistant metastatic colorectal cancer. SCO-101 is a low molecular weight molecule (Acidic di-aryl urea). Preclinical studies have shown that it inhibits the SRPK1 kinase which phosphorylates and thereby activates proteins involved in the regulation of alternative splicing. It also degrades the ABCG2 drug efflux pump to which irinotecan (SN38) is a substrate. SCO-101 has successfully passed 4 clinical phase I studies in healthy volunteers and demonstrated to be a safe oral drug with very limited toxicity and good PK parameters. It reverses irinotecan- and several other types of anti-cancer drug resistance in in vitro and in vivo preclinical cancer models. The clinical phase II study: An open-label, non-randomized, prospective study, enrolling patients with acquired FOLFIRI resistant metastatic colorectal cancer. The study consists of two parts: -Part 1 is a dose escalation part based on a traditional 3+3 design. Increasing doses of SCO-101 are investigated in combination with a fixed, patient specific, dose of FOLFIRI. The primary objectives of part 1, is to determine the safety- and toxicity profile and the MTD of SCO-101. The MTD will be the recommended dose of SCO-101 for part 2 (RDP2); -Part 2 is the efficacy part, where up to 25 patients (Simons Two Stage Design) receive the SCO-101 RDP2 in combination with FOLFIRI. Primary objectives are to determine the safety- and toxicity profile and assess objective response rates. A number of potential biomarkers for SCO-101 efficacy will be evaluated. Approval for the study has been obtained and the study will start recruiting patients primo 2020. SCO-101 has two unique mechanisms of action. No other drugs have been presented that inhibits the SRPK1 kinase. Several published preclinical studies have associated high SRPK1 activity with progression of cancer including development of cancer drug resistance. SCO-101 is also the first drug described that degrades the ABCG2 drug efflux pump. If a positive signal is obtained in the clinical study, we will continue with a randomized clinical design allowing for time-dependent end-points, e.g. PFS and OS. Citation Format: Peter Michael Vestlev, Nicklas L. Roest, Jakob HV Schou, Jan Stenvang, Nils Brünner. Clinical phase II study of SCO-101 - an inhibitor of SRPK1 and ABCG2 - restoring sensitivity to FOLFIRI in metastatic FOLFIRI resistant colorectal cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT264.