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E-Poster Display

605TiP - Targeting anti-cancer drug resistance in gastro-intestinal cancer: Inhibition of the SRPK1 kinase and degradation of the ABCG2 drug efflux pump

Date

17 Sep 2020

Session

E-Poster Display

Topics

Clinical Research

Tumour Site

Presenters

Morten Ladekarl

Citation

Annals of Oncology (2020) 31 (suppl_4): S462-S504. 10.1016/annonc/annonc271

Authors

M. Ladekarl1, J.H.V. Schou2, N.L. Roest3, J. Stenvang3, N. Brünner4, P.M. Vestlev3

Author affiliations

  • 1 Dept. Of Oncology, Clinical Cancer Research Center And Dept. Of Clinical Medicine, Aalborg University Hospital and Aalborg University, 9000 - Aalborg/DK
  • 2 Dept. Of Oncology, Herlev-Gentofte Hospital, Copenhagen/DK
  • 3 Scandion Oncology, Scandion Oncology, Copenhagen/DK
  • 4 Institute Of Drug Design And Pharmacology, University of Copenhagen, Copenhagen/DK

Resources

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Abstract 605TiP

Background

Resistance to anti-cancer drugs is a frequent event and represents one of the most important problems to be solved in oncology. Scandion Oncology and clinical partners have initiated an open labelled non-randomized first clinical phase II study (NCT04247256) with the drug SCO-101, which is a safe oral drug that inhibits the SRPK1 kinase and degrades the ABCG2 drug efflux pumps. Both of these proteins are involved in anti-cancer drug resistance. SRPK1 regulates alternative gene splicing and ABCG2 pumps certain types of chemotherapy out of cells. Preclinical experiments have shown that SCO-101 reverses cancer cell resistance to irinotecan and to taxanes.

Trial design

In the ongoing clinical study, up to 50 patients with metastatic colorectal cancer and with acquired FOLFIRI resistance, continue FOLFIRI but now in combination with SCO-101. Primary end-points are safety, toxicity and objective response rates. A second clinical dose finding study including advanced or metastatic pancreatic cancer patients to receive 1st line nab-paclitaxel and gemcitabine plus SCO-101 will be initiated in Q3, 2020 and is planned to be followed by a randomized phase II trial. In this study patients are to receive 1st line nab-paclitaxel and gemcitabine +/- SCO-101. The study has safety, toxicity and progression-free survival as primary end-points. With a positive result, additional patients will be enrolled. Both of the clinical studies will be initiated with a run-in phase where SCO-101 is dose escalated while the dose of chemotherapy will be constant. SCO-101 will be taken at home daily 4 days before chemotherapy. Biopsies will be analyzed for potential biomarkers and these will be associated with patient outcome in a post-treatment analysis.

Clinical trial identification

NCT04247256.

Editorial acknowledgement

Legal entity responsible for the study

Scandion Oncology.

Funding

Scandion Oncology.

Disclosure

M. Ladekarl: Research grant/Funding (institution): Scandion Oncology. J.H.V. Schou: Research grant/Funding (institution): Scandion Oncology. N.L. Roest: Shareholder/Stockholder/Stock options, Full/Part-time employment: Scandion Oncolocy. J. Stenvang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Scandion Oncology. N. Brünner: Shareholder/Stockholder/Stock options, Full/Part-time employment: Scandion Oncology. P.M. Vestlev: Shareholder/Stockholder/Stock options, Full/Part-time employment: Scandion Oncology.

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