Abstract 5049
Background
Small cell lung cancer (SCLC), a fast growing and aggressive neuroendocrine malignancy, shows a dismal prognosis with the current pharmacopeia. Notch is a tumor suppressor repressed in SCLC. Iadademstat (ORY-1001) is the leading selective LSD1 inhibitor and has been shown to re-activate the NOTCH pathway in SCLC, resulting in the repression of ASCL1, a well-known non-druggable SCLC tumor driver, and to produce robust, and in some cases complete and durable, tumor regression in some chemoresistant PDX models. In a previous phase I study in acute leukemia, iadademstat was safe and well tolerated, supporting it is a meaningful candidate for combination therapy with other agents. This is the first combo clinical trial in SCLC with a LSD1 inhibitor and the current chemotherapeutic treatments.
Trial design
CLEPSIDRA (EudraCT nº 2018-000469-35) is an ongoing phase II study of iadademstat in combination with platinum plus etoposide in patients with relapsed extensive stage SCLC who are candidate to re-challenge chemotherapy. To increase likelihood of response to iadademstat treatment, inclusion of patients requires confirmation of positive expression to iadademstat candidate predictive biomarkers in archival primary tumor tissue or in metastatic tissue samples. This clinical trial is an open label single-arm multicenter study to assess for the first time the safety, tolerability, dose finding and efficacy of iadademstat in combination with chemotherapy in SCLC patients. The study is composed of a dose/regime finding phase aimed to establish the recommended dose and regime of the combination, and a second phase to assess clinical activity of the combination including tumor response according RECIST criteria version 1.1, duration of response, time to progression, time to response, objective response, progression-free survival and overall survival. It is planned to enroll up to 36 patients. The first patient was included November 2018 and the last-patient-in is expected by Q1 2020.
Clinical trial identification
EudraCT nº 2018-000469-35. Approval date: 10/10/2018.
Editorial acknowledgement
Legal entity responsible for the study
Oryzon Genomics SA.
Funding
Oryzon Genomics SA.
Disclosure
A.F. Navarro Mendivil: Honoraria (self), Advisory / Consultancy, member Safety Monitoring Committee: Oryzon Genomics SA; Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca. S. Gutierrez: Full / Part-time employment: Oryzon Genomics SA. T. Maes: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Oryzon Genomics SA; Officer / Board of Directors: Mendelion Lifesciences. R. Bullock: Full / Part-time employment, Officer / Board of Directors: Oryzon Genomics SA. M. Ropacki: Full / Part-time employment: Oryzon Genomics SA. C. Buesa: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Oryzon Genomics SA.
Resources from the same session
5939 - Matrix metalloproteinases and their tissue inhibitors genes abnormal DNA methylation in breast cancer
Presenter: Olga Simonova
Session: Poster Display session 1
Resources:
Abstract
2703 - Uveal melanoma cell lines depend on multiple signaling pathways for survival
Presenter: John Park
Session: Poster Display session 1
Resources:
Abstract
4849 - XAF1 and ZNF313 complex stimulates ER stress-induced apoptosis via direct GRP78 inhibition.
Presenter: Sungchan Jang
Session: Poster Display session 1
Resources:
Abstract
4801 - XAF1 assembles a destructive complex to induce BRCA1-mediated apoptosis via suppressing ERa and switching estrogen function
Presenter: Seung-hun Jang
Session: Poster Display session 1
Resources:
Abstract
3416 - Cancer associated fibroblasts promote cancer progression via Wnt2 secretion in colorectal cancer
Presenter: Hideaki Karasawa
Session: Poster Display session 1
Resources:
Abstract
4273 - Paired-related homeobox 1 overexpression promotes invasion and metastasis and is a prognostic factor for worse disease-free survival in patients with lung cancer
Presenter: Jung-jyh Hung
Session: Poster Display session 1
Resources:
Abstract
4241 - LncRNA-GC1 contributes to gastric cancer chemo-resistance through inhibition of miR-551b-3p and the overexpression of dysbindin
Presenter: Xin Guo
Session: Poster Display session 1
Resources:
Abstract
5388 - GLPG 1790, a new selective EPHA2 inhibitor, is active in colorectal cancer cell lines belonging to the CMS4/mesenchymal-like subtype
Presenter: Pietro Paolo Vitiello
Session: Poster Display session 1
Resources:
Abstract
5208 - Characterisation of growth hormone signal transduction in primary melanoma cell lines
Presenter: Karla Sousa
Session: Poster Display session 1
Resources:
Abstract
3156 - LAPTM5 protein can regulate TGF-β mediated MAPK and Smad signaling pathways in ovarian cancer cell
Presenter: Yan Gao
Session: Poster Display session 1
Resources:
Abstract