5049 - CLEPSIDRA trial: a pilot, biomarker-guided study to assess safety, tolerability, dose finding and efficacy of iadademstat in combination with platinum-etoposide in patients with relapsed, extensive-stage small cell lung cancer

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.