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
2728 - MicroRNA expression and DNA methylation profiles do not distinguish between primary and recurrent well-differentiated liposarcoma
Presenter: Melissa Vos
Session: Poster Display session 1
Resources:
Abstract
3197 - Genomic Alterations, Tumor Mutation Burden and Prognosis of Chinese Cardiac Sarcoma Patients
Presenter: Na Zhu
Session: Poster Display session 1
Resources:
Abstract
4214 - Evaluation of a peptide-conjugated alkylator melflufen in osteosarcoma preclinical models
Presenter: Konstantin Byrgazov
Session: Poster Display session 1
Resources:
Abstract
2654 - Expression analysis of NHEJ and HR genes in Ewing sarcomas: indications of DSB repair dysfunction
Presenter: Anastasios Kyriazoglou
Session: Poster Display session 1
Resources:
Abstract
4383 - Epidemiology of Synovial Sarcoma in EU28 countries
Presenter: Nedra Joseph
Session: Poster Display session 1
Resources:
Abstract
1937 - Resection Of High-Grade Large Soft Tissue Sarcoma With Adequate Wide Margin Can Lead To Good Local Control Without Adjuvant Radiotherapy
Presenter: Toshiyuki Kunisada
Session: Poster Display session 1
Resources:
Abstract
3757 - Influence of eribulin on proliferation, migration and invasion properties of leiomyosarcoma cell line models
Presenter: Marta Mendiola
Session: Poster Display session 1
Resources:
Abstract
1040 - EREMISS: Efficacy of regorafenib (REG) as maintenance therapy in non-adipocytic soft tissue sarcomas (STS) having received 1st-line doxorubicin-based chemotherapy (Doxo-CT)
Presenter: Nicolas Penel
Session: Poster Display session 1
Resources:
Abstract
1048 - A Phase 2 biomarker-driven study evaluating the clinical efficacy of an MDM2 inhibitor, milademetan, in patients with intimal sarcoma, a disease with a high unmet need
Presenter: Kan Yonemori
Session: Poster Display session 1
Resources:
Abstract
1511 - A pilot study of oral paclitaxel (ORAXOL) in subjects with cutaneous angiosarcomas (KX-ORAX-010)
Presenter: Herbert Loong
Session: Poster Display session 1
Resources:
Abstract