Abstract 559P
Background
ES SCLC is an aggressive disease and more effective treatment is needed. CC-90011, a potent, selective, and reversible oral inhibitor of lysine-specific demethylase 1A, had antitumor activity in vitro and in patient (pt)-derived xenografts. CC-90011 is well tolerated and active in pts with advanced solid tumors (Hollebecque A, et al. Ann Oncol. 2019;30 Suppl 1:i4). This study is evaluating CC-90011 + EP for ES SCLC.
Methods
CC-90011-SCLC-001 (NCT03850067) is a phase Ib, first-in-human study of CC-90011 + EP in first-line ES SCLC pts. Pts with central nervous system metastases are excluded. In a chemotherapy phase, pts receive EP plus escalating doses of CC-90011 (20, 40, or 60 mg) on days 1 and 8 of a 21-day cycle for 4-6 cycles. Prophylaxis with granulocyte growth factors is recommended in the chemotherapy phase. Responders to the combination enter a maintenance phase and receive single-agent CC-90011 60 mg once weekly in a 28-day cycle. Primary end points are safety, tolerability, and recommended phase II dose (RP2D) of CC-90011 + EP. Secondary end points are preliminary efficacy, overall survival, and pharmacokinetics (PK).
Results
As of 31 Jan 2020, 13 pts were enrolled and treated with CC-90011 at 20 mg (n=8), 40 mg (n=4), and 60 mg (n=1) + EP. Median age was 66 y. Four pts discontinued (3 from toxicity, 1 from disease progression); 9 pts entered the maintenance phase. One pt experienced dose-limiting toxicity (DLT) of grade 3 neutropenia at CC-90011 20 mg; no DLTs occurred at CC-90011 40 mg. The most frequent grade 3/4 treatment-emergent adverse events (TEAEs) were neutropenia (77%), thrombocytopenia (38%), and anemia (15%) in the chemotherapy phase and thrombocytopenia (44%) in the maintenance phase. In the chemotherapy phase, 2 pts had serious TEAEs, 1 related to CC-90011. No study-drug–related deaths occurred. Of the 13 pts, 11 were efficacy-evaluable and achieved partial response; 2 pts discontinued early due to TEAEs. PK profile of the combination was consistent with monotherapy administration.
Conclusions
Results show CC-90011 + EP is tolerable in first-line ES SCLC. The study is ongoing to establish the RP2D and further evaluate CC-90011/EP.
Clinical trial identification
Study ID: CC-90011-SCLC-001 NCT03850067; 2018-002799-42 (EudraCT Number).
Editorial acknowledgement
Hannah H. Chang, PhD BioConnections, LLC.
Legal entity responsible for the study
Celgene Corporation.
Funding
Celgene Corporation.
Disclosure
L. Paz-Ares: Leadership role: ALTUM Sequencing; Leadership role: Genómica; Honoraria (self): Adacap; Honoraria (self): Amgen; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Blueprint Medicines; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Bristol Myers Squibb; Honoraria (self): Celgene, A Bristol Myers Squibb Company; Honoraria (self): Eli Lilly; Honoraria (self): Incyte; Honoraria (self): Merck; Honoraria (self), Research grant/Funding (self): Merck Sharp and Dohme; Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self): Pharmamar; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Servier; Honoraria (self): Sysmex; Honoraria (self): Takeda; Honoraria (self): Ipsen; Research grant/Funding (self): Dohme. O. Juan-Vidal: Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Takeda; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: MSD. E. Carcereny: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Takeda; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: MSD. L. Greillier: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb; Honoraria (self), Travel/Accommodation/Expenses: Boehringer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Celgene, A Bristol-Myers Squibb Company; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Sanofi. A. Navarro: Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Oryzon Genomics. J. Bennouna: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Servier; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Bayer. A. Santoro: Advisory/Consultancy, Speaker Bureau/Expert testimony: Arqule; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Servier; Advisory/Consultancy, Speaker Bureau/Expert testimony: Gilead; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy: Bayer; Advisory/Consultancy: MSD; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Celgene, A Bristol Myers Squibb Company; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Sandoz. R. Berardi: Advisory/Consultancy: MSD; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Otsuka; Advisory/Consultancy: Lilly. B. Besse: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BeiGene; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): Bristol Myers Squibb; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Celgene, A Bristol-Myers Squibb Company; Research grant/Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): ISPEN; Research grant/Funding (institution): Inivata; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Onxeo; Research grant/Funding (institution): OSE Immunotherapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pharma Mar; Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Tiziana Pharma; Research grant/Funding (institution): Tolero Pharmaceuticals. J. Parra-Palau: Honoraria (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company; Honoraria (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. T. Sánchez-Pérez: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. I. Aronchik: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. E. Filvaroff: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Bristol-Myers Squibb; Shareholder/Stockholder/Stock options: Amgen; Shareholder/Stockholder/Stock options: Gilead; Shareholder/Stockholder/Stock options: Genentech/Roche. M. Lamba: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer; Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, a Bristol-Myers Squibb Company; Research grant/Funding (self), Shareholder/Stockholder/Stock options: Bristol-Myers Squibb. Z. Nikolova: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, a Bristol-Myers Squibb Company. S. Ponce: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Takeda. All other authors have declared no conflicts of interest.