CC-90011, an oral, potent, selective, and reversible inhibitor of lysine-specific demethylase 1A, was well tolerated and showed antitumor activity in the first-in-human CC-90011-ST-001 study of pts with advanced unresectable STs and R/R NHL. Here, we present updated results with longer follow-up.
Pts in this phase I, dose-escalation (part A) and -expansion (part B) study received CC-90011 once/wk (qw) in 28-d cycles (Cs). Primary endpoints were safety, maximum tolerated dose, and recommended phase II dose (RP2D). The key secondary endpoint was preliminary efficacy, and exploratory endpoints included pharmacokinetics and pharmacodynamics (PD).
As of 11 Sept 2020, 67 pts were enrolled, 50 in part A (27 with NENs, 1 with R/R NHL) and 17 in part B (16 with NENs, 1 with R/R NHL). Thrombocytopenia, an on-target toxicity, was the most common treatment-emergent adverse event (AE; 46% in part A, 71% in part B), the only serious AE reported in >2 pts in either part of the study, and successfully managed with dose modification. AEs led to discontinuation in 3 pts, all in part A. There were no deaths due to treatment-related AEs. Longer follow-up confirmed the good tolerability of CC-90011. The clinical benefit rate was 20% (95% CI, 10.0-33.7) in part A and 41% (95% CI, 18.4-67.1) in part B. As of 25 Nov 2020, 2 pts in part A (1 with solitary fibrous tumor [SFT] and 1 with R/R NHL) and 2 pts in part B (both with bronchial NENs) remained on treatment. In part A, the pt with R/R NHL achieved a complete response (CR; ongoing in C39), a pt with SFT achieved a partial response (PR) in C36 (ongoing in C42), and 5 pts with NENs had stable disease (SD)≥9 Cs, including 1 with SD ≥32 Cs. In part B, 3 pts with NENs had SD≥9 Cs, including 2 ongoing in C21 and C27. CC-90011 target engagement was indicated by decreased levels of chromogranin A and MMD in pts’ peripheral blood. PD marker changes at RP2D (60 mg qw) were consistent in part A and part B.
CC-90011 was well tolerated and demonstrated promising antitumor activity, including a durable CR in R/R NHL, a PR in SFT, and prolonged SD in NENs. These data support further investigation of CC-90011 as monotherapy and in combination with other therapies.
NCT02875223; EUDRACT 2015-005243-13.
Writing and editorial assistance were provided by Yaeko Hiyama, PhD, of Bio Connections LLC, funded by Bristol-Myers Squibb Company.
Celgene, a Bristol-Myers Squibb Company.
Celgene, a Bristol-Myers Squibb Company.
A. Hollebecque: Honoraria (self), Honoraria (institution), Shareholder/Stockholder/Stock options: BMS; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Honoraria (self), Honoraria (institution): Eisai; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Servier; Advisory/Consultancy: Gritstone Oncology; Advisory/Consultancy: QED Therapeutic; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Incyte; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy: Debiopharm; Travel/Accommodation/Expenses: Roche. J.S. de Bono: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sierra Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genmab; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: GSK; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Menarini Silicon Biosystems; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Orion; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Taiho; Research grant/Funding (institution): Cellcentric; Research grant/Funding (institution): Celgene a Bristol-Myers Squibb Company; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas; Licensing/Royalties: My institution has commercial interest in abiraterone, PARP inhibition in DNA repair defective cancers and PI3K/AKT pathway inhibitors (no personal income); Leadership role: CI/PI of many industry sponsored clinical trials. R. Plummer: Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony: Tesaro; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Octimet; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Karus Therapeutics; Advisory/Consultancy: Biosceptre; Advisory/Consultancy: Cybrexa; Advisory/Consultancy: Ellipses; Advisory/Consultancy: CV6 Therapeutics; Advisory/Consultancy: Astex Therapeutics; Advisory/Consultancy: Sanofi Aventis; Travel/Accommodation/Expenses: MSD. G. Curigliano: Speaker Bureau/Expert testimony: priME; Speaker Bureau/Expert testimony: Accademia Nazionale di Medicina; Speaker Bureau/Expert testimony: Medscape; Honoraria (self): Ellipsis; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Samsung. V. Moreno: Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pieris; Advisory/Consultancy: Janssen. F. De Braud: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Gentili; Speaker Bureau/Expert testimony: Fondazione Menarini; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ignyta; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Speaker Bureau/Expert testimony: Noema S.r.l.; Speaker Bureau/Expert testimony: ACCMED; Speaker Bureau/Expert testimony: Dephaforum S.r.l.; Speaker Bureau/Expert testimony: Nadirex; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Biotechspert Ltd.; Speaker Bureau/Expert testimony: priME Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Tiziana Life Sciences; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Celgene, a Bristol-Meyers Squibb Company; Advisory/Consultancy: Servier; Advisory/Consultancy: Pharm Research Associated; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Octimet Oncology; Advisory/Consultancy: Incyte; Advisory/Consultancy: Teofarma; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: EMD Serono; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Tesaro. P. Martin-Romano: Research grant/Funding (institution), Non-remunerated activity/ies, Non-financial support (drug supplied): AstraZeneca; Research grant/Funding (institution), Non-remunerated activity/ies, Non-financial support (drug supplied): BMS; Research grant/Funding (institution), Non-remunerated activity/ies, Non-financial support (drug supplied): Boehringer Ingelheim; Research grant/Funding (institution): Janssen Cilag; Research grant/Funding (institution), Non-remunerated activity/ies, Non-financial support (drug supplied): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution), Non-remunerated activity/ies, Non-financial support (drug supplied): Pfizer; Research grant/Funding (institution), Non-remunerated activity/ies, Non-financial support (drug supplied): Roche; Research grant/Funding (institution): Sanofi; Non-remunerated activity/ies, Non-financial support (drug supplied): Bayer; Non-remunerated activity/ies, Non-financial support (drug supplied): Johnson & Johnson; Non-remunerated activity/ies, Non-financial support (drug supplied): Lilly; Non-remunerated activity/ies, Non-financial support (drug supplied): MedImmune; Non-remunerated activity/ies, Non-financial support (drug supplied): NH TherAGuiX. E. Baudin: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ipsen; Speaker Bureau/Expert testimony, Non-remunerated activity/ies, Other Relationship: AAA; Non-remunerated activity/ies, Other Relationship: Pfizer; Speaker Bureau/Expert testimony: Hutchinson Pharma. J. Parra-Palau: Honoraria (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene/BMS. T. Sánchez-Pérez: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene/BMS. I. Aronchik: Shareholder/Stockholder/Stock options, Full/Part-time employment: BMS. E. Filvaroff: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: BMS; 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 (now part of Bristol-Myers Squibb); Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. Z. Nikolova: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. All other authors have declared no conflicts of interest.