528O - CC-90011 in patients (Pts) with advanced solid tumours (STs) and relapsed/refractory non-Hodgkin lymphoma (R/R NHL): Updated results of a phase I study

Background

CC-90011 is an oral, potent, selective, reversible inhibitor of lysine-specific demethylase 1A. CC-90011 was well tolerated and had promising antitumor activity in pts with advanced unresectable STs and R/R NHL in the dose-escalation part of the CC-90011-ST-001 study. Here we present updated results from the cohort expansion part of the study.

Methods

Pts in this phase I, dose-escalation (part A) and -expansion (part B), first-in-human study received CC-90011 once/wk (QW) in 28-d cycles. Primary endpoints were safety, maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy.

Results

Sixty-six pts enrolled, 50 in part A (27 with neuroendocrine neoplasms [NENs] and 1 with R/R NHL) and 16 in part B (all with NENs). The RP2D was 60 mg QW. As of 17 Jan 2020, 4 pts (3 with NENs, 1 with R/R NHL) in part A and 2 pts in part B remained on treatment (tx). The primary reason for tx discontinuation was progressive disease (part A, n=38 [76%]; part B, n=12 [75%]). Thrombocytopenia was the most common tx-related adverse event (AE; 47%), and the only serious AE reported in >1 pt in either part of the study; this on-target toxicity was reversible and manageable. AEs led to discontinuation in 3 pts (6%), all in part A. Two pts in part A and 1 in part B died due to underlying disease; there were no deaths due to tx-related AEs. Clinical benefit rate (partial or complete response [CR] or stable disease [SD] ≥4 mo) was 20% (95% CI, 10.0-33.7) in part A and 44% (95% CI, 19.8-70.1) in part B. In part A, the R/R NHL pt achieved a CR (ongoing in cycle 32) and 5 pts with NENs had SD ≥9 cycles, including 2 with SD ≥21 cycles. In part B, 3 pts with NENs had SD ≥9 cycles. Exposure increased proportional to dose. Negligible accumulation of exposure occurred with repeat dosing and systemic exposures at the same dose were similar in parts A and B. Decreased levels of chromogranin A and peripheral blood PD biomarker, MMD, indicated CC-90011 target engagement.

Conclusions

CC-90011 was well tolerated with favorable PK/PD profiles. Promising antitumor activity was observed in pts with NENs and R/R NHL.

Clinical trial identification

Study ID: CC-90011-ST-001 NCT02875223.

Editorial acknowledgement

Tisheeka Graham-Steed, PhD BioConnections, LLC.

Legal entity responsible for the study

Celgene Corporation.

Funding

Celgene Corporation.

Disclosure

A. Hollebecque: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Honoraria (institution): Eisai; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Servier; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Debiopharm; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Medimmune. 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: Astellas; 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. R. Plummer: Advisory/Consultancy: Pierre Faber; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: Octimet; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Karus Therapeutics; Advisory/Consultancy: Biosceptre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol Myers Squibb; Advisory/Consultancy: Cybrexa; Advisory/Consultancy: Ellipses; Advisory/Consultancy: CV6 Therapeutics; Advisory/Consultancy: Astex Therapeutics; Advisory/Consultancy: Sanofi Aventis; Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Speaker Bureau/Expert testimony: Tesaro; Travel/Accommodation/Expenses: MSD. G. Curigliano: 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; Speaker Bureau/Expert testimony: PRIME ; Speaker Bureau/Expert testimony: Accademia Nazionale di Medicina; Speaker Bureau/Expert testimony: MedScape. V. Moreno: Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pieris; Advisory/Consultancy: Janssen. F. de Braud: Advisory/Consultancy: TizianaLife Sciences; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Celgene, A Bristol-Myers Squibb Company; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Servier; Advisory/Consultancy: Pharm Research Associated; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ignyta; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Octimet Oncology; Advisory/Consultancy: Incyte; Advisory/Consultancy: Teofarma; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: EMD Serono; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Tesaro; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Gentili; Speaker Bureau/Expert testimony: Fondazione Menarini; Speaker Bureau/Expert testimony: Menarini; Speaker Bureau/Expert testimony: MSD; 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. P. Martin-Romano: Research grant/Funding (self), Non-remunerated activity/ies: AstraZeneca; Research grant/Funding (self), Non-remunerated activity/ies: Bristol Myers Squibb; Research grant/Funding (self), Non-remunerated activity/ies: Boehringer Ingelheim; Research grant/Funding (self): Janssen Cilag; Research grant/Funding (self), Non-remunerated activity/ies: Merck; Research grant/Funding (self): Novartis; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Roche; Research grant/Funding (self): Sanofi; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: Johnson & Johnson; Non-remunerated activity/ies: Lilly; Non-remunerated activity/ies: Medimmune; Non-remunerated activity/ies: NH TherA. E. Baudin: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ipsen; Speaker Bureau/Expert testimony: AAA; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Hutchinson Pharma. J. Parra-Palau: Honoraria (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, A Bristol-Myers Squibb Company. 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. All other authors have declared no conflicts of interest.