Abstract 8MO
Background
CC-90010, a potent oral BETi, was well-tolerated with promising activity in pts with advanced malignancies. We present longer follow-up results of parts A (A) and B (B) from CC-90010-ST-001 and, for the first time, results from part C (C) describing food effect on CC-90010 pharmacokinetics (PK).
Methods
CC-90010-ST-001 is a phase I dose-escalation (A) and -expansion (B) study of CC-90010 in pts with aSTs and R/R DLBCL also evaluating high-calorie/-fat meal effects on CC-90010 PK in pts with aSTs (C); 11 dose levels (DLs) and 4 schedules (2 weekly [2 d on/5 d off; 3 d on/4 d off], 1 biweekly [3 d on/11 d off] and 1 monthly [4 d on/24 d off]) were tested. Primary objectives were safety, tolerability, maximum tolerated dose and recommended phase II dose (RP2D). Secondary and exploratory objectives were antitumor activity, PK, pharmacodynamics and food effect.
Results
As of 3 Nov 2020, 133 pts were enrolled. In A and B, 67 and 2 pts had aSTs; 2 and 21 pts had R/R DLBCL. In C, 41 pts had aSTs. In A, 6 pts (11%) had dose-limiting toxicities across dosing schedules. The most common grade 3/4 treatment-related adverse event (TRAE) was thrombocytopenia (A, 16%; B, 76%; C, 10%); 8 pts (12%) in A, 6 (29%) in B, and 2 (5%) in C had serious TRAEs. In A, 1 pt (progressing grade 2 astrocytoma) had a complete response (CR) before progression (19 cycles); 1 pt (endometrial carcinoma) had a partial response (PR; 8 cycles). In B, 2 pts with R/R DLBCL responded (CR, PR). In C, 2 pts (parotid basal cell adenocarcinoma, nasopharyngeal cancer) had durable PRs, and 23 had stable disease (≥4 mo in 9 pts); 1 pt (relapsing glioblastoma) had a minor response. Plasma exposures rose dose-proportionally across DLs. CC-90010 terminal half-life was ∼60 h and PK was similar under fasted vs fed conditions in C. CC-90010 ≥25 mg caused ≥50% decrease in CCR1 mRNA (BETi blood biomarker) 4 h after last dose. CCR1 modulation was similar in A and B after first and last dose at the RP2D.
Conclusions
Overall, CC-90010 was very well tolerated with promising antitumor activity and PK not impacted by food intake, supporting exploration in combination therapy.
Clinical trial identification
NCT03220347; EUDRACT 2015-004371-79.
Editorial acknowledgement
Writing and editorial assistance were provided by Brittany L. Phillips, PhD, of Bio Connections LLC, funded by Bristol Myers Squibb Company.
Legal entity responsible for the study
Celgene, a Bristol-Myers Squibb Company.
Funding
Celgene, a Bristol-Myers Squibb Company.
Disclosure
V. Moreno: Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pieris; Advisory/Consultancy: Janssen. M. Vieito Villar: Advisory/Consultancy: Debio; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: TFS; Travel/Accommodation/Expenses: Merck-Serono. J.M. Sepulveda Sanchez: Speaker Bureau/Expert testimony: Astellas; Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: AbbVie; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Celgene, a Bristol-Myers Squibb Company; Advisory/Consultancy: GW Pharma. O. Saavedra: Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Kyowakirin. C. Carlo Stella: Honoraria (self), Speaker Bureau/Expert testimony: MDS; Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self): BMS; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): ADCT; Advisory/Consultancy: Sanofi; Research grant/Funding (institution): Novartis; Travel/Accommodation/Expenses: Takeda; Honoraria (self), Travel/Accommodation/Expenses: Janssen. J-M. Michot: Honoraria (self): Celgene; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): AstraZeneca; Honoraria (self): Janssen. A. Italiano: Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy: Springworks; Advisory/Consultancy: Epizyme; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Merck; Research grant/Funding (self): MSD; Research grant/Funding (self): PharmaMar. M. Magagnoli: Honoraria (self): Sanofi; Honoraria (self): AstraZeneca. C. Carpio: Advisory/Consultancy: Regeneron; Advisory/Consultancy, Travel/Accommodation/Expenses: Takeda; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Gilead; Travel/Accommodation/Expenses: Sandoz; Travel/Accommodation/Expenses: Celgene. R. Sarmiento: Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, a Bristol-Myers Squibb Company. B. Amoroso: Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene. 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. B. Hanna: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: BMS. A. Pinto: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Celgene; Honoraria (self): Servier; Honoraria (self): BMS; Honoraria (self): MSD; Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: Takeda. Z. Nikolova: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Celgene, a Bristol-Myers Squibb Company. I. Braña: Research grant/Funding (self): Celgene, a Bristol-Myers Squibb Company. All other authors have declared no conflicts of interest.