0000000000082755
AUTHOR
Antoine Hollebecque
showing 6 related works from this author
A phase IB, multicenter, open-label study to assess the safety, tolerability, and efficacy of the pleiotropic pathway modifier CC122 administered ora…
2017
379 Background: CC122 is a novel cereblon-modulating agent with multiple biologic activities including potent immunomodulatory and antiangiogenic effects. CC-122 binding to cereblon promotes ubiquitination and subsequent degradation of lymphoid transcription factors Ikaros and Aiolos resulting in activation of T cells. Methods: Following establishment of oral CC122 3 mg daily (QD) as the MTD in phase 1a (Blood 122:2905 2013), an expansion cohort of advanced Hepatocellular Carcinoma (HCC) subjects was enrolled. All subjects had progressed on or were intolerant to sorafenib. Efficacy was assessed per RECIST 1.1 criteria. Results: As of Jan. 13, 2016, 25 advanced HCC subjects were enrolled. T…
Phase I multicenter, open-label study to establish the maximum tolerated dose (MTD) of trifluridine/tipiracil (TAS-102) and oxaliplatin combination i…
2018
816 Background: Preclinical evidence suggests improved efficacy when combining trifluridine/tipiracil with oxaliplatin compared to each monotherapy (Nukatsuka, 2015). The primary objective was to determine the MTD and the safety profile of the doublet among mCRC pts who have progressed after at least one prior line of treatment. Methods: Using a 3+3 design, eligible pts received escalating trifluridine/tipiracil doses from 25, 30 to 35 mg/m² bid, days 1–5 q14, together with a fixed dose of oxaliplatin 85 mg/m² (day 1). An intermediate cohort with a lower dose of oxaliplatin (65 mg/m²) plus 35 mg/m² of trifluridine/tipiracil was also tested. Results: Fifteen of 17 enrolled pts were evaluabl…
Phase I dose-escalation of trifluridine/tipiracil in combination with oxaliplatin in patients with metastatic colorectal cancer
2019
Abstract Background and objectives Pre-clinical data have shown that combining trifluridine/tipiracil with oxaliplatin enhances anti-tumour activity compared with either monotherapy. A phase I dose-escalation study was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD) for phase II and pharmacokinetic profile of this combination in patients with metastatic colorectal cancer (mCRC) who had progressed after at least 1 prior line of treatment. Methods Using a 3 + 3 design, patients received escalating trifluridine/tipiracil doses from 25, then 30 and to 35 mg/m2 twice daily, days 1–5, q14 days, together with a fixed dose of 85 mg/m2 of oxaliplatin day 1, q14 days. A…
PI3K/AKT Activation and Response in Phase IB: AKT Inhibitor GDC-0068 with Docetaxel (D) Or MFOLFOX6 (F) in Refractory Solid Tumors
2013
R. Meng1, L. R. Molife2, L. de Mattos-Arruda3, A. Hollebecque4, S. J. Isakoff5, D. Roda6, Y. Yan1, A. Cervantes6, J. C. Soria4, J. Mateo2, G. Argiles3, J. C. Bendell7 Genentech, South San Francisco, CA, USA, Institute of Cancer Research/ Royal Marsden Hospital, Sutton, United Kingdom, Vall d’Hebron University Hospital, Barcelona, Spain, Institut Gustave Roussy, Villejuif, France, Massachusetts General Hospital, Boston, MA, USA, Institute of Health Research INCLIVA, University of Valenica, Valencia, Spain, Sarah Cannon Research Institute, Nashville, TN, USA
A phase Ib study of the Akt inhibitor GDC-0068 with docetaxel (D) or mFOLFOX-6 (F) in patients (pts) with advanced solid tumors.
2012
3021 Background: Activation of the Akt pathway is observed in multiple tumors and may contribute to chemoresistance. GDC-0068 is an ATP-competitive small molecule inhibitor of all three isoforms of Akt; in a phase Ia study, it was well tolerated with maximum tolerated dose (MTD) of 600 mg daily (21 days on/7days off) and pharmacodynamic down-regulation of Akt signaling in tumors at doses ≥100 mg. In vitro, GDC-0068 shows synergism with cytotoxic agents. This phase Ib study defines the dose limiting toxicities (DLT), MTD, safety and pharmacokinetics (PK) of GDC0068 in combination with D and F. Methods: Using a 3+3 designeligible patients (pt) with advanced/metastatic solid tumors were treat…
A phase I dose-escalation of trifluridine/tipiracil in combination with oxaliplatin in metastatic colorectal cancer.
2017
TPS3626 Background: Trifluridine/tipiracil, also known as TAS‐102, is a combination of an antineoplastic thymidine‐based nucleoside analogue (trifluridine) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride). The antitumor activity of combined trifluridine/tipiracil and oxaliplatin has been studied in gastrointestinal tumor xenografts, including a 5‐FU resistant subline, using a nude mouse model. This study demonstrated increased antitumor activity for the combination compared to trifluridine/tipiracil or oxaliplatin alone (p < 0.001) (Nukatsuka et al., Anticancer Res 2015). These data support the rationale for clinical use of the combination. We describe a phase 1, intern…