LY3039478 (LY) is an orally bioavailable selective Notch inhibitor (Notch 1-4). Here we report on safety, pharmacodynamics (PD), and anti-tumour activity of LY in patients (pts) with STS/GIST.
This ongoing, multi-part, phase 1 trial enrolled pts with refractory advanced or metastatic STS and GIST, measurable disease, ECOG score ≤1, and baseline tumour tissue. Eligible pts received LY 50 mg three times per week (TIW), for a 28-day cycle until disease progression. Safety assessments were based on CTCAE V4.0. Tumour responses were assessed using RECIST 1.1 and Choi criteria. Primary objectives are to confirm the recommended phase 2 dose of LY and document antitumour activity. Secondary objectives are safety and toxicity, PD, progression-free survival (PFS) and overall survival (OS).
63 pts have been enrolled and received LY (24 males, 39 females; median age 58, range 31-76). 26 pts had leiomyosarcoma (LMS), 9 liposarcoma, 7 pleomorphic sarcoma, 6 angiosarcomas, 5 rhabdomyosarcoma and 10 GIST. 18 out of 39 (46%) pts with evaluable tumour samples were positive for Notch 1 ICD. 5% and 13% were positive for Notch 2 ICD, and Notch 3 respectively. Per RECIST, 2 out of 53 pts with STS had unconfirmed PR, and 20 SD. In GIST group, 4 pts had SD. Using Choi Criteria, 5 pts in STS had unconfirmed PR. Overall median PFS was 1.74 months (95% CI: 1.68-2.60) and consistent across histology groups (median PFS=2.23, 1.91 and 1.68 months for LMS, GIST and other STS, respectively). PFS rate at 3 months was 42% in LMS, 39% in GIST and 15% in other STS respectively. OS and biomarker/histologic analyses of pre and post treatment biopsies will be presented at the meeting. Most frequent related adverse events (all grades) occurring in ≥ 20% of pts included diarrhoea 44 (70%), vomiting 24 (38%), nausea 21 (33%), decreased appetite 17 (27%), fatigue 17 (27%) asthenia 16 (25%), hypophosphataemia 14 (22%).
LY suggested activity in pts with STS and GIST and had a manageable safety profile.
Clinical trial identification
Trial protocol number: Protocol I6F-MC-JJCA(e) Clinicaltrials.gov ID: NCT01695005 Release date: 08-July-2016
Legal entity responsible for the study
Eli Lilly and Company
Eli Lilly and Company
O. Mir: Speaker Bureau: Eli Lilly, Roche. Consulting/advisory board member: Amgen, Astra-Zeneca, Bayer, BMS, Eli Lilly, Netcancer, Novartis, Pfizer, Roche, Servier. A. Azaro: Member of Orion SMB. J.R. Merchan: Consulting/Advisory role: Exelixis. Research Funding: Rexahn, Eli Lilly, Novartis, Tocagen, Agensys, Tracon. R. Chugh: Stakeholder: Portala. Advisory board member: EMD Serano, Epizyme. Research funding: Eli Lilly, Novartis, Morphotek, Mabvax, Epizyme. J.C. Trent: Member of advisory board: Eli Lilly, Janssen, Eisai, Novartis, Eayer, Blueprint, Deciphera. J. Rodon: Advisor/board member: Eli Lilly, Novartis, and Servier. U. Ohnmacht: Stakeholder: Eli Lilly and Company. A. Le Cesne: Received honoraria: PharmaMar, Lilly, Amgen, Novartis, and Pfizer. J-C. Soria: Advisory board member: Eli Lilly and Company. C. Massard: Advisory board member, speaker, investigator: Amgen, Astellas, Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Janssen, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, Orion. All other authors have declared no conflicts of interest.