381P - A phase I, open-label, study of GSK2879552, a lysine-specific demethylase 1 (LSD1) inhibitor, in patients with relapsed/refractory small cell lung...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Clinical research
Basic Scientific Principles
Presenter Victor Moreno
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors V. Moreno1, T.M. Bauer2, J. Infante3, R. Govindan4, B. Besse5, E. Bertino6, A. Martinez Marti7, T. Piontek8, A. Dhar9
  • 1Medical Oncology, START Madrid-FJD, Fundación Jiménez Díaz Hospital, 28040 - Madrid/ES
  • 2Drug Development Unit, Sarah Cannon Research Institute/Tennessee Oncology, Nashville/US
  • 3Other, Sarah Cannon Research Institute, Nashville/US
  • 4Medical Oncology, Washington University School of Medicine, 63110 - St. Louis/US
  • 5Departement Of Medicine, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 6Department Of Internal Medicine, Division Of Medical Oncology, Ohio State Univ Medical Center, Columbus/US
  • 7Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 8Rd Projects Clinical Platforms & Sciences, GlaxoSmithKline, Collegeville/US
  • 9Onocolgy R&d, GlaxoSmithKline, Collegeville/US

Abstract

Background

SCLC is initially responsive to chemotherapy; however, patients ultimately relapse. Response to second-line therapy is poor with an overall survival of

Methods

This is a Phase I, open-label, first-time-in-human, 2-part study. Part 1 is a dose escalation phase in patients (≥18 years) with relapsed/refractory SCLC (after ≥1 platinum containing therapy) to determine the safety, tolerability and recommended Phase 2 dose (RP2D) of GSK2879552. Inclusion criteria include: ECOG PS of 0/1; histologically/cytologically confirmed diagnosis of SCLC. One patient will receive a starting dose of 0.25mg of GSK2879552 (orally) once-daily for 28 days, followed by a safety and pharmacokinetic data review, after which dose escalation will begin until an RP2D is determined. In Part 2, the clinical activity (disease control rate at Week 16 based on RECIST 1.1) and safety of GSK2879552 will be evaluated at the RP2D in an expansion cohort of ≤30 patients with recurrent SCLC. Patients must have received ≤2 prior chemotherapy regimens, including ≥1 containing platinum, and have measurable disease.

Results

Additional study objectives include: analysis of pharmacokinetics of GSK2879552 after single and repeat dosing, evaluation of the relationship between GSK2879552 exposure and safety/efficacy/pharmacodynamic parameters, duration of response, progression-free survival, and objective response rate.

Conclusions

Recruitment is ongoing across six centers (USA, France and Spain); 47 patients will be enrolled in Part 1 and 30 in Part 2. Study funded by GSK.

Clinical trial identification

NCT02034123

Legal entity responsible for the study

GSK

Funding

GSK

Disclosure

J. Infante: Research funding from GSK. R. Govindan: Dr. Govindan personal fees from Boehringer Ingelheim, GlaxoSmithKline, Clegene, Merck, Bayer, Genentech, Clovis Oncology, Helsinn Healthcare and Pacritinib outside the submitted work. A. Dhar: Full-time/part-time employee of GSK Stock shareholder (self managed) of GSK. All other authors have declared no conflicts of interest.