1420TiP - ANNOUNCE 2: An open-label phase 1b, and a randomized, double-blind phase 2 study of olaratumab with gemcitabine plus docetaxel in the treatment of...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Cytotoxic agents
Soft Tissue Sarcomas
Therapy
Biological therapy
Presenter Andres Redondo
Citation Annals of Oncology (2016) 27 (6): 483-492. 10.1093/annonc/mdw388
Authors A. Redondo1, C. Valverde Morales2, N. Hindi3, J.A. Lopez-Martin4, G. Honigschmidt5, Y. Zeng5, J. Chen5, D.F. Tai5, G. Mo5, R. Ilaria Jr5, N.S. Pillay5, N. Drove5, M. Jamarik6
  • 1Oncology, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 2Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 3Oncology, Hospital Universitario Virgen del Rocio, Sevilla/ES
  • 4Oncology, University Hospital 12 De Octubre, Madrid/ES
  • 5Oncology, Eli Lilly and Company, Indianapolis/US
  • 6Oncology, Eli Lilly Slovakia, Bratislava/SK

Abstract

Background

While doxorubicin has been the mainstay of treatment for decades, in more recent years gemcitabine plus docetaxel has emerged as an effective treatment in metastatic STS. The platelet-derived growth factor receptor alpha (PDGFR α) antibody olaratumab in combination with doxorubicin demonstrated a significant improvement of overall survival over doxorubicin alone in patients with advanced STS in a randomized phase 2 study (NCT01185964). Since some patients may not be appropriate candidates for doxorubicin-based chemotherapy, or have received prior anthracycline treatment, exploring the efficacy and safety of olaratumab with gemcitabine plus docetaxel is of considerable interest.

Trial design

ANNOUNCE 2 (NCT02659020) is a multicentre Phase 1b/2 study of olaratumab in combination with gemcitabine and docetaxel in patients with advanced or metastatic STS (≥16 years; ECOG performance status ≤1; naïve to therapy with study drugs; not amenable to curative treatment with surgery or radiotherapy; ≤2 prior lines of systemic therapy for advanced or metastatic disease). The Phase 1b part of the study consists of an open-label, single-arm, dose-escalation assessment of the safety and tolerability of olaratumab administered at 15 mg/kg (Days 1 and 8) or 20 mg/kg (Days 1 and 8) with gemcitabine (900 mg/m2 [fixed dose rate: 10 mg/m2/minute] Days 1 and 8) and docetaxel (75 mg/m2 Day 8) in a 21-day cycle. The primary objective is to determine a dose of olaratumab that may be safely administered in combination with gemcitabine and docetaxel in patients with advanced or metastatic STS. Secondary objectives are to evaluate the safety and toxicity profile, pharmacokinetics, and immunogenicity of olaratumab in combination with gemcitabine and docetaxel; and to document any antitumor activity. After the optimal dose of olaratumab in combination with gemcitabine and docetaxel has been determined, the Phase 2, randomized, double-blind, placebo-controlled part of the study will open to enrolment (in approximately December 2016). The study began in March 2016; planned enrollment for the 1b phase is approximately 30 patients.

Clinical trial identification

NCT02659020

Legal entity responsible for the study

Eli Lilly and Company

Funding

Eli Lilly and Company

Disclosure

C. Valverde Morales: Honoraria from Eli Lilly and Company as advisor for educational activities. J.A. Lopez-Martin: Eli Lilly and Company: advisory board, clinical research grants. MSD, BMS, Novartis, GSK, Roche: advisory board, clinical research grants. PharmaMar: former employee, stocks. G. Honigschmidt, Y. Zeng, J. Chen, D.F. Tai, G. Mo, R. Ilaria Jr, N.S. Pillay, N. Drove, M. Jamarik: Employee of Eli Lilly and Company. All other authors have declared no conflicts of interest.