Phase I/II study of weekly PM00104 (Zalypsis® ) in patients with relapsed/refractory multiple myeloma
Ocio EM(1), Oriol A(2), Bladé J(3), Teruel AI(4), Martín J(5), de la Rubia J(6), Gutiérrez NC(7), Rodríguez Díaz-Pavón J(8), Martínez González S(8), Coronado C(8), Fernández-García EM(8), Siguero Gómez M(8), Fernández-Teruel C(8), San Miguel J(9).
(1) Hospital Universitario de Salamanca, IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain.
(2) Hospital Universitario Germans Trias I Pujol, Badalona, Spain.
(3) Hospital Clínico de Barcelona, Institut d'Investigacions Biomediques Auguust Pi I Sunyer, Barcelona, Spain.
(4) Hospital Clínico Universitario de Valencia, Valencia, Spain.
(5) Hospital Universitario Virgen del Rocío, Sevilla, Spain.
(6) Hospital Dr. Peset and Universidad Católica San Vicente Mártir, Valencia, Spain.
(7) Hospital Universitario de Salamanca, IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain.
(8) PharmaMar, Clinical R&D, Colmenar Viejo, Madrid, Spain.
(9) Clínica Universidad de Navarra, Centro de Investigaciones Médicas Aplicadas (CIMA), IDISNA, Pamplona, Spain.
Despite improvements in the prognosis of multiple myeloma (MM) associated with the recent introduction of immunomodulatory drugs (IMIDs), such as thalidomide or lenalidomide, and proteasome inhibitors (PIs), such as bortezomib (Richardson et al, 2003; Dimopoulos et al, 2007), MM remains incurable and virtually all patients relapse. Moreover, patients with relapsed MM refractory to lenalidomide and bortezomib have a dismal prognosis (Kumar et al, 2012) and drugs with different mechanisms of action are currently under investigation (Ocio et al, 2014) for these patients.
PM00104 (Zalypsis®) gives rise to double-strand DNA breaks, increases the G0–G1 phase and induces apoptosis (Ocio et al, 2009) in MM cells. It is effective on cell lines resistant to conventional anti-myeloma treatments and it has shown synergy with several anti-myeloma drugs (Ocio et al, 2009, 2010). A previous phase I trial of PM00104 administered as a 1-h intravenous (i.v.) infusion on Days 1, 8 and 15, every 4 weeks established 2·0 mg/m2 as the recommended dose (RD) in patients with solid tumours (Massard et al, 2013).
The evaluation of this schedule, as well as the optimization of the dose of PM00104 in relapsed/refractory MM, was the main objective of the current trial.
CITATION Br J Haematol. 2015 Jun 2. doi: 10.1111/bjh.13515.