03 junio 2018

Zepsyre ( Atlantis ) ASCO18 - 3 de Junio . Lurbinectedin combinado con Doxorubicin . Fase III para el Tratamiento de Pacientes con Cáncer de Pulmón de Celulas Pequeñas ( SMCLC ) .

ATLANTIS : Global, Randomized Phase III Study of Lurbinectedin (L) with Doxorubicin (DOX) vs. CAV or Topotecan (T) in Small-Cell Lung Cancer after Platinum Therapy.

Principal Autor :

 Anna F. Farago, MD , PhD . Massachussetts General Hospital .

Meeting : 2018 ASCO Annual Meetin .
Abstract No : TPS8587

Anna F. Farago, Luis G. Paz-Ares, Tudor-Eliade Ciuleanu, Andrea Fülop, Alejandro Navarro, Laura Bonanno, Jose Antonio Lopez-Vilariño, Rafael Nuñez, Carmen Maria Kahatt, Gabor Kos, Arturo Soto-Matos; Massachusetts General Hospital, Boston, MA; University Hospital 12 de October, Madrid, Spain; Chiricuta Institute of Oncology, Cluj County, Romania; Orszagos Koranyi TBC es Pulmonologiai Intezet 6, Budapest, Hungary; Vall d'Hebron University Hospital, Barcelona, Spain; Istituto Oncologico Veneto IOV IRCCS, Padova, Italy; PharmaMar, Madrid, Spain; Syneos Health, Budapest, Hungary .


 Lurbinectedin (L), a synthetic analog of marine-based tetrahydroisoquinolone, blocks active transcription, produces DNA breaks and apoptosis, and affects the inflammatory microenvironment. L showed promising activity in combination with DOX in a phase I cohort of relapsed small cell lung cancer (SCLC) patients (pts) (overall response rate (ORR) = 67%, n = 21, ASCO 2015, abstract 7509). Most common toxicities were hematologic. Lower dose improved safety and confirmed activity in an expanded cohort (ORR = 37%, n = 27 SCLC pts). 


We present an ongoing multinational (20 countries), multicenter (154 sites), open-label, randomized phase III study of L/DOX vs. control arm (investigator choice of either cyclophosphamide, DOX and vincristine (CAV) or topotecan (T)). 600 pts will be randomized (1:1) and stratified according to ECOG performance status (PS), central nervous system (CNS) involvement, previous treatment with antiPD1/antiPD-L1, chemotherapy-free interval, and investigator´s choice of control arm. Interim safety analysis by an independent data monitoring committee (IDMC) is planned when the first 150 pts are randomized. The most relevant inclusion criteria are: age ≥18 years; confirmed SCLC diagnosis (if primary site unknown, Ki-67 expression > 50%); previous platinum-containing line (additional immunotherapy allowed); ECOG PS 0-2; adequate major organ function (including LVEF > 50%). Main exclusion criteria include chemotherapy-free interval < 30 days; prior treatment with L DOX or T; symptomatic or steroids-requiring CNS involvement. 

The primary objective is to determine a difference in progression-free survival (RECIST v.1.1) by independent review committee. 

Secondary endpoints include overall survival, survival rates at 12/18/24 months, antitumor response, duration of response, quality of life, safety, and pharmacokinetics.

The first patient was randomized in August 2016.

The Pre-Planned interim Safety Analysis was done on MAY 2018 and the IDMC Recommended to Continue the Trial Unmodified.

Trial recruitment is expected to be completed in Q2 2018.

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