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
Author(s):

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 .

Abstract:
Background:

 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). 

Methods: 

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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Genomica SAU . ASCO18 . Non-Small Cell Lung Cancer (NSCLC ) .

A Comparative Study of ALK and ROS Genes Rearrangements Among IHC/FISH/CLART in NSCLC.

2018 ASCO Annual Meeting .

Author(s): Maria Cortes-Sempere, Maria Jesus Sanz, Nuria Manjon, Marta Sanchez-Muñoz, Rosa Somoza, Yolanda Ruano, Irene Sansano, Javier Hernandez-Losa, Jose Luis Rodriguez-Peralto, Maria Luisa Villahermosa; GENOMICA SAU, Madrid, Spain; Genomica SAU, Madrid, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain; 12 de Octubre Universitary Hospital, Madrid, Spain; Pathological Anatomy Service, Hospital Doce de Octubre, Madrid, Spain.

Abstract Disclosures

Abstract:

Background: With the launching of the new GENOMICA’s kit for the detection of ALK and ROS1 genes rearrangements in non-small cell lung cancer (NSCLC), a comparative study with the current two routine diagnosis techniques, immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) was performed. CLART CMA ALK-ROS.1 detects the main chromosomal translocations of ALK gene with EML.4 and ROS1 gene with SDC4, CD74 and SLC34A2 in patients with lung cancer. Starting material is extracted RNA from lung biopsies in the form of formalin-fixed paraffin-embedded tumor tissue (FFPE). Detection is based on our CLART® technology: End-point Multiplex PCR amplification, followed by visualization in low-density microarray. The objective of this study is to determine the diagnostic validity of the GENOMICA CLART system as a routine technique in the detection of these rearrangements in clinical practice.

Methods: Two Spanish hospitals participated in this clinical study: Hospital Universitario 12 de Octubre from Madrid and Hospital Vall d’Hebron from Barcelona. 86 FFPE tissue samples from NSCLC were obtained by surgery, bronchoscopy or biopsy-puncture. They were assessed with IHC or/and FISH and with CLART system in parallel. The discrepancies were analysed by NGS with the Oncomine™ Focus Assay panel from Thermo Fisher Scientific.

Results: 6 out of 86 samples were positive with the routine techniques, 1 positive for ROS1 and 5 for ALK rearrangements. Out of these 6 samples, 3 were positive and 3 were negative with CLART system. The 3 discrepancies were analysed by NGS and 1 resulted positive for a ROS1 variant that GENOMICA kit does not detect and the other 2 discrepancies were WT.

Conclusions: Comparing the results obtained from CLART system and IHC/FISH we have a 96.5% of concordance, but after the discrepancies analysis by NGS we could observe that the results of the routine techniques had 3 false negatives and that CLART system have a 100% of sensitivity and specificity. CLARTCMA ALK-ROS.1 may provide an effective and accurate alternative to FISH/IHC testing for the detection of known EML4-ALK and ROS1 rearrangements in clinical diagnostic settings, being a method easy to perform and to be integrated into clinical routine.