Background: The widespread use of high-throughput molecular techniques has allowed the identification of recurrent and actionable molecular traits across various tumor types. Translating these approaches to bedside may guide the decision-making for cancer patients candidates to early clinical trials.

Methods: Patients with advanced solid tumors, refered to our early drug development department (DITEP), were prospectively enrolled in a prospective molecular screening program at Gustave Roussy (France). CT-Scan or ultrasound-guided biopsies were performed in metastatic or primary tumor sites to carry out a comprehensive molecular characterization. DNA was extracted from fresh tumor samples and analyzed by comparative genomic hybridization (CGH) (≥ 30% tumor cells required) and by Next Generation Sequencing (NGS) for up to 74 target genes (≥ 10% tumor cells required). A weekly molecular tumor board reviewed all the profiles to identify actionable traits for which the most relevant targeted therapy may be available through early clinical trials or marketed drugs. Treatment efficacy was evaluated by RECIST 1.1 criteria.

Results: From November 2011 to December 2013, 420 heavily pretreated patients were included in the MOSCATO 01 trial. Out of them, a tumor biopsy could be performed in 368 patients (87%). CGH and NGS profiles were assessed in 284 (77%) and 315 (85%) of biopsied patients, respectively, with 283 patients (76% of biopsied patients) being profiled for both CGH and NGS. The median time for delivering results of 20 days. Actionable molecular aberrations were found in 161 patients (44%). Among them, 81 patients (50%) were matched to a targeted therapy and enrolled in ongoing phase I clinical trials. The most relevant genomic aberrations of interest were FGFR or FGF ligand amplification (n=24), PTEN/PI3K/AKT pathway activation (n=22), HER2 amplification (n=11), KRAS/NRAS/HRAS mutation (n=5), BRAF mutation (n=4), cyclin dependent kinase amplification or deletion (n=8), EGFR amplification or mutation (n=7), MET amplification (n=3), androgen receptor amplification (n=2), ALK translocation (n=2), and KIT amplification, MDM2 amplification, IGF1R amplification, and ROS1 rearrangement (all n=1). Out of the 81 patients profiled and treated according to the genomic profiles, we observed at the first tumor evaluation: 1 (1%) complete response (CR), 9 (11%) partial responses (PR), 52 (64%) stable disease (SD) and 14 (17%) progressive disease (PD). Whole exome analyses on selected patients are ongoing (currently n=24) and will be presented at the meeting.

Conclusions: High throughput genomic analysis is feasible in daily practice and allows biological-orientation of patients in early clinical trials. The enrichment of phase I trials with patients harboring specific molecular traits leads to promising antitumor activity and is likely to exert a major influence on early drug development.

Citation Format: Charles Ferté, Christophe Massard, Ecaterina Ileana, Antoine Hollebecque, Ludovic Lacroix, Samy Ammari, Maud Ngo-Camus, Rastislav Bahleda, Anas Gazzah, Andrea Varga, Sophie Postel-Vinay, Yohann Loriot, Nathalie Auger, Valerie Koubi-Pick, Bastien Job, Thierry De Baere, Frederic Deschamps, Philippe Vielh, Vladimir Lazar, Marie-Cécile Le Deley, Catherine Richon, vincent ribrag, eric deutsch, eric angevin, gilles vassal, Alexander Eggermont, Fabrice André, Jean-Charles Soria. Molecular screening for cancer treatment optimization (MOSCATO 01): a prospective molecular triage trial; Interim analysis of 420 patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT240. doi:10.1158/1538-7445.AM2014-CT240