Abstract CT240: Molecular screening for cancer treatment optimization (MOSCATO 01): a prospective molecular triage trial; Interim analysis of 420 patients

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 analy