Abstract CT004: European pediatric precision medicine program in recurrent tumors: first results from MAPPYACTS molecular profiling trial towards AcSe-ESMART proof-of-concept study
Authors: Geoerger Birgit , Schleiermacher Gudrun , Pierron Gaelle , Lacroix Ludovic , Deloger Marc , Bessoltane Nadia , Harttrampf Anne Catherine , Michiels Stefan , Scoazec Jean Yves , Freneaux Paul , Paoletti Xavier , Delattre Olivier , Hoog-Labouret Natalie , Vassal Gilles 
Published: July 2017

In the area of precision medicine we initiated the multi-centric, international trials MAPPYACTS ‘A multicentric, prospective proof-of-concept study MoleculAr Profiling for Pediatric and Young Adult Cancer Treatment Stratification’ (NCT02613962) and AcSé-ESMART ‘European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors’ (NCT02813135).

Design: Patients with pediatric recurrent or refractory malignancy underwent on-purpose tumor biopsy or surgical resection for molecular characterization by whole exome and RNA sequencing. A molecular tumor board of scientists and clinician-scientists reviewed results to determine the biological significance of the alterations which were discussed with the treating physician in a clinical molecular tumor board. Patients were treated whenever possible in an adapted clinical trial or the hypothesis-driven ESMART proof-of concept trial for which comprehensive molecular profile at relapse was mandatory and an enrichment strategy was applied.

Results: From February 2016 to January 2017, 174 patients with a median age of 13 years (range, 1-32) were included in MAPPYACTS in 11 French centers. 39% had sarcomas, 25% brain tumors, 24% other solid tumor, 12% hematological malignancies. Currently, 104 patients have been completely analyzed and discussed. Of these, screening failed for 8.6% of patients. 95 patients underwent intervention by biopsy (72%), surgical resection (24%) or blood/bone marrow sampling (4%). Sufficient material was achieved in 81% of patients, 76 had whole exome, 68 RNA, 1 panel gene sequencing. For 76% of patients, at least one target was found that was considered ‘actionable’ and a total of 123 genomic alterations were decisional for the treatment suggestion. Alterations were CNA (56/123), somatic mutation (41), CNA + somatic mutation (11), gene fusion (6), germline mutation (3) germline mutation + CNA (3), CNA + fusion (2), expression (1).

Based on the detected alteration, 21 patients were included in the ESMART trial since it opened in August 2016, two of these patients were included in two different arms: with the CDK4/6 inhibitor ribociclib plus chemotherapy (1) or everolimus (5), DNA repair interfering combinations WEE1 inhibitor AZD1775 plus chemotherapy (4) and PARP inhibitor olaparib plus chemotherapy (1), dual mTOR inhibitor vistusertib alone (1) or with chemotherapy (5), or nivolumab and cyclophosphamide (6). 15 of the 23 inclusions were considered enriched as per detected alteration. 5 patients were included in other early clinical trials with a targeted agent. Updated results will be presented at the meeting.

Conclusion: MAPPYACTS shows the feasibility in a multicentric setting and confirms that actionable molecular alterations are frequently found in recurrent pediatric cancers. However few tumors have unique targetable driver events and proof-of-concept trials are crucial to explore innovate combination strategies in an enriched setting.

Citation Format: Birgit Geoerger, Gudrun Schleiermacher, Gaelle Pierron, Ludovic Lacroix, Marc Deloger, Nadia Bessoltane, Anne Catherine Harttrampf, Stefan Michiels, Jean Yves Scoazec, Paul Freneaux, Xavier Paoletti, Olivier Delattre, Natalie Hoog-Labouret, Gilles Vassal. European pediatric precision medicine program in recurrent tumors: first results from MAPPYACTS molecular profiling trial towards AcSe-ESMART proof-of-concept study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT004. doi:10.1158/1538-7445.AM2017-CT004