Basket of baskets (BoB): A modular, open label, phase II, multicenter study to evaluate targeted agents in molecularly selected populations with advanced solid tumors.

Irene Brana Vall d'Hebron Institute of Oncology, Barcelona, Spain info_outline Irene Brana, Christophe Massard, Richard D. Baird, Frans Opdam, Richard F. Schlenk, Luigi De Petris, Claudio Vernieri, Elena Chavarria, Elena Garralda, Ruud van der Noll, Ana Vivancos, Lodewyk F. A. Wessels, Jose-Ezequiel Martin, David Tamborero, Rodrigo Dienstmann, Gerrit A. Meijer, Susana Muñoz, Alejandro Piris-Giménez, Fabien Calvo, Jordi Rodon

Authors Irene Brana Vall d'Hebron Institute of Oncology, Barcelona, Spain info_outline Irene Brana, Christophe Massard, Richard D. Baird, Frans Opdam, Richard F. Schlenk, Luigi De Petris, Claudio Vernieri, Elena Chavarria, Elena Garralda, Ruud van der Noll, Ana Vivancos, Lodewyk F. A. Wessels, Jose-Ezequiel Martin, David Tamborero, Rodrigo Dienstmann, Gerrit A. Meijer, Susana Muñoz, Alejandro Piris-Giménez, Fabien Calvo, Jordi Rodon Organizations Vall d'Hebron Institute of Oncology, Barcelona, Spain, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif, France, University of Cambridge, Cambridge, United Kingdom, NKI-AVL, Amsterdam, Netherlands, National Center of Tumor Diseases Heidelberg, Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany, Dep of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, The Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Amsterdam, Netherlands, Cancer Genomics Lab and Molecular Pathology Lab, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Department of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, Netherlands, CRUK Cambridge Centre, Cambridge, United Kingdom, Karolinska Institutet, Stockholm, Sweden, Oncology Data Science Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Netherlands Cancer Institute, Amsterdam, Netherlands, Vall d'Hebron University Hospital, Barcelona, Spain, Fundacio Privada Institut Oncologica Vall Hebron, Barcelona, Spain, INSERM, Paris, France, Vall d’Hebron University Hospital Institute of Oncology (VHIO), Barcelona, Spain Abstract Disclosures Research Funding Other Pharmaceutical/Biotech Company Background: Basket trials with targeted agents can show high response rates for tumors with specific molecular profiles, granting extension of the label of some drugs. In other cases, study results were disappointing, likely due to the rarity of molecular alterations, limits in trial design and the difficulties in applying molecular tumor profiling in the clinical setting. Methods: Basket of Baskets (BoB), NCT03767075, aims to bridge the gap between Academic Genomics and clinical applications (ready-to market multi-marker Companion Diagnostics) by providing a sustainable and adaptable (to new technologies, markers, and therapeutic agents) platform for co-development of drug/companion diagnostic. BoB is a novel platform trial from Cancer Core Europe, a recently established sustainable European network for innovative cancer research. This protocol has two parts: (1) Part A includes a molecular profiling program for subjects with advanced solid tumors (iPROFILER), a variant annotation tool, and a molecular tumor board to select the most appropriate treatment. It also enables testing/developing companion diagnostics linked with the therapeutic part (part B). (2) Part B includes iBASKET, a modular multi-arm basket trial for subjects with tumors harboing selected molecular alterations. Each module is focused on a certain molecular pathway or on certain molecular alterations that may confer sensitivity to the study drug or study drug combination evaluated in that module/arm. The current version of iBASKET (Module 1- Atezolizumab in genomically-selected patients) is open for enrollment for patients with advanced neoplasms bearing one of the following alterations: Arm 1A: BRCA1 or BRCA2 ; Arm 1B: MLH1 , MSH2 , MSH6, PMS2 ; Arm 1C: POLE , POLD1 mutations; Arm 1D: hypermutated tumors; Arm 1E: other mutations in DNA-repair genes; Arm 1F: PDL1 gene amplification. All patients enrolled in Module 1 will receive single-agent atezolizumab. New Modules for genomically selected populations can be added through amendments. Our final aim is to achieve drug repurposing of treatments, co-develop multi-marker companion diagnostics and a large database of knowledge in Precision Medicine. Clinical trial information: NCT03767075