Abstract CT093: Cancer Core Europe - Basket of Baskets - first results from module 1: Atezolizumab in genomically selected populations

Abstract Background: Platform studies optimize molecular profiling offering matched therapies to selected patients (pts). Prior studies have reported the activity of antiPD1/PD-L1 in solid tumor pts with high TMB without considering the underlying genetic background. Methods: Basket of Baskets (NCT03767075), is a platform trial from Cancer Core Europe. Pts underwent molecular profiling (iPROFILER) and were assigned to one of the modules (iBASKET). In module 1 arms, IO-naïve pts received atezolizumab according to alterations in DNA repair genes or high/intermediate TMB (see table). Pts provided paired biopsies, serial plasma, and stool for correlative studies. Primary endpoint: overall response rate at 12 weeks (ORR). This module used a Bayesian design. Arm size varied from 5 to 20 pts to identify an ORR from 30-50%. Exploratory endpoints: (i) correlation of response and clinical benefit with alterations observed by tumor WES, RNA-Seq, and proteomics, (ii) correlation of response with serial cfDNA and plasma proteomics. Results: Among 84 pts included in arms 1A-1F, 79 were evaluable for response. Higher ORR and best ORR were observed in arm 1B and 1D with high TMB (see table). Nine additional responses were observed after 12 weeks. Responses were observed in pts with colorectal (4), bladder (2), lung (2), breast, ovarian, gastric, adrenocortical, anal, salivary gland cancer, basal cell carcinoma and carcinoma of unknown primary (1 each). Preliminary data suggests that early changes in cfDNA and plasma proteomics correlate with clinical benefit. WES and RNA-Seq data are expected for the meeting presentation. Conclusion: Higher response rate was observed in arm 1B and 1D high TMB, including pts with rare tumors and without reimbursed indication. Initial evidence suggests a correlation of cfDNA and plasma proteomics dynamics with clinical benefit. Citation Format: Irene Brana, Christophe Massard, Frans Opdam, Richard D. Baird, Luigi De Petris, Richard Schlenk, Claudio Vernieri, David Tamborero, Shubha Anand, Etienne Rouleau, Adria Lopez, Nikos Demiris, Paolo Nuciforo, Elena Provenzano, Daniel Huebschmann, Katrin Pfütze, Maria Pernemalm, Daniel Vis, Ana Vivancos, Valtteri Wirta, Peter Horak, Omar Saavedra, Marloes van Dongen, Emily Barker, Susana Aguilar, Elena Chavarria, Xenia Villalobos, Marta Rotxes, Arantxa Romero, Francisco Martínez-Jiménez, Alena Gros, Anna Pedrola, Cristina Viaplana, Neeltje Steeghs, Elena Garralda, Cancer Core Europe - Basket of Baskets study team, Alejandro Piris, Karim Fizazi, Fabrice Barlesi, Karen Barker, Michiel Heijden, Wilbert Zwart, Filippo de Braud, Elias Arner, Janne Lehtiö, Michael Baumann, Stefan Fröhling, Josep Tabernero, Javier Carmona, Jordi Rodon. Cancer Core Europe - Basket of Baskets - first results from module 1: Atezolizumab in genomically selected populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT093.