Search

The current COVID-19 pandemic challenges oncologists to profoundly re-organize oncological care in order to dramatically reduce hospital visits and admissions and therapy-induced immune-related complications without compromising cancer outcomes. Since COVID-19 is a novel disease, guidance by scientific evidence is often unavailable, and impactful decisions are inevitably made on the basis of expert opinions. Here we report how the seven comprehensive cancer centers of Cancer Core Europe have organized their healthcare systems at an unprecedented scale and pace to make their operations 'pandemic proof'. We identify and discuss many commonalities, but also important local differences, and pinpoint critical research priorities to enable evidence-based remodeling of cancer care during the COVID-19 pandemic. Also, we discuss how the current situation offers a unique window of opportunity for assessing the effects of de-escalating anticancer regimens, which may fast-forward the development of more-refined and less-toxic treatments. By sharing our joint experiences, we offer a roadmap for proceeding and aim to mobilize the global research community to generate the data that are critically needed to offer the best possible care to patients.

Adaptive designs; Umbrella protocols; Basket protocols Dissenys adaptatius; Protocols de paraigua; Protocols de cistell Diseños adaptativos; Protocolos de paraguas; Protocolos de cesto Cancer treatment has made significant strides towards the promise of personalized medicine. Recent scientific advances have shown that there are numerous genetic deregulations that are common in multiple cancer types, raising the possibility of developing drugs targeting those deregulations irrespective of the tumour type. Precision cancer medicine was born out of accumulated evidence matching targeted agents with these tumour molecular deregulations. At the same time, the therapeutic armamentarium is rapidly increasing and the number of new drugs (including immune-oncology agents) entering drug development continues to rise. These factors, added to strong collaboration with regulatory agencies which have approved novel agents based on data obtained from Phase 1/2 trials, have led to unprecedented evolution in the design of early stage clinical trials. Currently, we have seen rapid Phase 1 dose escalation trials followed by remarkably large expansion cohorts, and are witnessing the emergence of new trials, such as adaptive studies with basket and umbrella designs aimed at optimizing the biomarker-drug co-development process. Alongside the growing complexity of these clinical trials, new frameworks for stronger and faster collaboration between all stakeholders in drug development, including academic institutions and frameworks, clinicians, pharma companies and regulatory agencies, have been established. In this review article, we describe the main challenges and opportunities that these new trial designs may provide for a more efficient drug development process, which may ultimately help ensure that precision cancer medicine becomes a reality for patients

TPS3151 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.

Nature Reviews Cancer 17, 254–268 (2017) In the online html version of this article, Joan Seoane's affiliations were not correct. He is also a member of the EurOPDX Consortium and is at the Vall d'Hebron Institute of Oncology, 08035 Barcelona, the Universitat Autonoma de Barcelona, 08193 Bellaterra,and the Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Spain.

Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and the implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. This Opinion article discusses aspects of PDX modelling that are relevant to these questions and highlights the merits of shared PDX resources to advance cancer medicine from the perspective of EurOPDX, an international initiative devoted to PDX-based research.

Counteracting high attrition rates in anticancer drug development and providing optimal therapeutic management of cancer patients require preclinical models that properly recapitulate the complexity and diversity of human tumours. Patient-derived cancer xenografts (PDXs), developed by transplanting human tumor fragments into immunodeficient mice, retain the idiosyncratic characteristics of different tumors from different patients. The possibility of population-scale correlations between therapeutic response in PDXs and extensive, multidimensional molecular annotation has enabled the identification of several sensitivity and resistance biomarkers in a number of different tumor types, with immediate clinical relevance. To effectively recapitulate and therapeutically interrogate through patient-derived models the heterogeneity that typifies human cancer, 13 European cancer centres and university hospitals joined forces in 2013 to start EurOPDX, an academic research consortium that now gathers 19 institutions throughout Europe and in the US. EurOPDX includes world-renowned experts at the forefront of research in basic, preclinical, translational and clinical oncology across multiple pathologies, and displays a wide range of expertise in technological platforms. The primary goal of the Consortium is to maximize exploitation of PDXs and other patient-derived cancer models for cancer research by: (i) integrating institutional collections into an organic, multicentre collection of patient-derived models, now reaching 2,000 subcutaneous and orthotopic models for 30+ different pathologies (www.europdx.eu); (ii) defining common operating procedures to improve and standardize molecular and pharmacologic characterization of the models; (iii) sharing models within and outside the consortium to perform collaborative precision oncology “xenopatient” trials, to discover predictive biomarkers, new targets, and new strategies to overcome drug resistance. Towards these objectives, the EC granted 5 million euros under the H2020 programme for a “EurOPDX Distributed Infrastructure for Research on patient-derived Xenografts" - EDIReX EU project n. 731105, starting on February 2018. By teaming up with other key academic, technological and SME partners, our goal with EDIReX is to establish a cutting-edge European infrastructure offering transnational access to PDX resources to academic and industrial cancer researchers, including the distribution of cryopreserved samples to third parties, the structured biobanking of user-developed models, and the performance of drug efficacy studies. We will provide an overview of the current achievements of the Consortium and the objectives of the EDIReX project. Citation Format: Enzo Medico, Mohamed Bentires-Alj, Andrew V. Biankin, Alejandra Bruna, Annette T. Byrne, Carlos Caldas, Robert B. Clarke, Georges Coukos, Olivier Elemento, Manuel Hidalgo, Giorgio Inghirami, Steven de Jong, Jos Jonkers, Ales Krenek, Eleonora Leucci, Gunhild Mari Maelandsmo, Michaela Th. Mayrhofer, Terrence F. Meehan, Simone P. Niclou, Pier Giuseppe Pelicci, Alejandro Piris-Gimenez, Leo Price, Sergio Roman-Roman, Livio Trusolino, Luca Vezzadini, Alberto Villanueva, Emilie Vinolo, on behalf of the EurOPDX Consortium. The EurOPDX EDIReX project: Towards a European research infrastructure on patient-derived cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 985.