Our Molecular Prescreening Program is powered by one of our Institutional Supporters and Patrons, the Fundación FERO . FERO’s Institutional Advanced Molecular Diagnostics Program (DIAMAV) catalyzes precision medicine at VHIO. Over the last decade, this program has provided access to advanced molecular diagnostics to more than 8,000 cancer patients, and is critical in matching targeted therapeutic approaches with hundreds of clinical trial opportunities.
This pioneering program, also counting on the support and expertise provided through our Research Unit for Molecular Therapy of Cancer (UITM) - CaixaResearch, is co-led by VHIO’s Ana Vivancos, Paolo Nuciforo, Elena Garralda, and Rodrigo Dienstmann, Principal Investigators of our Cancer Genomics, Molecular Oncology, Early Clinical Drug Development, and Oncology Data Science (ODysSey) Groups, respectively.
Serving as a Transversal Clinical Trials Core Service, our expert team focuses on the clinical implementation of advanced molecular diagnostics to optimize the selection of therapies for patients being considered for enrollment in clinical trials, as well as continued medical education on emerging cancer biomarkers for precision cancer therapy. By advancing molecular profiling in patients, personalized treatment strategies based on the genomic or pathologic profile of each individual patient can be more effectively matched to the molecular makeup of their respective disease.
Our researchers and clinical investigators identify specific molecular risk factors and better predict the potential efficacy of specific agents tailored to each particular tumor. These insights better guide our multidisciplinary teams to assess and establish patients’ suitability for inclusion in early phase clinical trials conducted at VHIO’s UTIM – CaixaResearch.
It is thanks to the backing received from FERO that our Molecular Prescreening Program continues to establish itself as a reference in prescreening and oncogenomics in Europe. Thanks to our cutting-edge technologies and platforms, we continue to extend the promise of precision medicine in oncology to an increasing number of individuals. In 2021, we performed tumor molecular profiling in 1,138 cancer patients as candidates for enrolment in clinical trials.
In short, FERO’s Institutional Program enables us to lead and run such a comprehensive program. In so doing, we continue to ensure that more of our patients can ultimately benefit from our powerful technology programs and approaches, further advance research into the more effective and less invasive tracking of cancer by liquid biopsy, and develop cancer diagnostics for the early detection of disease.
Cancer is a leading cause of death worldwide, with an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths occurred in 2020. While survival rates continue to improve, there are still many tumor types with no effective treatments. Clinical trials are crucial to identifying and developing novel therapies against cancer and are only possible at VHIO thanks to the continued support received from one of our Institutional Supporters and Patrons, the ”la Caixa” Foundation.
Building on the successes of the two previous VHIO -”la Caixa” Institutional 3-year Programs, the CaixaResearch Advanced Oncology Research Program (2020-2023), continues to spur our development of more potent and precise anti-cancer medicines. It also enables us to fortify existing research lines, initiate new projects, and lead frontier research in some of the most relevant and rising focus fields in precision oncology; those that show particular promise in solving the multiple questions that stand in the way of more effectively combating this disease.
Our Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, also supported by the ”la Caixa” Foundation, allows us to pursue our transformative research lines aimed at unpicking the complex role that the microbiome plays in cancer development, drive ‘big data’-derived insights, develop and integrate cutting-edge platforms incorporating bioinformatics, biostatistics and machine learning applications in cancer prognosis and prediction, as well as harness the potential of Artificial Intelligence (AI) in the development of individually matched therapies.
Clinical trials performed at this Unit have led and/or contributed to the approval of more than 30 anti-cancer agents by either the U.S. Food and Drug Administration (FDA), or the European Medicines Agency (EMA), or both. It is thanks to the support received that we can continue to advance and apply novel anti-cancer approaches and armory including liquid biopsy, RNA expression analysis, immune-based therapies, bispecific antibodies, oncolytic virus, and intratumoral therapy. These efforts are driven thanks to the expertise of several VHIO groups and teams including our Early Clinical Drug Development, Cancer Genomics, Molecular Oncology, Oncology Data Science (ODysSey) Groups, led by Elena Garralda, Ana Vivancos, Paolo Nuciforo, and Rodrigo Dienstmann, respectively.
Within the scope of our CaixaResearch Advanced Oncology Research Program, Elena Garralda's team has performed several clinical trials with patients selected on molecular alterations: mutations in AKT1, EGFR, IDH1, ALK, ROS1, BRAF, NRAS, KRAS, FGFR1 and 2, MET, HER2, HER3, RET; ATM; BRCA, amplifications in HER2, AKT 1, 2, and 3, FGFR1, MET, NOTCH1-4, rearrangements of NTRK1-3 ROS1, ALK, BRAF, RSPO2/3, RET, NRG and FGFR1-3.
The matched dedication of our clinical and translational investigators across all VHIO programs and groups, as well as our transversal clinical trials core services enables us to expand our portfolio of clinical studies and include an increasing number of patients, year-on-year.
Importantly, all of our teams have continued to rapidly overcome the many challenges posed by the COVID-19 pandemic. They have successfully maintained our clinical research activities and continued to include patients in clinical studies – even reporting increased activity in some areas compared to previous years. In 2021, our Unit participated in 207 ongoing phase I studies, 27 of which are Basket trials (a 6% increase compared with 2020). This year, 66 new trials opened; 5 as Baskets, with 551 patients enrolled.
Among the many highlights in 2021 was the expansion of the Basket of Baskets (BoB). This academic study, endorsed by CCE, integrates molecular prescreening, the development of new diagnostic tests such as circulating DNA, with the assessment of targeted therapies in populations of patients who, matched to specific molecular alterations, will be most likely to benefit from these treatments. During 2021 we opened a new module targeting FGFR pathway alterations as well as searched for funding for new modules.
Considering the successes of the very first VHIO-BBVA Foundation Program on Tumor Biomarkers Research that launched back in 2011, VHIO and the Fundación BBVA - one of our Institutional Supporters and Patrons, - renewed their agreement in in 2018. Building on the achievements of the first program, our 4-year Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI), centers on advancing research into the natural mechanisms governing how T lymphocytes react to cancer and how to use these anti-tumor responses to develop more personalized and potent immune-based therapies and treatment strategies.
Representing an important forward step in advancing agents that inhibit checkpoint regulation of the immune system, this VHIO Institutional Program aims at achieving a deeper understanding of mechanisms of resistance and response to these therapies, and prioritizes the early clinical drug development of those therapies and combinations that show most promise.
Under the leadership of our Director, Josep Tabernero, CAIMI counts on the expertise of Elena Garralda, Director of our Research Unit for Molecular Therapy of Cancer (UITM) - CaixaResearch, who heads up the program’s clinical research, and Alena Gros, Principal Investigator of our Tumor Immunology & Immunotherapy Group, who leads its translational research. It also relies on our Molecular Prescreening Program, co-led by Ana Vivancos, Paolo Nuciforo, Elena Garralda, and Rodrigo Dienstmann, Principal Investigators of VHIO’s Cancer Genomics, Molecular Oncology, Early Clinical Drug Development, and Oncology Data Science (ODysSey) Groups, respectively.
Over the past three years, CAIMI has enabled the development of various translational projects linked to the early clinical development phases of immunotherapy. Just some focus areas include the development of cell-based therapies such as killer T cells for non-responders to current immunotherapies, and characterizing hyperprogressive disease with immunotherapy to advance insights into this phenomenon. In 2021, we established a radiomic signature to predict response to immunotherapy, led by Raquel Perez-Lopez, Principal Investigator of our Radiomics Group, and are now exploring how this correlates with the evolution of disease in patients.
Importantly this year, Alena Gros’ and Elena Garralda’s teams finalized the clinical grade validations of tumor-infiltrating lymphocytes expansion for the treatment of certain cancer patients at the Vall d’Hebron University Hospital (HUVH), in collaboration with the Banc de Sang i Teixits - BST (Blood and Tissue Bank), a public agency of the Catalan Department of Health.
Most recently, they received authorization from the AEMPS to initiate a phase I clinical trial, NEXTGENTIL-ACT, to study the safety and tolerability of neoantigen-selected tumor-infiltrating lymphocytes (TILs) for patients with solid tumors refractory to standard therapies. By enriching for neoantigen-reactive lymphocytes, the aim is to fortify the efficacy of TIL therapy in epithelial cancers. Patient recruitment is now underway.
Aimed at accelerating cancer discovery through team science, VHIO’s multidisciplinary teams, coordinated by our Scientific Management Area, also work together as dedicated Task Forces (TFs) that have been established in line with VHIO’s strategic plan and core research priorities.
Our TFs comprise preclinical and translational researchers, clinical investigators and medical oncologists, pathologists, other medical disciplines, clinical research nurses, data curators and study coordinators, as well as project managers, among others.
Covering breast, colon, gastroesophageal, kidney, melanoma, neuroendocrine, rectal, pancreatic, prostate, and gynecological cancers, onco-imaging, as well as patients’ involvement in research, VHIO's TFs regularly convene to synergize efforts, boost collaborations among groups and between specialists, and continuously revise patient circuits, sampling and ethics toward advancing cancer science and precision medicine. The internal organization of these expert teams varies depending on their size, workflow, participants, and activities. They each have an appointed Chair and are coordinated by an allocated project manager to set respective agendas, compile meeting minutes, follow up on action points/ tasks, and work together to establish alignments, interactions and synergies across all TFs.
Illustrative of VHIO’s commitment to teamwork, clinical researchers from other medical specialties across Vall d’Hebron and/or other local hospitals in Catalonia, as well as investigators from the Vall d’Hebron Barcelona Hospital Campus and other research institutions, actively contribute to the activities of our TFs.
We seek to identify additional areas that require task force teams. As an example, in 2021 we launched a new TF dedicated to patients that aims to involve and engage patients, their families and caregivers in our research. Also in the planning are potential transversal TFs focused on additional areas including cancer prevention and early detection in alignment with ongoing policies and activities such as the European Code Against Cancer and the Cancer Mission.