Inaugurated in June 2010, thanks to the support received from the ”la Caixa” Foundation, VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch is dedicated to complex clinical trials with drugs in early development (phase I and early phase II trials), focusing on novel targets. Occupying a total surface area of 1000 m², our Unit is located within the General Area of the Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus.

This privileged environment with direct access to patients, coupled with VHIO’s translational approach to research and superb scientific framework, has enabled our Unit to rapidly establish itself as one of the few comprehensive facilities in Europe to rapidly transform latest discovery into benefits for patients. Our UITM – CaixaResearch incorporates a multidisciplinary team comprised of medical oncologists, clinical trial coordinators and data managers, nurses and nurse technicians, pharmacists, as well as administrative personnel.

By promoting tight connectivity between oncology care and research we establish novel treatment models for patients with highly selective drugs, and advance insights into tumor types and how to treat them in an individualized way – getting the right therapy to the right patient, at the right time. As the statistics show, we continue to do so for an increasing number of patients.

For another year, we have had to rapidly adjust to overcome the many challenges posed by the COVID-19 pandemic. All our efforts have focused on successfully maintaining our clinical research activities and continuing to include patients in our clinical trials. During 2021, our Unit participated in 207 ongoing phase I clinical trials, 27 of which are Basket trials (a 6% increase compared with 2020).

Our facilities, coupled with our multidisciplinary clinical teams, enable us to continue to expand our portfolio of phase I studies with 551 patients enrolled (a 6% increase compared with 2020). This year we opened 66 new trials; 5 as Baskets.

Research carried out at our Unit by VHIO’s Early Clinical Drug Development Group, directed by Elena Garralda, centers on the development of new drugs based on the molecular profile of each tumor as well as the optimization of treatment regimens using combinations of new agents with those that already exist.

Reflective of VHIO’s purely translational model, our studies are also linked to several research lines led by other VHIO groups, thus connecting molecular biology and optimal tumor models with pharmacology and innovative clinical research. VHIO scientists collaborate in our trials to facilitate biomarker development, a deep understanding of the mechanism of action, as well as research into mechanisms of cancer drug resistance.

We also participate in VHIO’s Molecular Prescreening Program, that performs molecular analyses of patients’ tumors to select the best possible treatment with the experimental therapeutics available. Thanks to our Cancer Genomics Group (PI: Ana Vivancos) and their development of existing applications including an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD), and two NextGen Sequencers; MiSeq and HiSeq2500 (Illumina), we are equipped to perform faster and more precise mutational analyses of tumor suppressor genes as well as translocations and gene amplifications.

Excellent patient treatment and care as well as pioneering research is also made possible thanks to the collaboration of many other oncology professionals including our team of Clinical Research Oncology Nurses led by Ángeles Peñuelas, pathologists from the Vall d’Hebron University Hospital’s Molecular Pathology Department, radiologists and interventional radiologists, our Clinical Trials Office directed by Marta Beltran, Database Managers, VHIO’s Clinical Research Oncology Pharmacy Unit headed by Isabel Cidoncha, our Quality & Processes Unit headed by Gemma Sala, as well as many other healthcare specialists including dermatologists, cardiologists, and ophthalmologists.

• Early clinical drug development and translational research led by our UITM – CaixaResearch clinical investigators and VHIO researchers: expansion of our broad portfolio of promising novel anticancer therapies, across a balanced spectrum of studies, with special focus on first-in-human studies, novel-novel combinations, best-in-class compounds, and a new class of drugs.
• Perform complex trials such as organ dysfunction trials, Octopus as well as Basket studies, and link clinical research at this Unit to VHIO's preclinical and translational projects. We also collaborate with various other partners involved in drug development and translational research.
• Genomic medicine trials in early drug development: perform molecular analysis of patients' tumors in order to select the best possible treatment with the experimental treatments available, co-develop medical informatics applied to genomic medicine, and integrate preclinical and clinical research by incorporating novel drugs, new insights, and study design together with customized molecular diagnostics.
• Immunotherapy: our Unit's Task Force in early drug development of immunotherapeutics and cell signaling focuses on second generation immunotherapies, including new cytokines, bispecifics, intratumoral agents, immunomodulatory, and immune checkpoint inhibitors and combinations, as well as translational research in immuno-oncology.

• We have performed some of the most complex phase I trials, including those focused on molecularly-selected patient populations (trials in complex molecularly-selected patient populations Basket/Octopus trials), as well as trials in immuno-oncology.
• We have expanded our expertise in drugs targeting developmental pathways, cell signaling (ERK, MET, FGFR, RET, NOTCH, NTRK), and immunotherapy (LAG3, TIGIT, OX40, CD40, IDO, arginase inhibitors and engineered antibodies).
• Developed by VHIO's Cancer Genomics Group (PI: Ana Vivancos) we benefit from applications that enable us to generate faster results. These include an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD), and two NextGen Sequencers; MiSeq and HiSeq2500 (Illumina). We also co-develop customized molecular tests for VHIO's Molecular Prescreening Program, namely, disease-oriented mutation panels for our NGS platforms.
• We have established alliances with several pharma companies as the preferred site for testing their novel and most relevant therapies, including GlaxoSmithKline OCTC, Roche ImCORE, and Astra Zeneca/MedImmune Partner of Choice Network.
• Our investigators have successfully implemented the Basket of Baskets (BoB) trial which is a novel study in personalized medicine integrating cutting-edge molecular prescreening, the development of new diagnostic tests such as circulating DNA or Nanostring, with the testing of targeted therapies in populations of patients with identified molecular alterations and a high probability of benefiting from the selected treatments. This is an academic study, endorsed by the Cancer Core Europe (CCE) Consortium, and co-funded by pharmaceutical companies. We are engaged in ongoing and advanced negotiations with pharmaceutical companies to increase the number of modules.
• We have introduced Molecular Tumor Board meetings to discuss the most relevant genomic features of complicated cases and evaluate possible treatment options.
• We have launched an advanced cell-based therapy program, and are participating in several pharma sponsored trials to evaluate the role of TIL therapy. We are also exploring an academic TIL product in collaboration with Alena Gros (PI: VHIO’s Tumor Immunology & Immunotherapy Group).
• In collaboration with several other VHIO groups, we head our CaixaResearch Advanced Oncology Research Program (2020-2023), also supported by the ”la Caixa” Foundation.

Our Unit is ISO 9001:2015 certified and is part of the Medical Oncology Department of the Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus. It is thanks to the funding received from the ”la Caixa” Foundation, that our new Facility, the Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch- Clinical Research Onco-Hematology Unit opened last year, 2020. Equipped with all the very latest technologies, it enables us to provide even higher quality in pharmaceutical care and continue to respond to all regulatory requirements.

We focus on two main areas of clinical research in oncology:

Oncology Pharmaceutical Care Program

Our team of expert pharmacists are specialized in hospital and oncology pharmacy. The Unit’s laboratory technicians prepare cytostatics and other parenteral therapies used in clinical trials, as well as closely monitor and follow-up our patients.

Pharmacological Research in Oncology Support Program

This program is directed by our team of pharmacists and laboratory technicians specialized in clinical trials. They are responsible for the management of study supplies including storage, dispensation, and traceability control.

In 2021 they managed drugs used in 609 active clinical trials in oncology & hematology, and 11,719 resupply deliveries/clinical trial supplies receptions. Our cutting-edge system for controlling storage temperature -performing electronic temperature recordings every 5 minutes daily- displays readings on computers equipped with audiovisual alarms as well as an around-the-clock SMS alert system for monitoring and reporting temperature deviations.

Regarding the design and validation of our Unit’s drug preparation process traceability system, we ensure qualitative and quantitative quality control of our computerized system.

In 2021 our dispensing staff actively participated in 280 pre-study visits, 280 initial visits, 2014 monitoring visits, 160 close-out visits, and also successfully passed 8audits, and 2 ISO inspection.

Additionally, 44,261 clinical trial drugs have been dispensed and validated by our pharmacists, 12,969 of which were for oral administration, 1,230 for IM/ subcutaneous administration, and 29,974 for IV administration. A total of 234 Standardized Dispensing Procedures for clinical trials have been drawn up and we have performed 985updates of these procedures due to subsequent amendments to protocols or pharmacy manuals. 103 storage temperature data reports have also been prepared by our dispensing team.

Preparations of cytostatics, monoclonal antibodies and other parenteral antitumor drugs for clinical trials totaled at 29,974. We also included 363 antineoplastic therapeutic schedules in our prescription software.

Our Pharmaceutical Care Program for patients enrolled in phase I clinical trials: we performed 967 visits, 447 screenings, 967 C1D1s, and 1,050 follow-ups, also compiling patient diaries and/or instructions for patients (in the absence of documentation provided by the respective sponsor).

• Excellence in the services that we provide to clinical oncology research programs through optimal efficacy, efficiency and safety.
• Management, dispensing, preparation and administration of clinical study drugs according to protocol specifications. Ensure traceability of the entire circuit with the development and implementation of new software.
• Maximized control of storage temperature of samples and preparations.
• Optimal use of a computerized program, IPharma-FUNDANET®, for the management of clinical trial supplies.
• Provision of a pharmaceutical care program for patients in phase I, II and III studies treated with orally administered medicines to improve safety, compliance and the efficacy of these therapies.
• Successful sponsor audits as well as inspections carried out by regulatory authorities.

• Replacing paper medical orders, we have implemented electronic prescription ordering for IV administration medication in our site prescription software.
• We have developed new traceability software that includes global pharmacotherapeutic processes; the prescription, validation, dispensing, preparation and administration of drugs in the oncology and hematology clinical trial setting.
• Our Unit provides clinical and technical support for the prescription, preparation, and administration of cytostatics in clinical trials, as well as e-records of usage and timings.
• Qualitative and quantitative quality control of all parenteral anticancer preparations to guarantee patient safety and protocol compliance.
• ISO9001:2015 certification renewed. Successful sponsor audits, regulatory inspections, and participation in the renewal of VHIO’s Phase I Unit reaccreditation.

Our VHIOTECA Unit was created in 2021 to support researchers for the obtention, registration and preservation of biological samples other than tumoral tissue (plasma, feces, saliva, etc.) from cancer patients, and facilitate the use of these samples in research projects.

The use of liquid biopsy testing in cancer patients for the identification of new biomarkers of response and resistance to therapy, coupled with its incorporation in clinical research projects requiring plasma, have led to a significant increase in the extraction of blood samples from cancer patients.

This activity requires a suitable structure, dynamization of circuits and the optimization of resources. For this reason, our first objectives are to consolidate existing circuits and processes so that they are consistent and reliable, and to ensure the optimal use of samples in the best possible conditions. We are also committed to supporting VHIO researchers in setting up new projects and collaborations that require the use of these types of samples.

Another area of growing interest of research in clinical oncology is the study of the microbiome during tumor development and progression, especially in colorectal cancer. These studies require the collection and genomic and molecular analysis of stool samples as well as the completion of questionnaires for subsequent epidemiological studies. To support our researchers, we aim to create a new sample and data collection circuit that facilitates the development and execution of projects.

Our team comprises clinical research oncology nurses specialized in specific tumor types, technical staff for sample processing and registration (sample managers), and technical support staff for sample logistics and management, database creation and maintenance.

VHIO’s Molecular Prescreening Program

Since 2017 our Head of Unit, Susana Aguilar, has coordinated molecular prescreening at VHIO, and now collaborates closely with the program’s Research Support Technician, Jenifer González. This program is co-led by Ana Vivancos, Elena Garralda, Paolo Nuciforo, and Rodrigo Dienstmann, PIs of our Cancer Genomics, Early Clinical Drug Development, Molecular Oncology, and Oncology Data Science (ODysSey) Groups, respectively.

Consolidation of existing circuits:

• Provide support to researchers in the extraction, registration and storage of samples (mostly plasma) and database maintenance.
• Standardize protocols and establish Standard Operating Procedures (SOPs).
• Maintain optimal registration and archiving of the informed consent of the patients.
• Creation and consolidation of new circuits: establish new circuits for the collection of different plasma and tumor samples (e.g. feces, saliva, breast milk, etc.), sample and patients’ data, and tailor them accordingly to meet the requirements and specificities of research projects.
• Research support: collaborate with different teams of clinical and preclinical researchers to help set up new projects and collaborations using existing or new samples.

Active participation in the following international projects:

• EUCANCan: a federated network of aligned and interoperable infrastructures for the analysis, management and homogeneous sharing of genomic oncology data for Personalized Medicine.
• Molecular Tumor Board (MTB) of the Cancer Core Europe (CCE) Consortium’s Baskets of Baskets (BoB).
• Genomics Evidence Neoplasia Information Exchange (GENIE) Project of the American Association for Cancer Research (AACR).