Over recent years, several advances have led to the more effective treatment of non-prostate genitourinary (GU) malignancies. Immunotherapy (IO) is proving to be increasingly important for the treatment of both bladder and kidney cancer. In bladder cancer, combining antibody drug conjugates (ADCs) and IO has changed the first-line treatment landscape of patients with metastatic disease. IO has become a standard treatment for high risk bladder cancer patients in the adjuvant setting, with two IO treatments demonstrating improved progression-free survival (PFS).

In kidney cancer, immune-based combination therapy, or IO plus antiangiogenics, are now considered as standard first-line treatment. Also, HIF2α inhibitors have demonstrated their role in second line metastatic disease. We are now studying novel combinations including HIF2α inhibitors and other immunomodulators to improve OS. We are moving these drugs to the adjuvant setting to demonstrate that they are more active when used earlier in the disease evolution. In collaboration with Danna-Farber Cancer Institute we are exploring possible predictive biomarkers of response to HIF2α inhibitors.

In close collaboration with the Urology Department at the Vall d’Hebron University Hospital (HUVH), we are participating in phase I clinical studies with drugs targeting FGFR and Nectin 4. We are also evaluating ADCs with new intravesical drug delivery devices that provide local and sustained release in patients with non-muscle invasive bladder cancer who experience relapse or progress despite adequate intravesical Bacillus Calmette-Guerin (BCG) therapy, for whom early radical cystectomy is recommended. These new treatments and devices are intended to preserve the bladder.

Theragnosis represents an innovative treatment approach in prostate cancer based on administering radio-ligands using beta and alpha emitters. This therapy is now moving to other GU malignancies like kidney cancer.

We also work together with other renowned research centers including the Cleveland Clinic (Ohio, USA), University of California, San Francisco (California, USA), Fred Hutchinson Cancer Center (Seatle, USA), The Netherlands Cancer Institute (Amsterdam, The Netherlands), and participate in studies carried out in partnership with the Gustave Roussy Institute (Paris, France), Barts Health NHS Trust – Hospital (London, UK), and Kantonsspital St. Gallen (Switzerland).

Initiated in May last year, CARE1 is a European project coordinated by Gustave Roussy. Focused on pragmatic clinical trials, and leveraging a unique academic European network, CARE 1 aims to improve the first-line treatment of patients with metastatic kidney cancer by implementing a routine biomarker. Our participation in this project is supported by the CRIS Cancer Foundation and the EU Horizon Europe research and innovation programme.

Supported by funding received from the Spanish Society of Medical Oncology (SEOM), we are coordinating a national study to identify predictive biomarkers of response to first-line therapy in renal cell carcinoma (RCC). Througn a Spanish Genitourinary Oncology Group (SOGUG) grant, we also participate in a project devoted to paired tumor biopsy analysis.

In 2023, we launched the CHECKYMID trial to prospectively investigate the role and safety of IO in the treatment of patients with cancer (RCC, bladder, lung, or melanoma) and affected by immune-mediated inflammatory diseases (IMIDs). We coordinate this study in collaboration with the rheumatology, digestive and dermatology teams at HUVH. In this first year of the project, we have enrolled 6 patients.

We have consolidated our center as a reference for clinical and translational research into primary brain tumors, leading to first author oral presentations in clinical studies for tovorafenib, a drug that has received approval by the FDA for pediatric low-grade glioma (ESMO Congress 2024); and ataxia telangiectasia and Rad3-related protein (ATR) inhibitor tuvusertib with activity in isocitrate dehydrogenase (IDH) mutant gliomas (EANO 2024). Tuvusertib will be further evaluated in an investigator-initiated trial (IIT) that will be co-led by VHIO.

We continue to lead the Adolescent Working Group of the GEINO Spanish cooperative group for research in neuro-oncology and have participated in the updating of the clinical guidelines for low-grade glioma, that were the first national guidelines to incorporate the results of the INDIGO trial. We have partnered with cure51, and other oncology centers of excellence, in a pioneering public-private collaboration to leverage a cohort of patients with long-term survival, after a diagnosis of glioblastoma, to discover new therapies for this and other hard-to-treat tumors. Aimed at truly understanding the impact of the disease on patients and their families, we are developing an electronic tool to empower patients with gliomas to self-report their quality of life.

In the sarcoma field, we have continued our collaboration with the Spanish Sarcoma Group (GEIS) and EURACAN (European Reference Network (ERN) for rare tumors).

Together with GEIS, we have been able to perform several phase I academic trials including GEIS 52/69- IMMUNOSARC, a study exploring the combination of nivolumab and sunitinib as well as vivolumab, with tailored chemotherapy in the first-line treatment of specific sarcoma subtypes with good results, that have allowed the transition to and completion of the phase II study in 2024.

In collaboration with Laura Soucek’s lab and Peptomyc (a spin-off from VHIO and ICREA), the Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center and Oregon Health and Science University, and thanks to the support of the Osteosarcoma Institute, Curing Kid’s Cancer Foundation, The Morgan Adams Foundation and the Kirsten Ann Carr Fund, the sarcoma team has launched OSTEOMYC. OSTEOMYC is an academic phase II pilot study testing the activity of OMO-103, currently the only MYC inhibitor available, in patients with advanced/metastatic osteosarcoma from 12 years old. The planned correlative studies, including the exploration of a predictive signature developed during the phase I trial, will help us to understand the role of the drug in this population and open the field to future development. In addition, this will be our first VHIO promoted trial to opt for the FAIR for AYA Stamp recognition by ACCELERATE, a platform aimed at accelerating the process of evaluating innovative therapies and introducing them in standard cancer care in children and adolescents.

Another of our highlighted interests is the use of liquid biopsy in sarcoma. The INSIGHT trial is a phase 3, randomized, open-label study designed to evaluate the efficacy of ripretinib vs. sunitinib in patients with advanced GIST previously treated with imatinib and who harbor KIT exon 11 + 17 and/or 18 secondary mutations, detected by ctDNA. This study has the potential of defining the implementation of liquid biopsy in GIST treatment. The basis for this trial comes from recent seminal works in which we have been actively involved or taken a leadership role (Serrano et al, Ann Oncol 2023; Heinrich et al, Nat Med 2024). In the same vein, our group has been actively involved in the clinical development of vimseltinib, a novel CSFR1 inhibitor, which will be the first therapy approved for tenosynovial giant cell tumor (TGCT) (Gelderblom et al, Lancet 2024).

Our Serum Bank now includes most of the tumor types that we study (CNS tumors, GIST; renal cell carcinoma and bone sarcoma), and we will continue to collect samples from our patients.

We have consolidated our Unit for Adolescent and Younger Adults (AYAs) for patients aged between 16 and 25 years old. This program collects data for the development of new treatments for tumors that occur during adulthood but are predominantly seen in pediatric populations, and vice versa. Led by both adult and pediatric oncologists, this Unit is initially treating patients with CNS tumors, sarcoma, and testicular tumors, but also aims to include other tumor types and advance insights into late cancer therapy toxicity. Since we created the AYAs Unit more than 80 patients have been treated and evaluated.

Regarding tumors of unknown primary (CUP), we are collaborating with investigators at the Josep Carreras Leukaemia Research Institute led by Manel Esteller. By employing multi-omics (genomics, transcriptomics and epigenomics) to characterize the molecular features of 500 CUP cancer cases, we aim to deepen our understanding of the molecular mechanisms governing the development of these tumors. Supported by the Carlos III Health Institute (ISCIII), we lead and coordinate the IMPaCT-GENóMICA precision medicine program to advance the diagnosis of CUP tumors. We are also collaborating with VHIO’s Computational Immunogenomics Group led by Francisco Martínez Jiménez, to understand the genomic basis of tumorigenesis and its interplay with the immune system.

In germ cell tumors, we are leading a late relapse project in Spain (RELAGERM). This project is part of an international initiative led by the Instituto Oncologico della Svizzera Italiana. Additionally, we are leading a national study evaluating the efficacy and safety of cisplatin-based chemotherapy in patients over 40 years of age diagnosed with metastatic germ cell tumors.

Dedicated to promoting education and exchange, in 2024 we welcomed seven fellows from Spain and abroad for 3-month short stays.