Targeted therapies improve efficacy in early-phase clinical trials driven by molecular patient selection

Researchers at VHIO have published an article in the journal European Journal of Cancer on the evolution of targeted therapies in early-phase clinical trials. The study shows a progressive improvement in the efficacy of these therapies in phase 1 and 2 clinical trials, especially when treatments are assigned according to the molecular profile of the tumor.

Based on data from the prospective 360 RESISTANCE (360R) study, the work analyzed the evolution of clinical outcomes in 261 patients treated in 74 clinical trials conducted between 2015 and 2023 at the Cancer Molecular Therapy Research Unit UITM-CaixaResearch at VHIO, on the Vall d’Hebron Campus. Of these patients, 60% received targeted therapies selected according to the molecular profile of their tumor.

This selection is carried out at VHIO through its molecular pre-screening program, promoted by the FERO Foundation, which enables the identification of key biomarkers and the assignment of patients to the most appropriate clinical trials according to the characteristics of their tumor.

The results show a sustained increase in the objective response rate, rising from 6.4% in 2015–2016 to 25.4% in 2021–2023. In addition, more than one-third of patients achieved a clinically meaningful benefit compared with previous treatments. “These results suggest a progressive and incremental activity of specific inhibitor drugs evaluated in the course of early-phase clinical trials,” describes Dr. Alice Rossi, co-author and former oncology resident and fellow at the Cancer Molecular Therapy Research Unit.

“These findings reflect how the integration of molecular pre-screening programs and the development of more specific drugs are transforming the potential of early-phase clinical trials,” explains Dr. Alberto Hernando-Calvo, medical oncologist, researcher at UITM-CaixaResearch and senior author of the study.

The analysis also confirms that this increase in efficacy was not accompanied by an increase in severe toxicity, which remained stable over time.

The most frequent therapeutic targets included the FGFR, Ras/Raf/MAPK, SHP2 and ErbB pathways, as well as epigenetic markers.

For Dr. Elena Garralda, Director of UITM-CaixaResearch and author of the study, these findings reinforce the value of precision medicine in early clinical development: “Our results show very encouraging trends towards improved efficacy of targeted therapies in early phases, especially when treatments are assigned based on the patient’s molecular profile. This highlights the key role of molecular pre-screening programs in optimizing access to clinical trials and advancing towards a more personalized oncology.”

Reference: Rossi A, Braña I, Vieito M, Mirallas O, Navarro V, Saavedra O, Alonso Casal G, Galvao V, Lostes Bardaji MJ, Oberoi A, Pretelli G, Sanz M, Andres Bueno S, Fite Abril B, Aguilar Izquierdo S, Jimenez J, Nuciforo P, Vivancos A, Oliveira M, Baraibar I, et al.; Hernando-Calvo A. Evolving landscape of targeted therapies in early phase clinical trials. Eur J Cancer. 2026 Jun 3;240:116745. https://doi.org/10.1016/j.ejca.2026.116745