Home > Research > Scientific Programmes: Clinical Research Programme > H12O-CNIO Lung Cancer Clinical Research Unit

Clinical Research Programme

H12O-CNIO Lung Cancer Clinical Research Unit

Head of Unit:  Luis Gonzaga Paz-Ares
Research highlights
Biomarker discovery and implementation

Our Group has deciphered the biological role of FGFR1 and FGFR4 in non-small cell lung cancer (NSCLC) and has developed new biomarkers with predictive roles for anti-FGFR therapy in NSCLC. The data show that the determination of FGFR1/4 gene amplification or expression alone is not sufficient to predict the efficacy of antiFGFR therapy, but that a complementary determination of a biomarker expression may further optimise patient selection for this therapeutic strategy (manuscripts and patent applications have been submitted). Currently, the Group is: validating the results on a series of well-characterised PDX models; generating an antibody against the new biomarker in order to develop a diagnostic kit; carrying out the technical validation of the biomarker; and submitting a phase II trial proposal with an FGFR inhibitor in NSCLC patients with high expression of this biomarker.

The Group has also validated an NGS-based algorithm for the determination of genomic aberrations − in tumour tissue as well as in cfDNA − that could be used to guide treatment in clinical practice.

Early clinical trials

Our Group has significantly expanded its activity of testing new molecules and combinations in solid tumours, particularly in the area of immune-based approaches, and has participated in more than 25 projects in this area of research in 2017. Recently, we provided key delivery and feasibility data supporting the use of IV infusion of enadenotucirev (or therapeutic transgenebearing derivatives of it) in clinical trials across a range of epithelial tumours, including the ongoing combination study of enadenotucirev with the checkpoint inhibitor nivolumab. This phase I study also provided insights into the potential immunestimulating properties of enadenotucirev (R Garcia-Carbonero et al., J Immunother Cancer 2017). Encouraging data on the novel combination of pembrolizumab plus ramucirumab in the cohort of non-small-cell lung cancer were updated at ASCO 2017 showing a response rate of 35 % and 9.7-months of progression-free survival in pretreated patients. Finally, data of a first-in-human trial with a novel T-cell bispecific antibody targeting carcinoembryonic antigen expressed on tumour cells and CD3 on T-cells, with or without atezolizumab, was communicated on at the ASCO annual meeting.

Changing standard-of-care treatments in clinical practice

The Lung Cancer Clinical Research Unit has led and has actively contributed to phase III trials whose results have had a significant impact on the clinical practice in the context of EGFR mutated (L Paz-Ares et al., Ann Oncol 2017), ALK translocated (Soria JC et al., NEJM 2017) or unselected (Carbone D et al., NEJM 2017) stage IV lung cancer. More recently, Luis Paz-Ares communicated, at the ESMO 2017 Congress, the results of a Phase III trial showing a profound reduction in disease progression for stage III NSCLC patients treated with the anti PD-L1 agent Durvalumab following chemoradiation.