A. Our clinical research program is focused on the development of innovative therapies against cancer.
Several of our research trials have translated in the therapeutic current standards for clinical use. For example, the phase III clinical trials in which we have participated have contributed to the approval of Pertuzumab, currently the neoadjuvant standard of therapy in HER2+ breast cancer (ClinicalTrials.gov Identifier: NCT02132949. A Study Evaluating Pertuzumab (Perjeta) Combined With Trastuzumab (Herceptin) and Standard Anthracycline-based Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced, Inflammatory, or Early-stage Breast Cancer), the very recent approval of the the fixed-dose subcutaneous combination of trastuzumab and pertuzumab in HER2+ breast cancer (ClinicalTrials.gov Identifier: NCT03493854; A Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Participants With HER2-Positive Early Breast Cancer (FeDeriCa)), or the imminent approval of Abemaciclib in the adjuvant therapy of hormone-receptor positive early breast cancer (ClinicalTrials.gov Identifier: NCT03155997; Endocrine Therapy With or Without Abemaciclib (LY2835219) Following Surgery in Participants With Breast Cancer (monarchE)).
Testing DNA repair in advanced prostate cancer (ClinicalTrials.gov Identifier: NCT03395197; TALAPRO-2: A phase 3, randomized, double-blind, placebo-controlled study of Talazoparib with Enzalutamide in metastatic castration-resistant prostate cancer).
The approval of Durvalumab as consolidation therapy after chemotherapy and radiotherapy in unresectable stage III NSCLC, the current treatment standard (ClinicalTrials.gov Identifier: NCT02125461; A Global Study to Assess the Effects of MEDI4736 (Durvalumab) Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC)).
The approval of the combination of Dabrafenib plus Trametinib in non-small lung cancer patients with BRAF V600E mutation (ClinicalTrials.gov Identifier: NCT01336634; Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer).
Searching for new combinations of agents for the treatment of EGFR mutated lung cancer patients, specific target-therapy with crizotinib in ROS1-positive non-small cel lung cancer patients, Ganetespib in combination with docetaxel as second-line treatment, entrectinib in patients with tumors that harbor an NTRK1/2/3, ROS1, or ALK gene fusion Immunotherapy after complete surgery resection in lung cancer, immunotherapy as neoadjuvant therapy in resectable locally advanced non-small cell lung cancer, canakinumab as adjuvant treatment after surgical resection in non-small cell lung cancer patients , atezolizumab plus an antiangiogenic agent (bevacizumab) in non-squamous non-small cell patients patients with high-intermediate tumor mutation burden or Tipifarnib in squamous non-small cell lung cancer patients with HRAS mutations
We have also evaluated in phase I and phase II clinical trials novel drugs such as Nintedanib (ClinicalTrials.gov Identifier: NCT01484080; Neoadjuvant Paclitaxel versus BIBF 1120 Priming Followed by BIBF 1120 Plus Paclitaxel in Early HER-2 Negative Breast Cancer With Proteomic and Dynamic Imaging Correlates; and ClinicalTrials.gov Identifier: NCT02619162; Nintedanib+Letrozole in Postmenopausal Women with Breast Cancer: Clinical Trial Safety and Pharmacodynamics), or Dovitinib (ClinicalTrials.gov Identifier: NCT01548924; Determination of Dose of Antiangiogenic Multitargeted DOVITINIB (TKI258) Plus Paclitaxel in Patients With Solid Tumors), and monoclonal antibodies such as Durvalumab (ClinicalTrials.gov Identifier: NCT02802098; Abrogation of Chronic Monoclonal Antibody Treatment-induced T-cell Exhaustion With DURVALUMAB in Advanced HER-2 Negative Breast Cancer), and Niraparib (ClinicalTrials.gov Identifier: NCT03431350; A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer: QUEST)
B. Our translational research program is focused on the discovery of biomarkers for assessing the effects of anticancer immunotherapy and biomarkers of cancer
This includes
1. Leading national biomarkers platforms to coordinate the identification and development of biomarkers in cancer (PIE15/00068: Discovery, Validation and Implementation of Biomarkers for Precision Oncology). This platform is integrated currently by 5 research institutes linked to universitary hospitals (H. Doce de Octubre, H. Ramón y Cajal, H. Valdecilla, IRB Lleida, H. La Princesa) and 2 collaborating centres(Hospital Vall D´Hebron,Instituto de Biomedicina de Sevilla). Our centre is the responsible to analyze immune profiles in blood from cáncer patients and to caracterize cáncer associated exosomes as modulators of immune response.
2. Studying the immunophenotype profile in patients with advanced cancer through national competitive multi-centre studies: PI17/00801 Immune biomarkers response in castration resistant prostate cancer patients. Project in collaboration with CNIO, including more than 900 patients.
3. Participating in international registries for biomarkers: IRONMAN: An International Registry to Improve Outcomes in Men With Advanced Prostate Cancer (ClinicalTrials.gov Identifier: NCT03151629)
3. Looking for promising targets for new cancer treatments as: the rare double amplification of FGFR-1 and CCDN1 in breast cancer (REF study). By using a systems biology approach, we are clustering breast cancer into subtypes defined by biologic features that constitute therapeutic targets, or FGFR aberrations in urothelial cancer (ANNAR: A Study to Identify Participants With Urothelial Cancer and Fibroblast Growth Factor Receptor Gene Aberrations, ClinicalTrials.gov Identifier: NCT03955913)
4. Searching for prevention biomarkers to stop cancer development: PI14/00726 A metabolic strategy to prevent breast cancer. This project study FASN fatty acid synthase by RNA to explore the malignant transformation in breast cancer.
5. EstablIshing the utility of liquid biopsy in lung cancer patients with actionable genetic alterations (EGFR, ALK and ROS1): Clinical utility of plasma-based digital next-generation sequencing in patients with advance-stage lung adenocarcinomas with insufficient tumor samples for tissue genotyping. Zugazagoitia J, Ramos I, Trigo JM, Palka M, Gómez-Rueda A, Jantus-Lewintre E, Camps C, Isla D, Iranzo P, Ponce-Aix S, García-Campelo R, Provencio M, Franco F, Bernabé R, Juan-Vidal O, Felip E, de Castro J, Sanchez-Torres JM, Faul I, Lanman RB, Garrido P, Paz-Ares L. Ann Oncol 2019;30(2):290-296. doi: 10.1093/annonc/mdy512, and Estudio de la dinámica mutacional en pacientes de cáncer de pulmón no microcítico avanzado con mutación en EGFR en primera línea de tratamiento. Promotor: Fundación Investigación Biomedica Hospital Universitario Puerta de Hierro (FIBPH).
