Vladimir Galvao
A5037161571- Cancer Immunotherapy and Biomarkers
- Radiopharmaceutical Chemistry and Applications
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Immunotherapy and Immune Responses
- Health Systems, Economic Evaluations, Quality of Life
- Radiomics and Machine Learning in Medical Imaging
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Cell Adhesion Molecules Research
- Colorectal Cancer Treatments and Studies
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Chromatin Remodeling and Cancer
- Biosimilars and Bioanalytical Methods
- Neutropenia and Cancer Infections
- Cancer, Stress, Anesthesia, and Immune Response
- Statistical Methods in Clinical Trials
- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Health and Medical Research Impacts
Vall d'Hebron Institute of Oncology
2020-2025
Vall d'Hebron Hospital Universitari
2020-2024
Vall d'Hebron Institut de Recerca
2024
CIBBIM-Nanomedicine
2020
In this first-in-human, Phase 1, open-label, multicenter study, we evaluated JNJ-64619178, a selective and potent PRMT5 inhibitor, in patients with advanced malignant solid tumors or non-Hodgkin lymphomas (NHL). The primary objective was to evaluate the safety identify recommended 2 dose (RP2D) of JNJ-64619178.Adult treatment-refractory NHL measurable disease received escalating doses JNJ-64619178 following two schedules (Schedule A: 14 days on/7 off; Schedule B: every day on 21-day cycle)....
Nanrilkefusp alfa (nanril; SOT101) is an interleukin (IL)-15 receptor βγ superagonist that stimulates natural killer (NK) and CD8+ T cells, thereby promoting innate adaptive anti-tumor inflammatory microenvironment in mouse tumor models either monotherapy or combined with anti-programmed cell death protein 1 (PD-1) antibody. In cynomolgus monkeys, a clinical schedule was identified, which translated into the design of phase 1/1b trial, AURELIO-03 (NCT04234113). 51 patients...
Abstract Purpose: Therapeutic depletion of immunosuppressive regulatory T cells (Tregs) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and anti-tumor efficacy selective Treg by administered as monotherapy or combination with atezolizumab was evaluated two Phase I studies. Materials Methods: Adult patients...
<p><b>A,</b> Simulation plots: The PK/PD model was used to simulate both RG6292 and FOXP3<sup>+</sup> Treg levels following a range of doses. simulations were based on the population parameters from summarized (median) by analyte (green, non-Tregs; orange, Tregs) dose. solid lines represent median, shaded areas span 5th 95th percentiles, horizontal dashed 50% (red), 75% (magenta), 90% (blue) change baseline. <b>B,</b> Therapeutic window plot:...
<p>Representativeness of Study Participants.</p>
<p>Figure S1A. Study design - 1 (WP41188; NCT04158583). Figure S1B. 2 (BP42595; NCT04642365).</p>
<p>Figure S3. Spider plots showing percentage change from baseline in sum of diameters target lesions for efficacy-evaluable patients. (A) Study 1 (doses 18 mg and above) (B) 2 20 above).</p>
<p>Summary of key outcome parameters study 1 (WP41188; RG6292 every 3 weeks)</p>
<p>Figure S4. (A) The levels of peripheral CD8 T cells (CD45+CD3+CD8+) after treatment with RG6292 or (B) RG62962 in combination atezolizumab show less than 2-fold mean change absolute T-cell numbers intra patient variations (odds ratio CD8+ are calculated regards to CD3+ cells). (C) Quantitative analysis on-treatments biopsies matched baseline shows no systematic cells.</p>
<p>Safety summary</p>
<p>Summary of key outcome parameters study 2 (BP42595; RG6292 plus atezolizumab 1,200 mg every 3 weeks)</p>
<p>Patient disposition</p>
<p><b>A,</b> A single infusion of RG6292 results in sustained peripheral Treg depletion a dose-dependent manner and independent atezolizumab administration. <b>B,</b> leads to intratumoral reduction. The size the dots reflects number Tregs/mm<sup>2</sup> at baseline. Note that one sample cohort 7 (70 mg) had <1 Treg/mm<sup>2</sup> <b>C,</b> Change Teff/Treg ratio. Graphs show fold change from baseline ratio...
<p>Figure S2. Population PK/PD modeling approach: The model was used to simulate both RG6292 and FOXP3+ Treg levels, following a range of doses. which best describes the data is where previously defined drug levels (from PK model) stimulate loss CD25+ cells from plasma, in Michaelis-Menten manner. concentrations RG6282 cell count respective T were modeled simultaneous Proportional error for PD. utilized measured plasma different types, like or CD4+CD25+ IV infusion administration...
<div>AbstractPurpose:<p>Therapeutic depletion of immunosuppressive regulatory T cells (Treg) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector T-cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and antitumor efficacy selective Treg by administered as monotherapy or combination with atezolizumab were evaluated two phase I studies.</p>Patients...
Abstract Bromodomain and extraterminal proteins (BET) play key roles in regulation of gene expression, may a role cancer-cell proliferation, survival, oncogenic progression. CC-90010-ST-001 (NCT03220347) is an open-label phase I study trotabresib, oral BET inhibitor, heavily pretreated patients with advanced solid tumors relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Primary endpoints were the safety, tolerability, maximum tolerated dose, RP2D trotabresib. Secondary clinical...
3024 Background: The receptor ITGB6 plays a role in tumor pathogenesis and invasiveness, its overexpression is correlated with poor outcomes. Non-small cell lung cancer (NSCLC), head neck (HNSCC), esophageal (EC) are among tumors high expression (Lyon 2021). SGN-B6A an ITGB6-directed vedotin ADC monomethyl auristatin E (MMAE) payload. elicits antitumor activity via MMAE-mediated cytotoxicity, bystander effect, immunogenic death. Here, we present updated results of ongoing phase 1 study focus...
2502 Background: SOT101 (previously SO-C101) is a fusion protein of IL-15 and the receptor α sushi+ domain. Synergistic effects an anti-programmed cell death 1 antibody have been validated in various tumor mouse models inducing protective memory response. Methods: In this phase study, safety, tolerability, pharmacokinetics, pharmacodynamics, preliminary efficacy increasing doses administered subcutaneously were investigated patients (pts) with advanced solid tumors as monotherapy (Part A)...
8521 Background: Integrin beta-6 (IB6), a tumor-associated membrane protein, plays an important role in pathogenesis and invasiveness its expression correlates with poor outcomes. Sigvotatug vedotin (SV), formerly called SGN-B6A, is IB6-directed ADC encouraging activity NSCLC the Ph 1 study SGNB6A-001 (NCT04389632) (Hollebecque 2023). Here, we report updated efficacy safety of SV NSCLC. Methods: open-label, multicenter, evaluating safety, pharmacokinetics (PK), antitumor (cORR, DOR, PFS per...
The redirection of T lymphocytes against tumor-associated or tumor-specific antigens, using bispecific antibodies chimeric antigen receptors (CAR), has shown therapeutic success certain hematological malignancies. However, this strategy not been effective solid tumors. Here, we describe the development CAR cells targeting p95HER2, a found in HER2-amplified These display robust activity p95HER2-expressing cell lines but demonstrate limited efficacy patient-derived xenografts. As p95HER2 is...
TPS3144 Background: The extracellular matrix (ECM) plays an important role in solid tumor pathogenesis and is a major focus of research therapeutic targeting. Integrin beta-6 cell surface receptor that interacts with the ECM to mediate cellular adhesion. overexpressed numerous tumors its expression negative prognostic marker cancers including colorectal, non-small lung, gastric, cervical cancers. SGN-B6A investigational vedotin, antibody-drug conjugate directed against integrin selectively...
<h3>Background</h3> PD1-Fc-OX40L, is a hexameric, bi-functional fusion protein with an extracellular domain (ECD) of PD-1 (70 pM affinity to PD-L1) linked the ECD OX40L (324 OX40) through Fc linker. The therapeutic activity mPD1-Fc-OX40L in murine tumors was superior PD1 blocking, OX40 agonist or combination antibody therapy.<sup>1</sup> <h3>Methods</h3> first-in-human, Phase 1 dose escalation study evaluating SL-279252 as monotherapy patients (pts) advanced solid lymphomas. Objectives...
<h3>Background</h3> Integrin beta-6 plays a role in tumor pathogenesis and invasiveness, is correlated with poor outcomes several cancers, making it therapeutic target of interest.<sup>1,2</sup> SGN-B6A an investigational vedotin ADC comprised integrin beta-6-directed monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via protease-cleavable linker. elicits antitumor activity through MMAE-mediated cytotoxicity, bystander effect, immunogenic cell death.<sup>3</sup> Herein, we...