Leonel F. Hernandez‐Aya
A5089182718- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Cancer Immunotherapy and Biomarkers
- Melanoma and MAPK Pathways
- Immunotherapy and Immune Responses
- Breast Cancer Treatment Studies
- Cancer Treatment and Pharmacology
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Ocular Oncology and Treatments
- Cancer Genomics and Diagnostics
- Nonmelanoma Skin Cancer Studies
- Cutaneous Melanoma Detection and Management
- Click Chemistry and Applications
- Lung Cancer Research Studies
- Nanoplatforms for cancer theranostics
- Cancer-related Molecular Pathways
- Lung Cancer Treatments and Mutations
- Hedgehog Signaling Pathway Studies
- Colorectal Cancer Treatments and Studies
- Quinazolinone synthesis and applications
- Adenosine and Purinergic Signaling
- BRCA gene mutations in cancer
- Multiple Myeloma Research and Treatments
- Breast Lesions and Carcinomas
Washington University in St. Louis
2016-2024
University of Miami
2011-2024
Sylvester Comprehensive Cancer Center
2011-2024
American Academy of Dermatology
2022
Melanoma Institute Australia
2021
Princess Máxima Center
2021
Royal North Shore Hospital
2021
Ospedale Papa Giovanni XXIII
2021
Princess Alexandra Hospital
2021
The Netherlands Cancer Institute
2021
The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial evaluate as adjuvant therapy in resected, high-risk stage III melanoma.Patients completely resected melanoma were randomly assigned (with stratification according cancer geographic region) receive 200 mg of (514 patients) or placebo (505 intravenously every weeks for total 18 doses (approximately...
No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because mutation burden tumor is high and disease risk strongly associated with immunosuppression. In dose-escalation portion phase 1 study cemiplimab, a deep durable response was observed in patient metastatic carcinoma.We report results cemiplimab expansion cohorts patients locally or carcinoma, as well pivotal 2 cohort...
Whether immune-related adverse events (irAEs) indicate drug activity in patients treated with immune checkpoint inhibitors remains unknown.To investigate the association between irAEs and recurrence-free survival (RFS) double-blind EORTC 1325/KEYNOTE-054 clinical trial comparing pembrolizumab therapy placebo for treatment of high-risk stage III melanoma.A total 1019 adults melanoma were randomly assigned on a 1:1 ratio to receive or placebo. Eligible 18 years older complete resection...
Abstract Adenosine mediates immunosuppression within the tumor microenvironment through triggering adenosine 2A receptors (A2AR) on immune cells. To determine whether this pathway could be targeted as an immunotherapy, we performed a phase I clinical trial with small-molecule A2AR antagonist. We find that molecule can safely block signaling in vivo. In cohort of 68 patients renal cell cancer (RCC), also observe responses alone and combination anti–PD-L1 antibody, including subjects who had...
We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage melanoma. On basis 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared placebo. This led approval adjuvant treatment by Medicines Agency US Food Drug Administration. Here, we report an updated...
Background Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in Phase 1 advanced cutaneous squamous carcinoma (CSCC) expansion cohort ( NCT02383212 ) and the pivotal 2 study NCT02760498 ). Here we report primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) provide longer-term update after weight-based mg/kg (Q2W) 1) among metastatic CSCC (mCSCC) patients Methods...
Abstract In patients with previously treated metastatic uveal melanoma, the historical 1 year overall survival rate is 37% a median of 7.8 months. We conducted multicenter, single-arm, open-label phase 2 study tebentafusp, soluble T cell receptor bispecific (gp100×CD3), in 127 treatment-refractory melanoma (NCT02570308). The primary endpoint was estimation objective response based on RECIST (Response Evaluation Criteria Solid Tumours) v1.1. Secondary objectives included safety, survival,...
Abstract Purpose: PD-1/L1 axis–directed therapies produce clinical responses in a subset of patients; therefore, biomarkers response are needed. We hypothesized that quantifying key immunosuppression mechanisms within the tumor microenvironment by multiparameter algorithms would identify strong predictors anti–PD-1 response. Experimental Design: Pretreatment biopsies from 166 patients treated with across 10 academic cancer centers were fluorescently stained multiple markers discovery (n =...
Purpose To evaluate the clinical outcomes and relationship between tumor size, lymph node status, prognosis in a large cohort of patients with confirmed triple receptor–negative breast cancer (TNBC). Patients Methods We reviewed 1,711 TNBC diagnosed 1980 2009. were categorized by size nodal status. Kaplan-Meier product limit method was used to calculate overall survival (OS) relapse-free (RFS). A Sidak adjustment for multiple group comparisons. Cox proportional hazards models fit determine...
Background To provide pooled longer term data from three groups of a phase 2 study cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), and to determine duration response (DOR) impact on quality life (QoL). Methods Patients received 3 mg/kg every weeks (group 1, metastatic CSCC [mCSCC], n=59; group 2, locally CSCC, n=78) or 350 mg 3, mCSCC, n=56). Primary endpoint was objective rate (ORR) per independent central review (ICR). QoL repeatedly measured at day 1 each...
Tumor-infiltrating myeloid cells contribute to the development of immunosuppressive tumor microenvironment. Myeloid cell expression arginase 1 (ARG1) promotes a protumor phenotype by inhibiting T function and depleting extracellular l-arginine, but mechanism underlying this expression, especially in breast cancer, is poorly understood. In cancer clinical samples our mouse models, we identified tumor-derived GM-CSF as primary regulator ARG1 local immune suppression through gene-KO screen...
PURPOSE This phase I study aimed to define the recommended II dose (RP2D) of tebentafusp, a first-in-class T-cell receptor/anti-CD3 bispecific protein, using three-week step-up dosing regimen, and assess its safety, pharmacokinetics, pharmacodynamics, preliminary clinical activity in patients with metastatic uveal melanoma (mUM). METHODS In this open-label, international, I/II study, HLA-A*02 or HLA-A*02:01+ mUM received tebentafusp 20 μg once week 1 30 2. Dose escalation (starting at 54 μg)...
Autophagy is a resistance mechanism to BRAF/MEK inhibition in BRAFV600-mutant melanoma. Here we used hydroxychloroquine (HCQ) inhibit autophagy combination with dabrafenib 150 mg twice daily and trametinib 2 every day (D+T).
Abstract Purpose: Clinical biomarkers to identify patients unlikely benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis genomic features for predicting and monitoring treatment resistance. Experimental Design: ctDNA was isolated 216 plasma samples collected 51 hormone receptor–positive (HR+)/HER2-negative (HER2−) metastatic breast cancer (MBC) on phase II trial of palbociclib...
Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors are now the standard of care for hormone receptor-positive (HR+), HER2-negative (HER-) metastatic breast cancer (MBC). However, guidelines lacking regarding their optimal sequencing with other available agents. This study examines physician practice patterns and treatment outcomes palbociclib subsequent therapies in a real-world setting. Methods: A retrospective chart review was conducted consecutive patients MBC who received between...
Combining PD-L1 blockade with inhibition of oncogenic mitogen-activated protein kinase (MAPK) signaling may result in long-lasting responses patients advanced melanoma. This phase 1, open-label, dose-escalation and -expansion study (NCT02027961) investigated safety, tolerability preliminary efficacy durvalumab (anti-PD-L1) combined dabrafenib (BRAF inhibitor) trametinib (MEK for BRAF-mutated melanoma (cohort A, n = 26), or given concomitantly B, 20) sequentially C, 22) BRAF-wild type Adverse...