LB10. A Phase 2, Open-Label, Single-Center Study of Ad-SGE-DKK3 Gene Therapy in Combination with Nivolumab in Patients with Chemotherapy-Refractory Epithelioid Pleural Mesothelioma
University of California Los Angeles
Los Angeles, CA
United States - Contact Me
Dr. Burt is Professor and Chief of the Division of Thoracic Surgery at UCLA. Dr. Burt is a robotic surgeon, a surgeon-scientist and clinical trialist, an editor, and an innovator and entrepreneur. Dr. Burt completed his undergraduate education at New York University and then pursued his medical degree at Weill Medical College of Cornell University. He completed residencies in general surgery and thoracic surgery at the Brigham & Women’s Hospital of Harvard Medical School. He is board-certified in both Surgery and Thoracic Surgery and has advanced expertise in robotic thoracic surgery. Dr. Burt leads an NIH-funded research laboratory and has completed several investigator-initiated clinical trials of novel immunotherapeutic strategies for patients with thoracic malignancies. His contributions to the field of thoracic surgery are extended through his role as Feature Editor at the Journal of Thoracic and Cardiovascular Surgery. Dr. Burt is recipient of numerous honors and awards but at the end of the day, Dr. Burt is most passionate about elevating the outstanding care of the patients served at UCLA, personally caring for these individuals, and investigating solutions for the problems that affect them.
Baylor College of Medicine
Houston, TX
United States - Contact Me
I am an instructor with clinical and research experience in thoracic malignancies, including malignant pleural mesothelioma (MPM), lung cancer, thymic epithelial tumors, and esophageal cancer. After graduating from Seoul National University College of Medicine, I have completed an internship program and a residency program in the Department of Thoracic and Cardiovascular Surgery at Seoul National University in Korea for five years, and a clinical fellowship program in the National Cancer Center Korea for three years. In addition to clinical experience, I have experienced three years of translational research in the Department of Systems Biology at UT MD Anderson Cancer Center as a postdoctoral research fellow. A Ph.D. degree was conferred by the Molecular Oncology from the Department of Medicine at Seoul National University.
Since I joined Baylor College of Medicine as a postdoctoral fellow in 2016, I am undertaking research in the field of immune-oncology of MPM and lung cancer in Dr. Burt Lab. I am particularly enthusiastic in the field of immuno-oncology with specific experience in comprehensively integrating high dimensional single-cell time-of-flight mass cytometry (CyTOF), imaging mass cytometry (IMC), mass spectrometry, and the next generation sequencing data. My research focus is comprehensive analyses of the immunologic cellular networks within MPM and lung cancer using RNA sequencing data, CyTOF, IMC, and in vivo mouse experiments to investigate the underlying mechanism of tumorigenesis and response to treatment such as adenovirus-mediated gene transfer, new drugs with therapeutic potential and immunotherapy in MPM and lung cancer.
My overarching goals are to identify potential therapeutic targets and to develop prognostic factors for thoracic malignancy, including lung cancer and MPM, by applying “comprehensive and integrated systems immunology” approaches to improve the treatment outcome of thoracic malignancy.
Description
Methods: Patients with epithelioid MPM refractory to pemetrexed-platin-based chemotherapy were treated with CT-guided intratumoral injections of Ad-SGE-DKK3 on Days 1, 8, 22, and 50 and 480mg nivolumab intravenously every 4 weeks until disease progression (Fig.1A). The primary objective was to determine objective response rate (ORR). Secondary and exploratory objectives included safety, rate of durable clinical benefit (DCB), survival, and alteration of tumor and serum biomarkers.
Results: Sixteen patients were screened for eligibility and 12 patients were enrolled between 2019 and 2022. Nine patients (75%) completed four injections of Ad-SGE-DKK3. Three patients received at least one injection of Ad-SGE-DKK3 but discontinued treatment due to disease progression (n=2) or COVID-19 infection (n=1). Two patients (16.6%) had a partial response (PR) and five (41.7%) had stable disease (SD), as the best response within the 6-month treatment timeframe (Fig.1B-C), with a DCB (PR+SD) rate of 58.3%. At 17.8 months follow-up, median overall survival and median progression-free survival were 14.5 months and 4.5 months, respectively (Fig.1D). Grade 3 adverse events developed in 5 patients (41.7%). Imaging mass cytometry on serial tumor biopsy samples (Fig.1E-F) revealed that tumor-infiltrating CD8 T cells significantly increased after treatment (Fig.1G) and that activated and memory CD8 T cells were abundant in on-treatment tumors (Fig.1H). Immunoassays in serum showed that DCB patients had lower pre-treatment levels of IL-6 and M-CSF than patients with progressive disease and sustained lower concentrations of soluble PD-L1 and M-CSF than progressors. Soluble PD-1 was significantly decreased after treatment in both groups (Fig.1I).
Conclusions: Intratumoral administration of Ad-SGE-DKK3 combined with immune checkpoint blockade showed a favorable safety profile and promising efficacy in patients with chemotherapy-refractory epithelioid MPM.