Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/34841
Title: A phase 2, multicenter, open-label study of anti-LAG-3 ieramilimab in combination with anti-PD-1 spartalizumab in patients with advanced solid malignancies.
Austin Authors: Lin, Chia-Chi;Garralda, Elena;Schöffski, Patrick;Hong, David S;Siu, Lillian L;Martin, Miguel;Maur, Michela;Hui, Rina;Soo, Ross A;Chiu, Joanne;Zhang, Tian;Ma, Brigette;Kyi, Chrisann;Tan, Daniel Sw;Cassier, Philippe A;Sarantopoulos, John;Weickhardt, Andrew J ;Carvajal, Richard D;Spratlin, Jennifer;Esaki, Taito;Rolland, Fréderic;Akerley, Wallace;Deschler-Baier, Barbara;Rispoli, Lawrence;Samant, Tanay S;Chowdhury, Niladri Roy;Gusenleitner, Daniel;Kwak, Eunice L;Askoxylakis, Vasileios;De Braud, Filippo
Affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Vall d'Hebron Institute of Oncology (VHIO), Vall d´Hebron Hospital, Barcelona, Spain.
Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas and MD Anderson Cancer Center, Houston, TX, USA.
Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada.
Gregorio Marañón Hospital, Universidad Complutense, Madrid, Spain.
Oncology and Haematology Department, Università degli Studi di Modena e Reggio Emilia, Emilia-Romagna, Italy.
Department of Medical Oncology, Westmead Hospital and the University of Sydney, Sydney, Australia.
Department of Haematology-Oncology, National University Cancer Institute, Singapore.
Department of Medicine, Queen Mary Hospital, Hong Kong, China.
Department of Medicine, Duke Cancer Institute, Durham, NC, USA.
Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Hong Kong, China.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
National Cancer Centre, Singapore and Duke-NUS Medical School, Singapore.
Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
Institute for Drug Development, Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, TX, USA.
Olivia Newton-John Cancer Wellness and Research Centre
Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
Cross Cancer Institute, University of Alberta, Edmonton, Canada.
Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
Department of Medical Oncology, Institut de Cancérologie de l'Ouest - Centre René Gauducheau, Nantes, France.
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Translational Oncology, Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany.
Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
Medical Oncology
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy and Oncology and Hemato-oncology Department, University of Milan, Milan, Italy.
Issue Date: 2024
Date: 2023
Publication information: Oncoimmunology 2024; 13(1)
Abstract: Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated). Patients received ieramilimab (400 mg) followed by spartalizumab (300 mg) every 3 weeks. The primary endpoint was objective response rate (ORR), along with safety, pharmacokinetics, and biomarker assessments. Of 235 patients, 142 were naive to anti-PD-1/L1 and 93 were pretreated with anti-PD-1/L1 antibodies. Durable responses (>24 months) were seen across all indications for patients naive to anti-PD-1/L1 and in melanoma and RCC patients pretreated with anti-PD1/L1. The most frequent study drug-related AEs were pruritus (15.5%), fatigue (10.6%), and rash (10.6%) in patients naive to anti-PD-1/L1 and fatigue (18.3%), rash (14.0%), and nausea (10.8%) in anti-PD-1/L1 pretreated patients. Biomarker assessment indicated higher expression of T-cell-inflamed gene signature at baseline among responding patients. Response to treatment was durable (>24 months) in some patients across all enrolled indications, and safety findings were in accordance with previous and current studies exploring LAG-3/PD-1 blockade.
URI: https://ahro.austin.org.au/austinjspui/handle/1/34841
DOI: 10.1080/2162402X.2023.2290787
ORCID: 
Journal: Oncoimmunology
Start page: 2290787
PubMed URL: 38170160
ISSN: 2162-402X
Type: Journal Article
Subjects: Efficacy
LAG-3 inhibitor
ieramilimab
safety
spartalizumab
Carcinoma, Non-Small-Cell Lung/drug therapy
Melanoma/drug therapy
Melanoma/genetics
Carcinoma, Renal Cell/drug therapy
Lung Neoplasms/drug therapy
Antibodies, Monoclonal/therapeutic use
Immune Checkpoint Inhibitors/therapeutic use
Kidney Neoplasms/drug therapy
Fatigue/chemically induced
Fatigue/drug therapy
Exanthema/chemically induced
Exanthema/drug therapy
Appears in Collections:Journal articles

Show full item record

Page view(s)

18
checked on Oct 16, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.