Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) ± anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies
BackgroundLymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for the treatment of patients with advanced/metastatic solid tum...
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| Published in | Journal for immunotherapy of cancer Vol. 10; no. 2; p. e003776 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
BMJ Publishing Group Ltd
01.02.2022
BMJ Publishing Group LTD BMJ Publishing Group |
| Series | Original research |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2051-1426 2051-1426 |
| DOI | 10.1136/jitc-2021-003776 |
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| Abstract | BackgroundLymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for the treatment of patients with advanced/metastatic solid tumors with ieramilimab ±the anti-programmed cell death-1 antibody, spartalizumab.MethodsEligible patients had advanced/metastatic solid tumors and progressed after, or were unsuitable for, standard-of-care therapy, including checkpoint inhibitors in some cases. Patients received ieramilimab ±spartalizumab across various dose-escalation schedules. The primary objective was to assess the maximum tolerated dose (MTD) or recommended phase II dose (RP2D).ResultsIn total, 255 patients were allocated to single-agent ieramilimab (n=134) and combination (n=121) treatment arms. The majority (98%) had received prior antineoplastic therapy (median, 3). Four patients experienced dose-limiting toxicities in each treatment arm across various dosing cohorts. No MTD was reached. The RP2D on a 3-week schedule was declared as 400 mg ieramilimab plus 300 mg spartalizumab and, on a 4-week schedule (once every 4 weeks; Q4W), as 800 mg ieramilimab plus 400 mg spartalizumab; tumor target (LAG-3) suppression with 600 mg ieramilimab Q4W was predicted to be similar to the Q4W, RP2D schedule. Treatment-related adverse events (TRAEs) occurred in 75 (56%) and 84 (69%) patients in the single-agent and combination arms, respectively. Most common TRAEs were fatigue, gastrointestinal, and skin disorders, and were of mild severity; seven patients experienced at least one treatment-related serious adverse event in the single-agent (5%) and combination group (5.8%). Antitumor activity was observed in the combination arm, with 3 (2%) complete responses and 10 (8%) partial responses in a mixed population of tumor types. In the combination arm, eight patients (6.6%) experienced stable disease for 6 months or longer versus six patients (4.5%) in the single-agent arm. Responding patients trended towards having higher levels of immune gene expression, including CD8 and LAG3, in tumor tissue at baseline.ConclusionsIeramilimab was well tolerated as monotherapy and in combination with spartalizumab. The toxicity profile of ieramilimab in combination with spartalizumab was comparable to that of spartalizumab alone. Modest antitumor activity was seen with combination treatment.Trial registration numberNCT02460224. |
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| AbstractList | BackgroundLymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for the treatment of patients with advanced/metastatic solid tumors with ieramilimab ±the anti-programmed cell death-1 antibody, spartalizumab.MethodsEligible patients had advanced/metastatic solid tumors and progressed after, or were unsuitable for, standard-of-care therapy, including checkpoint inhibitors in some cases. Patients received ieramilimab ±spartalizumab across various dose-escalation schedules. The primary objective was to assess the maximum tolerated dose (MTD) or recommended phase II dose (RP2D).ResultsIn total, 255 patients were allocated to single-agent ieramilimab (n=134) and combination (n=121) treatment arms. The majority (98%) had received prior antineoplastic therapy (median, 3). Four patients experienced dose-limiting toxicities in each treatment arm across various dosing cohorts. No MTD was reached. The RP2D on a 3-week schedule was declared as 400 mg ieramilimab plus 300 mg spartalizumab and, on a 4-week schedule (once every 4 weeks; Q4W), as 800 mg ieramilimab plus 400 mg spartalizumab; tumor target (LAG-3) suppression with 600 mg ieramilimab Q4W was predicted to be similar to the Q4W, RP2D schedule. Treatment-related adverse events (TRAEs) occurred in 75 (56%) and 84 (69%) patients in the single-agent and combination arms, respectively. Most common TRAEs were fatigue, gastrointestinal, and skin disorders, and were of mild severity; seven patients experienced at least one treatment-related serious adverse event in the single-agent (5%) and combination group (5.8%). Antitumor activity was observed in the combination arm, with 3 (2%) complete responses and 10 (8%) partial responses in a mixed population of tumor types. In the combination arm, eight patients (6.6%) experienced stable disease for 6 months or longer versus six patients (4.5%) in the single-agent arm. Responding patients trended towards having higher levels of immune gene expression, including CD8 and LAG3, in tumor tissue at baseline.ConclusionsIeramilimab was well tolerated as monotherapy and in combination with spartalizumab. The toxicity profile of ieramilimab in combination with spartalizumab was comparable to that of spartalizumab alone. Modest antitumor activity was seen with combination treatment.Trial registration numberNCT02460224. Background Lymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for the treatment of patients with advanced/metastatic solid tumors with ieramilimab ±the anti-programmed cell death-1 antibody, spartalizumab.Methods Eligible patients had advanced/metastatic solid tumors and progressed after, or were unsuitable for, standard-of-care therapy, including checkpoint inhibitors in some cases. Patients received ieramilimab ±spartalizumab across various dose-escalation schedules. The primary objective was to assess the maximum tolerated dose (MTD) or recommended phase II dose (RP2D).Results In total, 255 patients were allocated to single-agent ieramilimab (n=134) and combination (n=121) treatment arms. The majority (98%) had received prior antineoplastic therapy (median, 3). Four patients experienced dose-limiting toxicities in each treatment arm across various dosing cohorts. No MTD was reached. The RP2D on a 3-week schedule was declared as 400 mg ieramilimab plus 300 mg spartalizumab and, on a 4-week schedule (once every 4 weeks; Q4W), as 800 mg ieramilimab plus 400 mg spartalizumab; tumor target (LAG-3) suppression with 600 mg ieramilimab Q4W was predicted to be similar to the Q4W, RP2D schedule. Treatment-related adverse events (TRAEs) occurred in 75 (56%) and 84 (69%) patients in the single-agent and combination arms, respectively. Most common TRAEs were fatigue, gastrointestinal, and skin disorders, and were of mild severity; seven patients experienced at least one treatment-related serious adverse event in the single-agent (5%) and combination group (5.8%). Antitumor activity was observed in the combination arm, with 3 (2%) complete responses and 10 (8%) partial responses in a mixed population of tumor types. In the combination arm, eight patients (6.6%) experienced stable disease for 6 months or longer versus six patients (4.5%) in the single-agent arm. Responding patients trended towards having higher levels of immune gene expression, including CD8 and LAG3, in tumor tissue at baseline.Conclusions Ieramilimab was well tolerated as monotherapy and in combination with spartalizumab. The toxicity profile of ieramilimab in combination with spartalizumab was comparable to that of spartalizumab alone. Modest antitumor activity was seen with combination treatment.Trial registration number NCT02460224. Lymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for the treatment of patients with advanced/metastatic solid tumors with ieramilimab ±the anti-programmed cell death-1 antibody, spartalizumab. Eligible patients had advanced/metastatic solid tumors and progressed after, or were unsuitable for, standard-of-care therapy, including checkpoint inhibitors in some cases. Patients received ieramilimab ±spartalizumab across various dose-escalation schedules. The primary objective was to assess the maximum tolerated dose (MTD) or recommended phase II dose (RP2D). In total, 255 patients were allocated to single-agent ieramilimab (n=134) and combination (n=121) treatment arms. The majority (98%) had received prior antineoplastic therapy (median, 3). Four patients experienced dose-limiting toxicities in each treatment arm across various dosing cohorts. No MTD was reached. The RP2D on a 3-week schedule was declared as 400 mg ieramilimab plus 300 mg spartalizumab and, on a 4-week schedule (once every 4 weeks; Q4W), as 800 mg ieramilimab plus 400 mg spartalizumab; tumor target (LAG-3) suppression with 600 mg ieramilimab Q4W was predicted to be similar to the Q4W, RP2D schedule. Treatment-related adverse events (TRAEs) occurred in 75 (56%) and 84 (69%) patients in the single-agent and combination arms, respectively. Most common TRAEs were fatigue, gastrointestinal, and skin disorders, and were of mild severity; seven patients experienced at least one treatment-related serious adverse event in the single-agent (5%) and combination group (5.8%). Antitumor activity was observed in the combination arm, with 3 (2%) complete responses and 10 (8%) partial responses in a mixed population of tumor types. In the combination arm, eight patients (6.6%) experienced stable disease for 6 months or longer versus six patients (4.5%) in the single-agent arm. Responding patients trended towards having higher levels of immune gene expression, including and , in tumor tissue at baseline. Ieramilimab was well tolerated as monotherapy and in combination with spartalizumab. The toxicity profile of ieramilimab in combination with spartalizumab was comparable to that of spartalizumab alone. Modest antitumor activity was seen with combination treatment. NCT02460224. Lymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for the treatment of patients with advanced/metastatic solid tumors with ieramilimab ±the anti-programmed cell death-1 antibody, spartalizumab.BACKGROUNDLymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for the treatment of patients with advanced/metastatic solid tumors with ieramilimab ±the anti-programmed cell death-1 antibody, spartalizumab.Eligible patients had advanced/metastatic solid tumors and progressed after, or were unsuitable for, standard-of-care therapy, including checkpoint inhibitors in some cases. Patients received ieramilimab ±spartalizumab across various dose-escalation schedules. The primary objective was to assess the maximum tolerated dose (MTD) or recommended phase II dose (RP2D).METHODSEligible patients had advanced/metastatic solid tumors and progressed after, or were unsuitable for, standard-of-care therapy, including checkpoint inhibitors in some cases. Patients received ieramilimab ±spartalizumab across various dose-escalation schedules. The primary objective was to assess the maximum tolerated dose (MTD) or recommended phase II dose (RP2D).In total, 255 patients were allocated to single-agent ieramilimab (n=134) and combination (n=121) treatment arms. The majority (98%) had received prior antineoplastic therapy (median, 3). Four patients experienced dose-limiting toxicities in each treatment arm across various dosing cohorts. No MTD was reached. The RP2D on a 3-week schedule was declared as 400 mg ieramilimab plus 300 mg spartalizumab and, on a 4-week schedule (once every 4 weeks; Q4W), as 800 mg ieramilimab plus 400 mg spartalizumab; tumor target (LAG-3) suppression with 600 mg ieramilimab Q4W was predicted to be similar to the Q4W, RP2D schedule. Treatment-related adverse events (TRAEs) occurred in 75 (56%) and 84 (69%) patients in the single-agent and combination arms, respectively. Most common TRAEs were fatigue, gastrointestinal, and skin disorders, and were of mild severity; seven patients experienced at least one treatment-related serious adverse event in the single-agent (5%) and combination group (5.8%). Antitumor activity was observed in the combination arm, with 3 (2%) complete responses and 10 (8%) partial responses in a mixed population of tumor types. In the combination arm, eight patients (6.6%) experienced stable disease for 6 months or longer versus six patients (4.5%) in the single-agent arm. Responding patients trended towards having higher levels of immune gene expression, including CD8 and LAG3, in tumor tissue at baseline.RESULTSIn total, 255 patients were allocated to single-agent ieramilimab (n=134) and combination (n=121) treatment arms. The majority (98%) had received prior antineoplastic therapy (median, 3). Four patients experienced dose-limiting toxicities in each treatment arm across various dosing cohorts. No MTD was reached. The RP2D on a 3-week schedule was declared as 400 mg ieramilimab plus 300 mg spartalizumab and, on a 4-week schedule (once every 4 weeks; Q4W), as 800 mg ieramilimab plus 400 mg spartalizumab; tumor target (LAG-3) suppression with 600 mg ieramilimab Q4W was predicted to be similar to the Q4W, RP2D schedule. Treatment-related adverse events (TRAEs) occurred in 75 (56%) and 84 (69%) patients in the single-agent and combination arms, respectively. Most common TRAEs were fatigue, gastrointestinal, and skin disorders, and were of mild severity; seven patients experienced at least one treatment-related serious adverse event in the single-agent (5%) and combination group (5.8%). Antitumor activity was observed in the combination arm, with 3 (2%) complete responses and 10 (8%) partial responses in a mixed population of tumor types. In the combination arm, eight patients (6.6%) experienced stable disease for 6 months or longer versus six patients (4.5%) in the single-agent arm. Responding patients trended towards having higher levels of immune gene expression, including CD8 and LAG3, in tumor tissue at baseline.Ieramilimab was well tolerated as monotherapy and in combination with spartalizumab. The toxicity profile of ieramilimab in combination with spartalizumab was comparable to that of spartalizumab alone. Modest antitumor activity was seen with combination treatment.CONCLUSIONSIeramilimab was well tolerated as monotherapy and in combination with spartalizumab. The toxicity profile of ieramilimab in combination with spartalizumab was comparable to that of spartalizumab alone. Modest antitumor activity was seen with combination treatment.NCT02460224.TRIAL REGISTRATION NUMBERNCT02460224. |
| Author | Hu, Tiancen Kyi, Chrisann Kwak, Eunice L Martín, Miguel Ramesh, Radha Hong, David S Hui, Rina Gusenleitner, Daniel Zhang, Tian Esaki, Taito Carvajal, Richard D Chowdhury, Niladri Roy Weickhardt, Andrew Patel, Nidhi Prawira, Amy Schöffski, Patrick Maur, Michela Soo, Ross A Yerramilli-Rao, Padmaja Sarantopoulos, John Krauss, Jürgen Deschler-Baier, Barbara De Braud, Filippo Carion, Ana Sabatos-Peyton, Catherine A Ochoa-de-Olza, María Lau, Allen Tan, Daniel S W Akerley, Wallace Samant, Tanay S Askoxylakis, Vasileios Longmire, Tyler |
| AuthorAffiliation | 6 Institute for Drug Development , Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cancer Center , San Antonio , Texas , USA 7 Columbia University Irving Medical Center , New York , New York , USA 9 National Hospital Organization Kyushu Cancer Center , Fukuoka , Japan 13 Westmead Hospital and The University of Sydney , Sydney , New South Wales , Australia 5 Vall d'Hebron University Hospital , Barcelona , Spain 11 Huntsman Cancer Institute, University of Utah , Salt Lake City , Utah , USA 15 National University Cancer Institute , Singapore 14 University of Texas Southwestern Medical Center , Dallas , Texas , USA 20 Novartis Institutes for BioMedical Research Inc , Cambridge , Massachusetts , USA 1 Department of General Medical Oncology , Leuven Cancer Institute, University Hospitals Leuven , Leuven , Belgium 4 Hospital General Universitario Gregorio Maranon , Madrid , Spain 21 The University of Texas MD Anderson Cancer Center , Houston , Texas , USA 2 National Cancer Centre |
| AuthorAffiliation_xml | – name: 7 Columbia University Irving Medical Center , New York , New York , USA – name: 3 Duke-NUS Medical School , Singapore – name: 6 Institute for Drug Development , Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cancer Center , San Antonio , Texas , USA – name: 4 Hospital General Universitario Gregorio Maranon , Madrid , Spain – name: 10 Princess Margaret Hospital Cancer Centre , Toronto , Ontario , Canada – name: 17 Austin Health , Heidelberg , Victoria , Australia – name: 2 National Cancer Centre Singapore , Singapore – name: 13 Westmead Hospital and The University of Sydney , Sydney , New South Wales , Australia – name: 19 Universitätsklinikum Würzburg , Wurzburg , Germany – name: 11 Huntsman Cancer Institute, University of Utah , Salt Lake City , Utah , USA – name: 9 National Hospital Organization Kyushu Cancer Center , Fukuoka , Japan – name: 18 National Center for Tumor Diseases , Heidelberg , Germany – name: 20 Novartis Institutes for BioMedical Research Inc , Cambridge , Massachusetts , USA – name: 21 The University of Texas MD Anderson Cancer Center , Houston , Texas , USA – name: 8 Memorial Sloan Kettering Cancer Center , New York , New York , USA – name: 12 Fondazione IRCCS, Istituto Nazionale dei Tumori , Milan , Italy – name: 15 National University Cancer Institute , Singapore – name: 16 Oncologia Medica , AOU Policlinico di Modena , Modena , Emilia-Romagna , Italy – name: 5 Vall d'Hebron University Hospital , Barcelona , Spain – name: 1 Department of General Medical Oncology , Leuven Cancer Institute, University Hospitals Leuven , Leuven , Belgium – name: 14 University of Texas Southwestern Medical Center , Dallas , Texas , USA |
| Author_xml | – sequence: 1 givenname: Patrick surname: Schöffski fullname: Schöffski, Patrick organization: Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium – sequence: 2 givenname: Daniel S W surname: Tan fullname: Tan, Daniel S W organization: Duke-NUS Medical School, Singapore – sequence: 3 givenname: Miguel surname: Martín fullname: Martín, Miguel organization: Hospital General Universitario Gregorio Maranon, Madrid, Spain – sequence: 4 givenname: María surname: Ochoa-de-Olza fullname: Ochoa-de-Olza, María organization: Vall d'Hebron University Hospital, Barcelona, Spain – sequence: 5 givenname: John surname: Sarantopoulos fullname: Sarantopoulos, John organization: Institute for Drug Development, Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, Texas, USA – sequence: 6 givenname: Richard D surname: Carvajal fullname: Carvajal, Richard D organization: Columbia University Irving Medical Center, New York, New York, USA – sequence: 7 givenname: Chrisann surname: Kyi fullname: Kyi, Chrisann organization: Memorial Sloan Kettering Cancer Center, New York, New York, USA – sequence: 8 givenname: Taito surname: Esaki fullname: Esaki, Taito organization: National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan – sequence: 9 givenname: Amy surname: Prawira fullname: Prawira, Amy organization: Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada – sequence: 10 givenname: Wallace surname: Akerley fullname: Akerley, Wallace organization: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA – sequence: 11 givenname: Filippo surname: De Braud fullname: De Braud, Filippo organization: Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy – sequence: 12 givenname: Rina surname: Hui fullname: Hui, Rina organization: Westmead Hospital and The University of Sydney, Sydney, New South Wales, Australia – sequence: 13 givenname: Tian orcidid: 0000-0001-8914-3531 surname: Zhang fullname: Zhang, Tian organization: University of Texas Southwestern Medical Center, Dallas, Texas, USA – sequence: 14 givenname: Ross A surname: Soo fullname: Soo, Ross A organization: National University Cancer Institute, Singapore – sequence: 15 givenname: Michela surname: Maur fullname: Maur, Michela organization: Oncologia Medica, AOU Policlinico di Modena, Modena, Emilia-Romagna, Italy – sequence: 16 givenname: Andrew surname: Weickhardt fullname: Weickhardt, Andrew organization: Austin Health, Heidelberg, Victoria, Australia – sequence: 17 givenname: Jürgen surname: Krauss fullname: Krauss, Jürgen organization: National Center for Tumor Diseases, Heidelberg, Germany – sequence: 18 givenname: Barbara surname: Deschler-Baier fullname: Deschler-Baier, Barbara organization: Universitätsklinikum Würzburg, Wurzburg, Germany – sequence: 19 givenname: Allen surname: Lau fullname: Lau, Allen organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 20 givenname: Tanay S surname: Samant fullname: Samant, Tanay S organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 21 givenname: Tyler surname: Longmire fullname: Longmire, Tyler organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 22 givenname: Niladri Roy surname: Chowdhury fullname: Chowdhury, Niladri Roy organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 23 givenname: Catherine A surname: Sabatos-Peyton fullname: Sabatos-Peyton, Catherine A organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 24 givenname: Nidhi surname: Patel fullname: Patel, Nidhi organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 25 givenname: Radha surname: Ramesh fullname: Ramesh, Radha organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 26 givenname: Tiancen surname: Hu fullname: Hu, Tiancen organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 27 givenname: Ana surname: Carion fullname: Carion, Ana organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 28 givenname: Daniel surname: Gusenleitner fullname: Gusenleitner, Daniel organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 29 givenname: Padmaja surname: Yerramilli-Rao fullname: Yerramilli-Rao, Padmaja organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 30 givenname: Vasileios surname: Askoxylakis fullname: Askoxylakis, Vasileios organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 31 givenname: Eunice L surname: Kwak fullname: Kwak, Eunice L organization: Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA – sequence: 32 givenname: David S orcidid: 0000-0001-8721-1609 surname: Hong fullname: Hong, David S email: dshong@mdanderson.org organization: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35217575$$D View this record in MEDLINE/PubMed |
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| Copyright | Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. 2022 Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. 2022 |
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| Snippet | BackgroundLymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical... Lymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical... Background Lymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical... |
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| SubjectTerms | Adult Aged Aged, 80 and over Antibodies Antibodies, Monoclonal, Humanized - pharmacology Antibodies, Monoclonal, Humanized - therapeutic use Biomarkers Biopsy Cancer Clinical/Translational Cancer Immunotherapy combination Cytokines Drug dosages drug therapy Gene expression Humans Immune Checkpoint Inhibitors - pharmacology Immune Checkpoint Inhibitors - therapeutic use Immunoglobulins Immunotherapy Immunotherapy - methods Ligands Metastasis Middle Aged Neoplasms - drug therapy Patients Pharmacodynamics Proteins Signal transduction Tumors Young Adult |
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| Title | Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) ± anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies |
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