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
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 advanc...
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2290787 |
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| author | Chia-Chi Lin Elena Garralda Patrick Schöffski David S. Hong Lillian L. Siu Miguel Martin Michela Maur Rina Hui Ross A Soo Joanne Chiu Tian Zhang Brigette Ma Chrisann Kyi Daniel SW Tan Philippe A. Cassier John Sarantopoulos Andrew Weickhardt Richard D. Carvajal Jennifer Spratlin Taito Esaki Fréderic Rolland Wallace Akerley Barbara Deschler-Baier Lawrence Rispoli Tanay S. Samant Niladri Roy Chowdhury Daniel Gusenleitner Eunice L. Kwak Vasileios Askoxylakis Filippo De Braud |
| author_facet | Chia-Chi Lin Elena Garralda Patrick Schöffski David S. Hong Lillian L. Siu Miguel Martin Michela Maur Rina Hui Ross A Soo Joanne Chiu Tian Zhang Brigette Ma Chrisann Kyi Daniel SW Tan Philippe A. Cassier John Sarantopoulos Andrew Weickhardt Richard D. Carvajal Jennifer Spratlin Taito Esaki Fréderic Rolland Wallace Akerley Barbara Deschler-Baier Lawrence Rispoli Tanay S. Samant Niladri Roy Chowdhury Daniel Gusenleitner Eunice L. Kwak Vasileios Askoxylakis Filippo De Braud |
| author_sort | Chia-Chi Lin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fba32163599d40e7abcb0008f2589a1a |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-fba32163599d40e7abcb0008f2589a1a2024-12-03T13:49:35ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2023.2290787A phase 2, multicenter, open-label study of anti-LAG-3 ieramilimab in combination with anti-PD-1 spartalizumab in patients with advanced solid malignanciesChia-Chi Lin0Elena Garralda1Patrick Schöffski2David S. Hong3Lillian L. Siu4Miguel Martin5Michela Maur6Rina Hui7Ross A Soo8Joanne Chiu9Tian Zhang10Brigette Ma11Chrisann Kyi12Daniel SW Tan13Philippe A. Cassier14John Sarantopoulos15Andrew Weickhardt16Richard D. Carvajal17Jennifer Spratlin18Taito Esaki19Fréderic Rolland20Wallace Akerley21Barbara Deschler-Baier22Lawrence Rispoli23Tanay S. Samant24Niladri Roy Chowdhury25Daniel Gusenleitner26Eunice L. Kwak27Vasileios Askoxylakis28Filippo De Braud29Department of Oncology, National Taiwan University Hospital, Taipei, TaiwanVall d’Hebron Institute of Oncology (VHIO), Vall d´Hebron Hospital, Barcelona, SpainDepartment of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, BelgiumDepartment of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas and MD Anderson Cancer Center, Houston, TX, USADivision of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, CanadaGregorio Marañón Hospital, Universidad Complutense, Madrid, SpainOncology and Haematology Department, Università degli Studi di Modena e Reggio Emilia, Emilia-Romagna, ItalyDepartment of Medical Oncology, Westmead Hospital and the University of Sydney, Sydney, AustraliaDepartment of Haematology-Oncology, National University Cancer Institute, SingaporeDepartment of Medicine, Queen Mary Hospital, Hong Kong, ChinaDepartment of Medicine, Duke Cancer Institute, Durham, NC, USAPhase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USANational Cancer Centre, Singapore and Duke-NUS Medical School, SingaporeDepartment of Medical Oncology, Centre Léon Bérard, Lyon, FranceInstitute for Drug Development, Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, TX, USAMedical Oncology Dept, Olivia Newton-John Cancer Centre, Austin Health, Melbourne, Victoria, AustraliaHerbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USACross Cancer Institute, University of Alberta, Edmonton, CanadaDepartment of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, JapanDepartment of Medical Oncology, Institut de Cancérologie de l’Ouest – Centre René Gauducheau, Nantes, FranceHuntsman Cancer Institute, University of Utah, Salt Lake City, UT, USATranslational Oncology, Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, GermanyNovartis Institutes for BioMedical Research, Cambridge, MA, USANovartis Pharmaceuticals Corporation, East Hanover, NJ, USANovartis Pharmaceuticals Corporation, East Hanover, NJ, USANovartis Institutes for BioMedical Research, Cambridge, MA, USANovartis Institutes for BioMedical Research, Cambridge, MA, USANovartis Institutes for BioMedical Research, Cambridge, MA, USAMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy and Oncology and Hemato-oncology Department, University of Milan, Milan, ItalyIeramilimab, 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.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2290787EfficacyieramilimabLAG-3 inhibitorsafetyspartalizumab |
| spellingShingle | Chia-Chi Lin Elena Garralda Patrick Schöffski David S. Hong Lillian L. Siu Miguel Martin Michela Maur Rina Hui Ross A Soo Joanne Chiu Tian Zhang Brigette Ma Chrisann Kyi Daniel SW Tan Philippe A. Cassier John Sarantopoulos Andrew Weickhardt Richard D. Carvajal Jennifer Spratlin Taito Esaki Fréderic Rolland Wallace Akerley Barbara Deschler-Baier Lawrence Rispoli Tanay S. Samant Niladri Roy Chowdhury Daniel Gusenleitner Eunice L. Kwak Vasileios Askoxylakis Filippo De Braud 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 OncoImmunology Efficacy ieramilimab LAG-3 inhibitor safety spartalizumab |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | phase 2 multicenter open label study of anti lag 3 ieramilimab in combination with anti pd 1 spartalizumab in patients with advanced solid malignancies |
| topic | Efficacy ieramilimab LAG-3 inhibitor safety spartalizumab |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2290787 |
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