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 Journal Article
| Authors: | Lin, C. C.; Garralda, E.; Schöffski, P.; Hong, D. S.; Siu, L. L.; Martin, M.; Maur, M.; Hui, R.; Soo, R. A.; Chiu, J.; Zhang, T.; Ma, B.; Kyi, C.; Tan, D. S. W.; Cassier, P. A.; Sarantopoulos, J.; Weickhardt, A.; Carvajal, R. D.; Spratlin, J.; Esaki, T.; Rolland, F.; Akerley, W.; Deschler-Baier, B.; Rispoli, L.; Samant, T. S.; Chowdhury, N. R.; Gusenleitner, D.; Kwak, E. L.; Askoxylakis, V.; De Braud, F. |
| Article 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 |
| 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. © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. |
| Keywords: | immunohistochemistry; human tissue; treatment response; genetics; clinical trial; constipation; fatigue; advanced cancer; area under the curve; diarrhea; drug efficacy; drug safety; drug withdrawal; biomarkers; biological marker; melanoma; phase 2 clinical trial; gene expression; anemia; nausea; carcinoma, non-small-cell lung; lung neoplasms; renal cell carcinoma; kidney neoplasms; monoclonal antibody; abdominal pain; arthralgia; backache; coughing; dyspnea; fever; pruritus; rash; lung tumor; antibodies, monoclonal; kidney tumor; carcinoma, renal cell; multicenter study; immunogenicity; mesothelioma; safety; headache; phase 1 clinical trial; drug half life; exanthema; non small cell lung cancer; efficacy; triple negative breast cancer; appetite disorder; immune checkpoint inhibitor; humans; human; article; rna sequencing; immune checkpoint inhibitors; solid malignant neoplasm; maximum concentration; spartalizumab; ieramilimab; lag-3 inhibitor |
| Journal Title: | OncoImmunology |
| Volume: | 13 |
| Issue: | 1 |
| ISSN: | 2162-4011 |
| Publisher: | Landes Bioscience |
| Date Published: | 2024-01-01 |
| Start Page: | 2290787 |
| Language: | English |
| DOI: | 10.1080/2162402x.2023.2290787 |
| PUBMED: | 38170160 |
| PROVIDER: | scopus |
| PMCID: | PMC10761073 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
