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
Oncoimmunology
Journal Volume
13
Journal Issue
1
Date Issued
2024
Author(s)
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
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
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.
Subjects
Efficacy; LAG-3 inhibitor; ieramilimab; safety; spartalizumab
SDGs
Type
journal article