{Reference Type}: Multicenter Study
{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.
{Author}: Lin CC;Garralda E;Schöffski P;Hong DS;Siu LL;Martin M;Maur M;Hui R;Soo RA;Chiu J;Zhang T;Ma B;Kyi C;Tan DS;Cassier PA;Sarantopoulos J;Weickhardt A;Carvajal RD;Spratlin J;Esaki T;Rolland F;Akerley W;Deschler-Baier B;Rispoli L;Samant TS;Chowdhury NR;Gusenleitner D;Kwak EL;Askoxylakis V;De Braud F;
{Journal}: Oncoimmunology
{Volume}: 13
{Issue}: 1
{Year}: 2024
暂无{DOI}: 10.1080/2162402X.2023.2290787
{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.