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

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 S.W. Tan, Philippe A. Cassier, John Sarantopoulos, Andrew Weickhardt, Richard D. Carvajal, Jennifer Spratlin, Taito EsakiFréderic Rolland, Wallace Akerley, Barbara Deschler-Baier, Lawrence Rispoli, Tanay S. Samant, Niladri Roy Chowdhury, Daniel Gusenleitner, Eunice L. Kwak, Vasileios Askoxylakis, Filippo De Braud

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number2290787
JournalOncoImmunology
Volume13
Issue number1
DOIs
StatePublished - 2024
Externally publishedYes

Keywords

  • Efficacy
  • LAG-3 inhibitor
  • ieramilimab
  • safety
  • spartalizumab

ASJC Scopus subject areas

  • Oncology
  • Immunology and Allergy
  • Immunology

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