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

Authors

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

Publication Date

1-1-2024

Journal

Oncoimmunology

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.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Melanoma, Carcinoma, Renal Cell, Lung Neoplasms, Antibodies, Monoclonal, Immune Checkpoint Inhibitors, Kidney Neoplasms, Biomarkers, Fatigue, Exanthema, Efficacy, ieramilimab, LAG-3 inhibitor, safety, spartalizumab Go to: Introduction

Comments

Supplementary Materials

PMID: 38170160