First-in-human, phase 1, open-label study of alomfilimab, an anti-ICOS antibody, as a single agent and in combination with anti-PD-L1 in advanced malignancies.
Journal
Journal for immunotherapy of cancer
Journal Volume
14
Journal Issue
6
Start Page
e013540
ISSN
2051-1426
Date Issued
2026-06-08
Author(s)
Naing, Aung
Patel, Manish R
Curigliano, Giuseppe
Burris, Howard A
Thistlethwaite, Fiona
De Braud, Filippo
Minchom, Anna
Ascierto, Paolo A
Wake, Matthew
Nguyen, Mai A
Abbadessa, Giovanni
Sainson, Richard C A
Palu, Cintia C
Quaratino, Sonia
Deantonio, Cecilia
Abstract
Background: Immunosuppression mechanisms mediated by regulatory T cells (Tregs) can lead to poor clinical outcomes in patients undergoing immune-based therapies. Activation markers, such as inducible T-cell co-stimulator (ICOS), are highly expressed on the surface of tumor-infiltrating Tregs and present as relevant targets for targeted depletion of these cells. Here, we present clinical outcomes from a Phase 1 study (NCT03829501) of an anti-ICOS antibody of alomfilimab (SAR445256 or KY1044) as monotherapy and in combination with the anti-programmed death-ligand 1 (PD-L1) antibody, atezolizumab, in patients with advanced solid tumors.
Methods: Alomfilimab was administered intravenously once every 3 weeks (Q3W) ±3 days at six dose levels (DLs; 0.8 mg to 240 mg) as monotherapy and five DLs (0.8 mg to 80 mg) in combination with atezolizumab (1,200 mg Q3W ±3 days). Eligible patients must have had advanced metastatic disease as determined by Response Evaluation Criteria in Solid Tumors V.1.1 and no viable treatment options according to National Comprehensive Cancer Network guidelines.
Results: Overall 38 patients were enrolled in the monotherapy cohort, and 102 patients were enrolled in the combination therapy cohort. Alomfilimab had a manageable safety profile and showed a trend toward modest efficacy in tumor growth control when combined with anti-PD-L1 in selected malignancies. At least one treatment-emergent adverse event was reported in 35 patients (89.7%) in the monotherapy cohort, and in 99 (98%) patients in the combination cohort. Objective response was not observed in the monotherapy cohort. In the combination cohort, seven patients had an objective response. Median time to progression-free survival was 2 months for both cohorts. Furthermore, alomfilimab showed evidence of target engagement on T-cell subsets, specifically cluster of differentiation (CD)4+memory cells, in both single-agent and in combination treatment with atezolizumab. This was accompanied by transient elevation of granulocyte-macrophage colony-stimulating factor, interferon-γ, and tumor necrosis factor-α levels and dose-dependent reduction of ICOS+Tregs in the tumor microenvironment.
Conclusions: Alomfilimab treatment was associated with an acceptable safety profile across both mono and combination approaches, accompanied by decreased ICOS+Tregs populations and enhanced CD4+ and CD8+ effector T cells cell activity. Limited clinical activity was observed despite evidence of biological activity.
Trial registration number: NCT03829501.
Subjects
Immune Checkpoint Inhibitor
Immunosuppression
Solid tumor
T regulatory cell - Treg
Tumor microenvironment - TME
Type
journal article