First-in-human phase 1 dose-escalation study of W0180, an anti-VISTA monoclonal antibody, with and without pembrolizumab in patients with locally advanced or metastatic solid tumours

Gomez-Roca, C; Champiat, S; Danlos, F; Castañón Álvarez, E; Cassier, PA; Dupuy, E; Jegou, D; Primard, M; Pétain, A; Saccareau, M; Gueguen-Dorbes, G; Fabre, C; Marabelle, A; Melero, I

Journal article

First-in-human phase 1 dose-escalation study of W0180, an anti-VISTA monoclonal antibody, with and without pembrolizumab in patients with locally advanced or metastatic solid tumours

Abstract:: Objective: W0180 is a humanised IgG1κ antagonistic monoclonal antibody against the V domain-containing immunoglobulin suppressor of T-cell activation (VISTA) designed to enhance antitumour activities by inhibiting the immunosuppressive role of VISTA in myeloid cells and T cells in solid tumours. Methods and analysis: Preclinical experiments evaluated the pharmacodynamics and antitumour activity of W0180. A first-in-human phase 1 dose-escalation study investigated the maximum tolerated dose (MTD), safety/tolerability, preliminary efficacy, pharmacokinetics and pharmacodynamics of W0180, both as monotherapy and in combination with pembrolizumab (an anti-programmed cell death protein-1 (PD-1) therapy), with the aim of establishing a recommended dose for expansion (RDE). In the monotherapy arm, cohorts of patients with locally advanced/metastatic solid tumours received once-weekly W0180 at increasing doses (from 3.5 to 600 mg). In the combination therapy arm, patients with relapsed/refractory, advanced/metastatic solid tumours and ≥1 prior anti-PD (ligand)-1 therapy line received W0180 (60 or 300 mg)+pembrolizumab. Results: W0180 exhibited pH-independent blockade of the VISTA-ligand interaction in vitro and showed antitumour activity in a syngeneic preclinical murine model expressing human VISTA. In the phase 1 study, of the 33 patients in the monotherapy (n=24) or combination therapy (n=9) arms, 28 contributed to dose determination. Dose-limiting toxicities were Grade 2 cerebral infarction and Grade 3 infusion-related reaction (IRR; n=1 each). The study was terminated prematurely in the dose-escalation phase (due to a business decision by the sponsor) before the MTD/RDE was reached. Common related treatment-emergent adverse events were IRR and fatigue; most were of mild severity. No patients achieved Response Evaluation Criteria in Solid Tumours objective response; two had prolonged stable disease (SD; one from each arm). Biomarker analysis suggested a dose-dependent pharmacodynamic effect of W0180. Conclusion: W0180 demonstrated manageable safety, preliminary signs of clinical activity with prolonged SD and dose-dependent pharmacodynamics consistent with preclinical data (even though MTD was not reached) in patients with locally advanced/metastatic tumours, both as monotherapy and in combination with anti-programmed cell death protein-1 therapy. Trial registration number: NCT04564417.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Gomez-Roca, C., Champiat, S., Danlos, F., Castañón Álvarez, E., Cassier, P. A., Dupuy, E., Jegou, D., Primard, M., Pétain, A., Saccareau, M., Gueguen-Dorbes, G., Fabre, C., Marabelle, A., & Melero, I. (2026). First-in-human phase 1 dose-escalation study of W0180, an anti-VISTA monoclonal antibody, with and without pembrolizumab in patients with locally advanced or metastatic solid tumours. BMJ Oncology, 5(1).

MLA Style

Gomez-Roca, C, et al. “First-in-Human Phase 1 Dose-Escalation Study of W0180, an Anti-VISTA Monoclonal Antibody, with and without Pembrolizumab in Patients with Locally Advanced or Metastatic Solid Tumours.” BMJ Oncology, vol. 5, no. 1, 2026.

Chicago Style

Gomez-Roca, C, S Champiat, F Danlos, et al. 2026. “First-in-Human Phase 1 Dose-Escalation Study of W0180, an Anti-VISTA Monoclonal Antibody, with and without Pembrolizumab in Patients with Locally Advanced or Metastatic Solid Tumours.” BMJ Oncology 5 (1).
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