First-in-human phase I study of EMB-02, a bispecific antibody targeting PD-1 and LAG-3 in patients with advanced solid tumors
Mené sur 47 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I détermine la dose maximale tolérée de EMB-02, un anticorps bispécifique ciblant PD-1 et LAG-3, puis analyse ses caractéristiques pharmacocinétiques et son efficacité du point de vue du taux de réponse objective en semaine 24
Background: EMB-02 is a symmetric bispecific antibody targeting programmed cell death protein-1 and lymphocyte-activation gene 3 simultaneously. Here, we present the first-in-human study results of EMB-02 in patients with advanced solid tumors.
Methods: Patients were treated with intravenous infusions of EMB-02 at doses of 6–900 mg. The primary objective was to evaluate the safety and tolerability and to determine the maximum tolerated dose and/or recommended phase II dose(s). Secondary objectives included characterizing the pharmacokinetic (PK) profile, assessing preliminary antitumor activity and the immunogenicity.
Results: A total of 47 patients were enrolled. All grade and grade 3/4 treatment-emergent and treatment related adverse events occurred in 97.9%, 48.9%, 68.1% and 12.8% patients, respectively. The objective response rate (ORR) was 6.4% and clinical benefit rate at 24 weeks (CBR-24) was 25.5% in overall population. The CBR-24 was 33.3% in checkpoint inhibitor (CPI)-naïve patients, and 15% in CPI-treated. No clear relationship was observed between the efficacy and PD-L1, LAG-3, or MHC II expression level. Doses 360 mg or higher resulted in sustained saturation of PD-1 receptors on circulating CD3 + T cells.
Conclusions: EMB-02 demonstrated a favorable safety profile and early efficacy signals in multiple solid tumors, warranting further development. (NCT04618393).
British Journal of Cancer , article en libre accès 2025