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First-in-human phase I study of EMB-02, a bispecific antibody targeting PD-1 and LAG-3 in patients with advanced
Daphne Day1, Vinod Ganju2, Ki Chung3
1Medical Oncology Department, Monash Health-Monash MedicalCentre, Clayton, VIC, Australia.
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).
Insights
This first-in-human study of EMB-02, a bispecific antibody targeting PD-1 and LAG-3, showed a favorable safety profile and early efficacy signals in advanced solid tumors. Further development is warranted based on these promising results.
Area of Science:
- Immunotherapy
- Oncology
- Clinical Trials
Background:
- EMB-02 is a novel bispecific antibody designed to simultaneously target programmed cell death protein-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3).
- This represents the first-in-human clinical evaluation of EMB-02 in patients with advanced solid tumors.
Purpose of the Study:
- To assess the safety and tolerability of EMB-02.
- To determine the maximum tolerated dose (MTD) and recommended Phase II dose(s).
- To evaluate preliminary antitumor activity, pharmacokinetic (PK) profile, and immunogenicity.
Main Methods:
- A Phase I dose-escalation study involving intravenous infusions of EMB-02 (6-900 mg) in 47 patients with advanced solid tumors.
- Safety assessments included treatment-emergent adverse events (TEAEs).
- Efficacy was evaluated by objective response rate (ORR) and clinical benefit rate at 24 weeks (CBR-24), with correlative analyses for biomarkers (PD-L1, LAG-3, MHC II).
Main Results:
- The study enrolled 47 patients; high rates of TEAEs were observed (97.9% any grade, 48.9% grade 3/4).
- The overall ORR was 6.4% and CBR-24 was 25.5%.
- Checkpoint inhibitor (CPI)-naïve patients showed a higher CBR-24 (33.3%) compared to CPI-treated patients (15%). Doses ≥360 mg achieved sustained PD-1 receptor saturation.
Conclusions:
- EMB-02 demonstrated a manageable safety profile in patients with advanced solid tumors.
- Early signs of antitumor activity were observed, particularly in CPI-naïve patients.
- These findings support the further clinical development of EMB-02.
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