Phase 1 study of BGB-B2033 (GPC3 x 4-1BB bispecific antibody) monotherapy: First disclosure of dose optimization (DO) and dose escalation (DE) update in advanced hepatocellular carcinoma (HCC)

ESMO 2026 • Hepatocellular Carcinoma • BGB-B2033 • Oral

Hong Jae Chon, MD, PhD

DISCLAIMER

The contents of the presentation are designed for educational and scientific exchange purposes and are not promotional. They may contain information on investigational products or investigational uses of approved products. No conclusions regarding safety and/or efficacy for such investigational products or uses may be made.

SUMMARY

This phase 1 study evaluated the investigational bispecific antibody BGB-B2033, which targets glypican-3 (GPC-3) and 4-1BB, in patients with advanced hepatocellular carcinoma (HCC) who had received at least one prior line of therapy. As of April 26, 2026, 110 patients were enrolled across dose-escalation (n=60) and dose-optimization (n=50) cohorts. The primary endpoints were safety and determination of the recommended phase 2 dose (RP2D). Adverse events occurred in 75% of patients and treatment-related adverse events (TRAEs) occurred in 52%; grade 3 TRAEs were reported in 5% of patients, with no grade 4 or 5 TRAEs observed. Among dose-escalation cohorts, confirmed objective response rates (ORRs) were 28.6%, 35.7%, and 20.0% at 300 mg (N=14), 600 mg (N=14), and 1000 mg (N=10), respectively; ORRs were 21.7% and 16.0% in the 450 mg (N=23) and 900 mg (N=25) dose-optimization cohorts. Among patients receiving doses ≥300 mg in dose escalation, the 6-month duration of response rate was 72.7% (95% CI, 37.1%–90.3%). The RP2D was determined to be 450 mg.

ClinicalTrials.gov ID: NCT06427941

Population Intervention Comparator Outcome Measures
Patients with advanced hepatocellular carcinoma who had received ≥1 prior line of therapy BGB-B2033 N/A
  • Primary endpoints: Safety and determination of recommended phase 2 dose
  • Key secondary endpoint: Objective response rate by investigator assessment per RECIST v1.1

FAQs

The study evaluated the investigational bispecific antibody BGB-B2033 in patients with advanced hepatocellular carcinoma who had received at least one prior line of therapy.

This was a phase 1 study of BGB-B2033 administered as monotherapy in dose-escalation (DE) and dose-optimization (DO) cohorts. Patients with advanced hepatocellular carcinoma were enrolled across doses ranging from 300 mg to 1000 mg. The primary endpoints were safety and determination of recommended phase 2 dose (RP2D), and a secondary endpoint was objective response rate (ORR) by investigator assessment according to RECIST v1.1.

As of April 26, 2026, 110 (60 DE; 50 DO) patients with HCC were enrolled. Overall, 72% of patients had ≥2 lines of therapy and 66% had prior anti–PD-(L)1 and tyrosine kinase inhibitor exposure. Median study follow-up was 6.4 months (range, 0.3–13.3) for patients receiving 300, 600, and 1000 mg, and 4.1 months (range, 0.4–5.9) for patients receiving 450 and 900 mg.

Among 110 enrolled patients, adverse events occurred in 75% and treatment-related adverse events occurred in 52%. Grade 3 treatment-related adverse events were reported in 5% of patients. No grade 4 or grade 5 treatment-related adverse events were observed.

Confirmed ORRs in the dose-escalation cohorts were 28.6% (4/14) at 300 mg, 35.7% (5/14) at 600 mg, and 20.0% (2/10) at 1000 mg. In the dose-optimization cohorts, confirmed ORRs were 21.7% (5/23) at 450 mg and 16.0% (4/25) at 900 mg. One confirmed complete response was reported in the 300 mg cohort.

RP2D was determined to be 450 mg.

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