A Phase 1 study of BGB-B2033 (GPC3 x 4-1BB bispecific antibody) monotherapy in patients with selected advanced or metastatic solid tumors: First disclosure of clinical data

ASCO 2026 • Pan-tumor • BGB-B2033 • Rapid Oral

Hong Jae Chon, MD, PhD

DISCLAIMER

The contents of the presentations above 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 first-in-human Phase 1 study reported initial results from the monotherapy dose escalation and safety expansion of BGB-B2033, an investigational IgG-based glypican-3 (GPC3) x 4-1BB bispecific antibody, in patients with advanced or metastatic GPC3-expressing solid tumors. The primary objective was safety, with secondary objectives including preliminary antitumor activity, pharmacokinetics, and immunogenicity. As of December 10, 2025, 61 patients were enrolled, most of whom had hepatocellular carcinoma and had received a median of 2 prior lines of therapy, with a median follow-up of 3.9 months. Treatment-related treatment-emergent adverse events occurred in 44.3% of patients, with Grade ≥3 events reported in 8.2%, and one dose-limiting toxicity that resolved after dose reduction. In 59 efficacy-evaluable patients with hepatocellular carcinoma, the confirmed objective response rate was 20.3%, with 12 partial responses. Pharmacokinetic analyses showed target-mediated drug disposition at lower dose levels and decreased in a more biexponential manner at higher dose levels. Soluble 4-1BB, a pharmacodynamic marker, showed a greater increase at higher dose levels.

ClinicalTrials.gov ID: NCT06427941

Population	Intervention	Comparator	Outcome Measures
Patients with advanced or metastatic glypican-3-expressing solid tumors, who had received at least one prior systemic therapy	BGB-B2033	N/A	Safety, preliminary antitumor activity assessed by investigator-evaluated RECIST version 1.1, pharmacokinetics, and immunogenicity

FAQs

What was the objective of this study?

The objective of this study was to evaluate the safety of BGB-B2033, an investigational IgG-based glypican-3 (GPC3) x 4-1BB bispecific antibody, in patients with advanced or metastatic glypican-3-expressing solid tumors.

How was the study designed and what endpoints were assessed?

This was a first-in-human Phase 1 study consisting of a monotherapy dose-escalation and safety expansion (part A) using a Bayesian modified toxicity probability interval-2 design. Eligible patients had received at least one prior systemic therapy. The primary objective was safety. Secondary objectives included preliminary antitumor activity assessed by investigator-evaluated RECIST version 1.1, as well as pharmacokinetics and immunogenicity.

What were the primary safety and tolerability outcomes?

As of December 10, 2025, Part A enrolled 61 patients, of whom 60 (98.4%) had hepatocellular carcinoma and 56 (91.8%) were Asian. The median study follow‑up was 3.9 months (range, 0.3–14.9). Treatment‑emergent adverse events (TEAE) were reported in 63.9% of patients, and treatment‑related TEAE (TR-TEAE) occurred in 44.3%. Grade ≥3 TR-TEAEs were reported in 8.2% of patients and included increased alanine aminotransferase, increased aspartate aminotransferase, increased blood bilirubin, drug eruption, lymphopenia, and decreased neutrophil count (each 1.6%). One dose‑limiting toxicity, increased alanine aminotransferase, resolved following dose reduction. Immune‑mediated adverse events were reported in 6.6% of patients and were limited to Grade 1–2 severity. One patient reported a Grade 1 infusion-related reaction.

What were the preliminary antitumor activity findings?

Among 59 efficacy-evaluable patients with hepatocellular carcinoma, the confirmed objective response rate (ORR) was 20.3% (95% CI, 11.0-32.8), with 12 partial responses reported. Stable disease was observed in 23 patients, and progressive disease in 23 patients. Ten of the 12 responders had ongoing response at data cutoff. A preliminary dose response was observed; at doses above the predicted target efficacious dose, confirmed ORR was 28.9% (11/38).

What were the pharmacokinetic and pharmacodynamic findings?

Pharmacokinetic analyses showed target-mediated drug disposition at lower dose levels and decreased in a more biexponential manner at higher dose levels. Soluble 4-1BB, a pharmacodynamic marker, showed a greater increase at higher dose levels.

A Phase 1 study of BGB-B2033 (GPC3 x 4-1BB bispecific antibody) monotherapy in patients with selected advanced or metastatic solid tumors: First disclosure of clinical data

FAQs

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