Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
BGB-B2033 · 2 trials · 7 indications
OS is defined as the time from randomization to the date of death from any cause.
Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0/American Society for Transplantation and Cellular Therapy \[ASTCT\] for cytokine release syndrome \[CRS\] and immune effector cell-associated neurotoxicity syndrome \[ICANS\]), timing, seriousness, and relationship to study therapy; assessment of adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria
The MTD or MAD is defined as the highest dose that is tolerable or the highest dose administered, respectively.
The RP2D(s) will be determined based on a biologically effective dose by taking the totality of available preclinical and clinical data, including safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity, into consideration
ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) using Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
| Arm | Type | Description |
|---|---|---|
| BGB-B2033 | EXPERIMENTAL | Participants are randomized to receive BGB-B2033 until disease progression, unacceptable toxicity, withdrawal of consent, death, or the end of the study, whichever occurs first. |
| Investigator's choice: Lenvatinib OR sorafenib | ACTIVE_COMPARATOR | Participants are randomized to receive either lenvatinib or sorafenib, selected by the investigator before treatment, until disease progression, unacceptable toxicity, withdrawal of consent, death, or the end of the study, whichever occurs first. |
| Part A (Monotherapy Dose Escalation and Safety Expansion) | EXPERIMENTAL | Participants will receive ascending dose levels of BGB-B2033 monotherapy |
| Part B (Doublet Run-in) | EXPERIMENTAL | Participants will receive BGB-B2033 in combination with tislelizumab and to inform the starting dose of BGB-B2033 for subsequent triplet dose escalation. |
| Part B (Triplet Dose Escalation) | EXPERIMENTAL | Participants will receive BGB-B2033 in combination with tislelizumab and bevacizumab to determine the maximum tolerated dose (MTD), maximum administered dose (MAD), and recommended dose for expansion (RDFE) of the combination. |
| Part B (Triplet and Doublet Safety Expansion) | EXPERIMENTAL | Safety expansion arm for each combination therapy cohort (triplet and doublet) |
| Part C (Asia Monotherapy Dose Expansion in HCC) | EXPERIMENTAL | Participants in Asian countries with HCC will receive BGB-B2033 as monotherapy. |
| Part D (US Monotherapy Dose Expansion in HCC) | EXPERIMENTAL | Participants in the United States (US) with HCC will receive BGB-B2033 as monotherapy. |
| Part E (Monotherapy Dose Expansion in HCC) | EXPERIMENTAL | Participants with HCC will receive BGB-B2033 as monotherapy. |
| Name | Type | Description |
|---|---|---|
| BGB-B2033 | DRUG | Administered intravenously |
| Lenvatinib | DRUG | Administered by mouth as an oral capsule once daily |
| Sorafenib | DRUG | Administered by mouth as an oral tablet twice daily |
| Tislelizumab | DRUG | Administered by intravenous infusion |
| Bevacizumab | DRUG | Administered by intravenous infusion |
Key Inclusion Criteria: 1. Participants must have histologically confirmed Hepatocellular Carcinoma (HCC) that is not amenable to curative surgical or locoregional therapies. 2. Participants must have documented disease progression or intolerance after at least 1 but not exceeding 2 prior lines of ...
BGB-B2033 is being developed for hepatocellular carcinoma, including metastatic disease. It is also being studied in a Phase 1/2 trial in other GPC3-positive or AFP-producing solid tumors, such as squamous non-small cell lung cancer, gastric cancer, and extragonadal yolk sac tumors.
BGB-B2033 targets GPC3, or glypican-3, a cell surface protein. GPC3 is expressed in hepatocellular carcinoma and certain other solid tumors, which is why the program focuses on GPC3-positive cancers and includes a GPC3-positive non-small cell lung cancer cohort.
BGB-B2033 is being developed by BeOne Medicines Ltd., which trades under the ticker ONC. The company is running the clinical program for the asset, including a Phase 3 study in relapsed hepatocellular carcinoma and a Phase 1/2 study in advanced or metastatic solid tumors.
BGB-B2033 is in Phase 3 development. The Phase 3 study is not yet recruiting, while a Phase 1/2 study of BGB-B2033 alone or in combination with tislelizumab, with or without bevacizumab, is currently recruiting participants with advanced or metastatic solid tumors.
BGB-B2033 is being studied in NCT07836530, a Phase 3 trial comparing it with sorafenib or lenvatinib in relapsed hepatocellular carcinoma, and in NCT06427941, a Phase 1/2 trial in advanced or metastatic solid tumors. The Phase 3 trial is active controlled and plans to enroll 492 patients.
BGB-B2033 is investigational and has not been approved. It is still in clinical development, with a Phase 3 trial in relapsed hepatocellular carcinoma that is not yet recruiting and a Phase 1/2 trial in advanced or metastatic solid tumors that is currently recruiting participants.