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BGB-3111

Phase 3

Waldenström's Macroglobulinemia | Small molecule | Oncology |BeOne Medicines Ltd.|Last Updated: Oct 26, 2024

Success Probability

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Trial Design

RandomizedACTIVE_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment201

FDA Designations

No designations recorded

Clinical trial landscape

BGB-3111 · 4 trials · 3 indications

Phase 3 1Phase 1 3
NCT03053440A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)Waldenström's Macroglobulinemia
COMPLETED201 Analytics
PHASE3COMPLETED
A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)
Waldenström's MacroglobulinemiaUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants Achieving Either a Complete Response (CR) or Very Good Partial Response (VGPR) Using an Adaptation of the Response Criteria Updated at the Sixth International Workshop on WM as Assessed by an Independent Review Committee (IRC)
Up to approximately 2 years and 7 months

Percentage of participants with CR, defined as normal serum immunoglobulin M (IgM) levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at baseline, or VGPR, defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values.

Part A: Incidence of treatment-emergent adverse events (safety and tolerability)
Up to 8 days

Incidence of treatment-emergent adverse events reported for zanubrutinib compared with placebo

Part B: Corrected QT interval [QTc]
Up to 2 days

Evaluate the effects of single doses of zanubrutinib on the corrected QT interval \[QTc\] using the Fridericia correction \[QTcF\]) compared with placebo

Plasma concentration of BGB-3111 and rifampin to evaluate protocol specified PK parameters
Part A: Days 1 and 10
Plasma concentration of BGB-3111 and itraconazole to evaluate protocol specified PK parameters
Part B: Days 1 and 6
Pharmacokinetic Parameter: Plasma concentration of [14C]-BGB-3111 as measured by area under concentration-time curve (AUC)
Up to 13 days
Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) of [14C]-BGB-3111
Up to 13 days
Pharmacokinetic Parameter: Time To Maximum Plasma Concentration (Tmax) of [14C]-BGB-3111
Up to 13 days
Pharmacokinetic Parameter: apparent terminal elimination rate constant (λZ) of [14C]-BGB-3111
Up to 13 days
Pharmacokinetic Parameter: Half-life Period of (T1/2) of [14C]-BGB-3111
Up to 13 days
Pharmacokinetic Parameter: apparent systemic clearance (CL/F) of [14C]-BGB-3111
Up to 13 days
Pharmacokinetic Parameter: apparent volume of distribution during the terminal phase (Vz/F) of [14C]-BGB-3111
Up to 13 days
Blood and plasma concentrations of total radioactivity: Maximum Plasma Concentration (Cmax) of [14C]-BGB-3111
Up to 13 days
Blood and plasma concentrations of total radioactivity: Time To Maximum Plasma Concentration (Tmax) of [14C]-BGB-3111
Up to 13 days
Blood and plasma concentrations of total radioactivity of [14C]-BGB-3111 as measured by area under concentration-time curve (AUC)
Up to 13 days
Blood and plasma concentrations of total radioactivity: apparent terminal elimination rate constant (λZ) of [14C]-BGB-3111
Up to 13 days
Blood and plasma concentrations of total radioactivity: Half-life Period of (T1/2) of [14C]-BGB-3111
Up to 13 days
Blood and plasma concentrations of total radioactivity: apparent systemic clearance (CL/F) of [14C]-BGB-3111
Up to 13 days
Blood and plasma concentrations of total radioactivity: apparent volume of distribution during the terminal phase (Vz/F) of [14C]-BGB-3111
Up to 13 days
Urinary recovery of total radioactivity of [14C]-BGB-3111 as assessed by the amount excreted in urine per sampling interval (Aeu)
Up to 13 days
Urinary recovery of total radioactivity of [14C]-BGB-3111 as assessed by the cumulative amount excreted in urine per sampling interval (Cum Aeu)
Up to 13 days
Urinary recovery of total radioactivity of [14C]-BGB-3111 as assessed by the percentage of drug or radioactive dose excreted in urine per sampling interval (%Feu)
Up to 13 days
Urinary recovery of total radioactivity of [14C]-BGB-3111 as assessed by the cumulative percentage of drug or radioactive dose excreted in urine (Cum %Feu)
Up to 13 days
Urinary recovery of total radioactivity as assessed by the renal clearance (CLR; for BGB-3111 only)
Up to 13 days
Fecal recovery of total radioactivity as assessed by the amount of [14C]-BGB-3111 excreted in feces per sampling interval (Aef)
Up to 13 days
Fecal recovery of total radioactivity as assessed by the cumulative amount of [14C]-BGB-3111 excreted in feces per sampling interval (Cum Aef)
Up to 13 days
Fecal recovery of total radioactivity as assessed by the percentage of radioactive dose excreted in feces per sampling interval (%Fef)
Up to 13 days
Fecal recovery of total radioactivity as assessed by the cumulative percentage of radioactive dose excreted in feces per sampling interval (Cum %Fef)
Up to 13 days
Mass balance
Up to 13 days

Urine and fecal collection for Mass Balance Evaluation

Routes of elimination of [14C]-BGB-3111
Up to 13 days

Urine and fecal collection for Metabolite Profiling/Characterization

Secondary Endpoints

Percentage of Participants Achieving Major Response Rate (MRR) as Assessed by IRC
Up to approximately 2 years and 7 months
Duration of Response (DOR) as Assessed by IRC
Up to approximately 2 years and 7 months
DOR as Assessed by IRC: Event -Free Rate
12 and 18 months from the date of randomization (up to approximately 2 years and 7 months)
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arm A : IbrutinibEXPERIMENTALParticipants with the MYD88 mutation received Ibrutinib
Arm B: ZanubrutinibACTIVE_COMPARATORParticipants with the MYD88 mutation received zanubrutinib
Part A: BGB-3111EXPERIMENTAL -
Part A: PlaceboPLACEBO_COMPARATOR -
Part B: BGB-3111, Placebo, and MoxifloxicinEXPERIMENTAL -
Arm AEXPERIMENTALApproximately 20 subjects to receive BGB-3111 and rifampin
Arm BEXPERIMENTALApproximately 20 subjects to receive BGB-3111 and itraconazole

Interventions

NameTypeDescription
BGB-3111DRUG160 mg PO BID until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
IbrutinibDRUG420 mg PO QD until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
PlaceboDRUGSubjects will receive Placebo
MoxifloxacinDRUGSubjects will receive Moxifloxicin
BGB-3111 (Arm A)DRUG320 mg BGB-3111 single oral dose
RifampinDRUG600 mg rifampin once daily
BGB-3111 (Arm B)DRUGUp to 80 mg BGB-3111 single oral dose
ItraconazoleDRUG200 mg itraconazole once daily
[14C]-BGB-3111DRUG20-mg capsule containing \~200 μCi of \[14C\]-BGB-3111,
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites58

Key Inclusion Criteria: * Clinical and definitive histologic diagnosis of WM * Measurable disease, requiring treatment * Participants with no prior therapy for WM, must be considered inappropriate candidates for treatment with a standard chemoimmunotherapy regimen * Age ≥ 18 years old * Eastern Coo...

Countries:United StatesAustraliaCzechiaFranceGermanyGreeceItalyNetherlandsPolandSpainSwedenUnited Kingdom
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Frequently asked questions about BGB-3111

What is BGB-3111 used for?

BGB-3111, also known as zanubrutinib, is an investigational small molecule being studied for Waldenström's Macroglobulinemia, a rare type of non-Hodgkin lymphoma. It has also been evaluated in healthy volunteers for pharmacokinetic studies. The drug is currently in clinical development and is not yet approved for any indication.

What does BGB-3111 target?

BGB-3111 targets Bruton's tyrosine kinase (BTK), an enzyme involved in B-cell development and signaling. By inhibiting BTK, the drug aims to disrupt the growth and survival of malignant B-cells, which is relevant in Waldenström's Macroglobulinemia. This mechanism is being investigated in clinical trials.

Who makes BGB-3111?

BGB-3111 is being developed by BeOne Medicines Ltd., a biopharmaceutical company listed on the stock exchange under the ticker symbol ONC. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with Waldenström's Macroglobulinemia and in healthy subjects.

What phase is BGB-3111 in?

BGB-3111 is in Phase 1 clinical development. While a Phase 3 trial comparing BGB-3111 to ibrutinib in Waldenström's Macroglobulinemia has been completed, the drug remains investigational and has not received FDA approval. All trials listed for BGB-3111 are completed, with no active trials currently ongoing.

What clinical trials is BGB-3111 in?

BGB-3111 has been studied in several completed clinical trials, including NCT03053440, a Phase 3 study comparing BGB-3111 to ibrutinib in 201 participants with Waldenström's Macroglobulinemia. Other trials include NCT03301181, NCT03432884, and NCT04163783, which were Phase 1 studies in healthy volunteers to assess drug interactions, cardiac effects, and metabolism.

Is BGB-3111 the same as zanubrutinib?

Yes, BGB-3111 is also known as zanubrutinib. In clinical trials, the drug is referred to by both names, with zanubrutinib being the generic name used in study titles. This alternative name is important for identifying the drug in medical literature and regulatory documents.