Study to Evaluate the Efficacy and Safety of Sonrotoclax in Participants With Waldenström's Macroglobulinemia

PHASE2RECRUITING

This study will evaluate the safety and efficacy of the BCL2 inhibitor BGB-11417 (sonrotoclax) in participants with relapsed/refractory Waldenström's Macroglobulinemia (R/R WM) and in combination with zanubrutinib in adult participants with previously untreated WM.

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Study details:

This study will test whether BGB-11417 (sonrotoclax) can be used to improve outcomes in participants with Waldenström's Macroglobulinemia (WM) both when used alone in those who have not responded well to conventional treatments and when used in combination with zanubrutinib in those who have not yet received treatment. The main goals of the study are to determine how many participants may no longer have evidence of cancer or have some improvement in the signs and symptoms of cancer after treatment, and to determine what adverse events, or side effects, participants might experience. BCL2 is a key protein involved in cell death, and abnormal levels of BCL2 are associated with many cancers.

Blocking the action of BCL2 proteins is a promising approach with potential therapeutic benefits in participants with different types of cancers, including WM. This study will enroll approximately 105 participants. All participants will receive sonrotoclax orally as a tablet.

The study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 5 years. Treatments will continue until participants experience worsening disease status, too many side effects, or withdraw consent.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Clinical and definitive histologic diagnosis of WM.
  • Meeting ≥ 1 criterion for treatment according to consensus panel criteria from the 2nd International Workshop on Waldenström's Macroglobulinemia (IWWM).
  • For Cohorts 1-3, refractory or relapsed disease to the most recent therapy at study entry unless participants had intolerance to the most recent therapy. Refractory disease is defined as not attaining at least a major response, or progressing while on or within 6 months of completing therapy. Relapsed disease is defined as attaining at least a major response to therapy and meeting the criteria for disease progression beyond 6 months after completing therapy.
  • For Cohort 4, patients must not have received prior therapy for WM.
  • Adequate organ function.
  • Exclusion criteria

  • Central nervous system (CNS) involvement by WM.
  • Transformation to aggressive lymphoma, such as diffuse large B-cell lymphoma.
  • History of other malignancies ≤ 2 years before study entry.
  • Uncontrolled active systemic infection or recent infection requiring parenteral antimicrobial therapy that was completed ≤ 14 days before the first dose of the study drug.
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    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2023-09-28

    Primary completion: 2027-11-01

    Study completion finish: 2028-09-01

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE2

    trial

    Trial ID

    NCT05952037

    Intervention or treatment

    DRUG: BGB-11417

    DRUG: Zanubrutinib

    Conditions

    • Waldenstrom Macroglobulinemia
    • Waldenstrom's Macroglobulinemia Recurrent
    • Waldenstrom's Macroglobulinemia Refractory
    Image related to Waldenstrom Macroglobulinemia
    • Condition: Waldenstrom Macroglobulinemia, Waldenstrom's Macroglobulinemia Recurrent and more

    • DRUG: BGB-11417 and other drugs

    • Concord, New South Wales, Australia and more

    • Sponsor: BeiGene

    Find a site

    Closest Location:

    Concord Repatriation General Hospital

    Research sites nearby

    Select from list below to view details:

    • Concord Repatriation General Hospital

      Concord, New South Wales, Australia

    • Monash Health

      Clayton, Victoria, Australia

    • Flinders Medical Centre

      Bedford PK, South Australia, Australia

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    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: Cohort 1
    • Participants with R/R disease to both Bruton tyrosine kinase (BTK) inhibitor and anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor will receive sonrotoclax at a standard dose, given orally once daily.
    DRUG: BGB-11417
    • Administered orally as a tablet.
    EXPERIMENTAL: Cohort 2
    • Participants with R/R disease to anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor and were intolerant to BTK inhibitor will receive sonrotoclax at a standard dose, given orally once daily.
    DRUG: BGB-11417
    • Administered orally as a tablet.
    EXPERIMENTAL: Cohort 3
    • Participants with R/R disease to a BTK inhibitor treatment and are unsuitable for chemoimmunotherapy will receive sonrotoclax at a standard dose, given orally once daily.
    DRUG: BGB-11417
    • Administered orally as a tablet.
    EXPERIMENTAL: Cohort 4
    • Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy with fixed duration.
    DRUG: BGB-11417
    • Administered orally as a tablet.

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Cohort 1: Major Response Rate (MRR)MRR is defined as the proportion of participants achieving partial response (PR) or better, as assessed by the Independent Review Committee (IRC) per the 11th International Workshop on Waldenström Macroglobulinemia (IWWM-11) WM response criteria.Up to approximately 4 years

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Cohorts 2 and 3: MRR as assessed by the IRCMRR is defined as the proportion of participants achieving PR or better.Up to approximately 5 years
    All Cohorts: MRR as assessed by the InvestigatorMRR is defined as the proportion of participants achieving PR or better.Up to approximately 5 years
    Cohorts 1, 2, and 3: Duration of Major Response (DoMR) as assessed by the IRCDoMR is defined as the time from first determination of major response until first documentation of progression or death, whichever occurs first.Up to approximately 5 years
    All Cohorts: DoMR as assessed by the InvestigatorDoMR is defined as the time from first determination of major response until first documentation of progression or death, whichever occurs first.Up to approximately 5 years
    Cohorts 1, 2, and 3: Complete Response (CR) + Very Good Partial Response (VGPR) as assessed by the IRCCR + VGPR is defined as the percentage of participants who achieve CR or VGPR.Up to approximately 5 years
    All Cohorts: CR + VGPR as assessed by the InvestigatorCR + VGPR is defined as the percentage of participants who achieve CR or VGPR.Up to approximately 5 years
    Cohorts 1, 2, and 3: Overall Response Rate (ORR) as assessed by the IRCORR is defined as the percentage of participants with minor response (MR) or better.Up to approximately 5 years
    All cohorts: ORR as assessed by the investigatorORR is defined as the percentage of participants with MR or better.Up to approximately 5 years
    Cohorts 1, 2, and 3: Duration of Response (DOR) as assessed by the IRCDOR is defined as the time from first determination of response until first documentation of progression or death, whichever occurs first.Up to approximately 5 years
    All Cohorts: DOR as assessed by the investigatorDOR is defined as the time from first determination of response until first documentation of progression or death, whichever occurs first.Up to approximately 5 years
    Cohorts 1, 2, and 3: Progression-Free Survival (PFS)PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the IRC and by the investigator.Up to approximately 5 years
    Cohorts 1, 2, and 3: Time to major response as assessed by the IRCTime to major response is defined as the time from start of study treatment to the first documentation of major response.Up to approximately 5 years
    All Cohorts: Time to major response as assessed by the investigatorTime to major response is defined as the time from start of study treatment to the first documentation of major response.Up to approximately 5 years
    Cohorts 1, 2, and 3: Overall Survival (OS)OS is defined as the time from first study drug administration to the date of death due to any cause.Up to approximately 5 years
    Time to next treatment in cohort 4Defined as the time from the start of treatment to the start of first subsequent therapy for WM.Up to approximately 5 years
    Number of participants reporting adverse eventsNumber of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory abnormalities, physical examination results, and vital signs.Up to approximately 5 years
    Health-Related Quality of Life (HRQoL): NFLymSI-18HRQoL based on participant-reported outcomes using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 Item (NFLymSI-18) Version 4. The questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and is divided into a total score.Up to approximately 5 years

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    References

    Clinical Trials Gov: Study to Evaluate the Efficacy and Safety of Sonrotoclax in Participants With Waldenström's Macroglobulinemia

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