Purpose

The purpose of this study is to determine the safety, tolerability; and to define the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D); and to evaluate the safety and tolerability of the ramp-up dosing schedule and at the RP2D of BGB-11417 monotherapy, and when given in combination with zanubrutinib and obinutuzumab.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Confirmed diagnosis of one of the following: NHL Cohorts: 1. MZL i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least one prior therapy ii. Active disease requiring treatment 2. FL i. R/R FL (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy 3. DLBCL i. R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed after, or was refractory to, at least two prior systemic therapies and has either progressed following or is not a candidate for autologous stem cell transplant (due to comorbidities or non-responsiveness to salvage chemotherapy) 4. Transformed indolent B-cell NHL i. Any lymphoma otherwise eligible for Part 1 that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter's transformation) are not eligible for Part 1 CLL/SLL Cohorts: 5. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria i. Disease characterized as Treatment Naive (TN) or R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy ii. Requiring treatment as defined by history MCL cohorts: 6. WHO-defined MCL I. R/R MCL defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy; ii. Requiring treatment in the opinion of the investigatorr WM cohorts: g. WHO-defined WM (clinical and definitive histologic diagnosis) i. R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy; ii. Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenström's Macroglobulinemia (Dimopoulos et al 2014) - Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI), defined as: 1. CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes measured by flow cytometry 2. DLBCL, FL, MZL, SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in at least 2 perpendicular dimensions. For MZL, isolated splenomegaly is considered measurable for this study - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 - Adequate organ function - Adequate pancreatic function indicated by: 1. Serum amylase ≤ 1.5 x upper limit of normal (ULN) 2. Serum lipase ≤ 1.5 x ULN

Exclusion Criteria

  • Known central nervous system involvement by lymphoma/leukemia - Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome - Prior therapy ≥ 2 months with or progression on a B-cell lymphoma-2 (Bcl-2) inhibitor NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
BGB-11417 Monotherapy Dose Finding: Part 1
Participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL, mantle cell lymphoma (MCL); Waldenströms macroglobulinemia (WM); and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive oral BGB-11417 until the maximum tolerated dose (MTD) (or maximum ascending dose (MAD)) and recommended phase 2 dose can be determined
  • Drug: BGB-11417
    Film-coated tablets administered once daily at a dose as specified in the treatment arm
    Other names:
    • Sonrotoclax
Experimental
BGB-11417 Monotherapy Expansion Cohorts: Part 2
Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 at the RP2D dose to further define the safety profile
  • Drug: BGB-11417
    Film-coated tablets administered once daily at a dose as specified in the treatment arm
    Other names:
    • Sonrotoclax
Experimental
BGB-11417 + Zanubrutinib Combination Therapy Dose Finding: Part 3
Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral BGB-11417 until RP2D can be determined in combination with zanubrutinib
  • Drug: BGB-11417
    Film-coated tablets administered once daily at a dose as specified in the treatment arm
    Other names:
    • Sonrotoclax
  • Drug: Zanubrutinib
    320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)
    Other names:
    • BGB-3111
Experimental
BGB-11417 + Zanubrutinib Combination Therapy Dose Expansion: Part 4
Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral BGB-11417 at an RP2D dose to further define the safety profile in combination with zanubrutinib
  • Drug: BGB-11417
    Film-coated tablets administered once daily at a dose as specified in the treatment arm
    Other names:
    • Sonrotoclax
  • Drug: Zanubrutinib
    320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)
    Other names:
    • BGB-3111
Experimental
: BGB-11417 + Zanubrutinib Combination Therapy Dose Escalation: Part 5
Participants with treatment naïve CLL/SLL will receive oral BGB-11417 until RP2D can be determined in combination with obinutuzumab without and with zanubrutinib.
  • Drug: BGB-11417
    Film-coated tablets administered once daily at a dose as specified in the treatment arm
    Other names:
    • Sonrotoclax
  • Drug: Zanubrutinib
    320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)
    Other names:
    • BGB-3111
Experimental
BGB-11417 + Zanubrutinib Combination Therapy Dose Expansion: Part 6
Participants with treatment naïve CLL/SLL will receive oral BGB-11417 at an RP2D dose to further define the safety profile in combination with obinutuzumab without and with zanubrutinib
  • Drug: BGB-11417
    Film-coated tablets administered once daily at a dose as specified in the treatment arm
    Other names:
    • Sonrotoclax
  • Drug: Zanubrutinib
    320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)
    Other names:
    • BGB-3111
  • Drug: obinutuzumab
    Given as an intravenous infusion administered per label.

Recruiting Locations

University of Kansas Medical Center Research Institute
Kansas City, Kansas 66160

More Details

Status
Recruiting
Sponsor
BeiGene

Study Contact

BeiGene
1-877-828-5568
clinicaltrials@beigene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.