Study of Bcl-2 Inhibitor BGB-11417 in Participants With Mature B-Cell Malignancies

A Phase 1a/1b Open-Label Dose Escalation and Expansion Study of Bcl-2 Inhibitor BGB-11417 in Patients With Mature B-Cell Malignancies

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.

Study Overview

• Status: Recruiting
• Conditions: Mature B-Cell Malignancies
• Intervention / Treatment: Drug: BGB-11417; Drug: Zanubrutinib; Drug: obinutuzumab

• Study Type: Interventional
• Enrollment (Estimated): 537
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: 1-877-828-5568; Email: ClinicalTrials@beigene.com

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital
    • Orange, New South Wales, Australia, 2800
      • Recruiting
      • Orange Health Service (Central West Cancer Care Centre)
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Recruiting
      • Pindara Private Hospital
    • Tugun, Queensland, Australia, 4224
      • Recruiting
      • John Flynn Private Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
    • Bedford PK, South Australia, Australia, 5042
      • Recruiting
      • Flinders Medical Centre
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Recruiting
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Health
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St Vincents Hospital Melbourne
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter Maccallum Cancer Centre
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
  • Ulm, Germany, 89081
    • Recruiting
    • Universitaetsklinikum Ulm, Innere Medizin Iii
• Italy
  • Milano, Italy, 20162
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Milano, Italy, 20132
    • Recruiting
    • Ospedale San Raffaele
  • Ravenna, Italy, 48121
    • Recruiting
    • Azienda Unita Sanitaria Locale di Ravenna
  • Verona, Italy, 37134
    • Recruiting
    • Centroricerche Cliniche Di Verona Srl
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland City Hospital
  • Takapuna, New Zealand, 0622
    • Recruiting
    • North Shore Hospital
  • Wellington, New Zealand, 6021
    • Recruiting
    • Wellington Regional Hospital (Ccdhb)
• Spain
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital de La Santa Creu I Sant Pau
  • Barcelona, Spain, 8036
    • Recruiting
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08035
    • Recruiting
    • Vall d Hebron Institute of Oncology VHIO
  • Barcelona, Spain, 08907
    • Recruiting
    • Ico H Duran I Reynals
  • Madrid, Spain, 28040
    • Recruiting
    • START Madrid Fundación Jiménez Díaz
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Universidad de Navarra Pamplona
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Universitario de Salamanca
  • Santander, Spain, 39008
    • Recruiting
    • Hospital Universitario Marques de Valdecilla
• United Kingdom
  • Oxford, United Kingdom, OX42PG
    • Recruiting
    • Oxford University Hospitals NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Hematologyoncology
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Rochester
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center MSKCC
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The James Cancer Hospital and Solove Research Institute At Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • Upmc Hillman Cancer Center(Univ of Pittsburgh)
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 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 + 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	Up to 30 days after the last dose of study drug, an average of 18 months
Number of Participants Experiencing Serious Adverse Events (SAEs)	Up to 30 days after the last dose of study drug, an average of 18 months
Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of BGB-11417	Up to 30 days after the last dose of study drug, an average of 18 months
Part 1, Part 3: Maximum Tolerated Dose (MTD)	Day 1 to 21 days target dose of the study drug, an average of 18 months
Part 1, Part 3: Maximum RP2D of BGB-11417	Day 1 to last dose of study drug, an average of 18 months
Part 1, Part 3: Number of participants experiencing tumor lysis syndrome (TLS) relevant events	Up to 30 days after the last dose of study drug, an average of 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of BGB-11417		Predose up to 12 hours postdose
Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-11417		Predose up to 12 hours postdose
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of BGB-11417		Predose up to 12 hours postdose
Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of BGB-11417		Predose up to 12 hours postdose
Time to Maximum Plasma Concentration (Tmax) of BGB-11417		Predose up to 12 hours postdose
Apparent Clearance (CL/F) of BGB-11417		Predose up to 12 hours postdose
Apparent volume of distribution (Vz/F) of BGB-11417		Predose up to 12 hours postdose
Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of BGB-11417		Predose up to 12 hours postdose
Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib		Predose up to 12 hours postdose
Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-11417		Predose up to 12 hours postdose
Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib		Predose up to 12 hours postdose
Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-11417		Predose up to 12 hours postdose
Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of zanubrutinib		Predose up to 12 hours postdose
Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-11417		Predose up to 12 hours postdose
Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib		Predose up to 12 hours postdose
Part 2: AUC of BGB-11417 administered after a high fat/calorie meal (HF-Fed)		Predose up to 12 hours postdose
Part 2: Cmax of BGB-11417 administered after a high fat/calorie meal (HF-Fed)		Predose up to 12 hours postdose
Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator	ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)	Up to 30 days after the last dose of study drug, an average of 18 months

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: David Simpson, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2020
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2027

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: NHL; MCL; MZL; CLL; SLL; WM; BCL2 Inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Obinutuzumab; Zanubrutinib
• Other Study ID Numbers: BGB-11417-101; CTR20231287 (Registry Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No