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Study of BGB-11417 in Adult Participants With Mature B-cell Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04883957
Recruitment Status : Recruiting
First Posted : May 12, 2021
Last Update Posted : June 1, 2023
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
The purpose of this study is to evaluate the safety and tolerability of BGB-11417 monotherapy, define the maximum tolerated dose (MTD) or maximum administered dose and the recommended Phase 2 dose (RP2D) of BGB-11417 monotherapy for the selected B-cell malignancy dose finding cohorts, and evaluate the safety and tolerability of the ramp-up dosing schedule in the evaluated disease types.

Condition or disease Intervention/treatment Phase
Mature B-cell Malignancies Drug: BGB-11417 Phase 1

Detailed Description:
This study will have 3 cohorts for determining a monotherapy MTD and ramp-up schedule: Cohort A, participants with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R NHL); Cohort B, participants with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with low tumor burden; Cohort C, participants with R/R CLL/SLL with high tumor burden.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Bcl-2 Inhibitor BGB-11417 in Adult Patients With Mature B-cell Malignancies
Actual Study Start Date : July 5, 2021
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024

Arm Intervention/treatment
Experimental: Cohort A: R/R NHL
Participants with R/R NHL, including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL), or transformed NHL, will receive oral BGB-11417 until the MTD (or maximum ascending dose [MAD]) and the RP2D can be determined.
Drug: BGB-11417
Film-coated tablets administered orally as specified in the treatment arm.

Experimental: Cohort B: R/R CLL/SLL (low tumor burden)
Participants with low tumor burden R/R CLL/SLL will receive oral BGB-11417 until the MTD (or MAD) and the RP2D can be determined.
Drug: BGB-11417
Film-coated tablets administered orally as specified in the treatment arm.

Experimental: Cohort C: R/R CLL/SLL (high tumor burden)
Participants in this cohort will not be enrolled until the RP2D for Cohort B is established. Participants will be treated with the monotherapy ramp-up schedule and the RP2D established in Cohort B.
Drug: BGB-11417
Film-coated tablets administered orally as specified in the treatment arm.




Primary Outcome Measures :
  1. MTD Of BGB-11417 As Recommended By The Bayesian Logistic Regression Model Or The MAD [ Time Frame: Approximately 3 years ]
  2. RP2D Of BGB-11417 [ Time Frame: Approximately 3 years ]
    The RP2D will be decided by the sponsor and based on the safety monitoring committee recommendation considering totality of data.

  3. Incidence And Severity Of Treatment-emergent Adverse Events, Serious Adverse Events, Adverse Events (AEs) Leading To Discontinuation, And Dose-Limiting Toxicities (DLTs) [ Time Frame: Approximately 3 years ]
    All AEs, including DLT events, will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 (or the Grading Scale for Hematologic Toxicity in CLL Studies as appropriate).

  4. Incidence And Severity Of Tumor Lysis Syndrome-relevant Events [ Time Frame: Approximately 3 years ]

Secondary Outcome Measures :
  1. Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  2. PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To The Time Of The Last Quantifiable Concentration (AUC0-t) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  3. PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  4. PK As Assessed By Time To Maximum Observed Plasma Concentration (tmax) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  5. PK As Assessed By Terminal Half-life (t1/2) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  6. PK As Assessed By Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/F) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  7. PK As Assessed By Apparent Volume Of Distribution (Vz/F) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  8. PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To Last Measurable Concentration At Steady State (AUClast,ss) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  9. PK As Assessed By Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  10. PK As Assessed By Trough Concentration At Steady State (Ctrough,ss) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  11. PK As Assessed By Time To Maximum Observed Plasma Concentration At Steady State (tmax,ss) Of BGB-11417 [ Time Frame: Up to 24 hours postdose ]
  12. Overall Response Rate (ORR) Of BGB-11417 Monotherapy [ Time Frame: Approximately 3 years ]
    ORR will be assessed per disease-specific response assessment guidelines as determined by the investigator.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Confirmed diagnosis of only one of the following:

    Cohort A

    a. Marginal Zone Lymphoma

    i. R/R extranodal, splenic or nodal disease defined as disease that has relapsed after, or been refractory to, ≥ 1 line of anti-CD20 antibody-based chemoimmunotherapy for ≥ 2 consecutive cycles, and no effective standard therapy for MZL is available per investigator's assessment.

    ii. Active disease requiring treatment.

    b. Follicular Lymphoma

    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 has relapsed after, or been refractory to, ≥ 1 line of anti-CD20 antibody-based chemoimmunotherapy for ≥ 2 consecutive cycles, and no effective standard therapy for FL is available per investigator's assessment.

    ii. Active disease requiring treatment.

    c. Diffuse Large B-cell Lymphoma

    i. R/R DLBCL defined as disease that relapsed after, or been refractory to, at least one line of anti-CD20 antibody based chemoimmunotherapy for ≥ 2 consecutive cycles, and no effective standard therapy for DLBCL is available per investigator's assessment.

    ii. Active disease requiring treatment.

    d. Transformed indolent B-cell NHL

    i. Any lymphoma otherwise eligible for Cohort A that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter's transformation) are not eligible for Cohort A.

    ii. Active disease requiring treatment.

    Cohorts B and C

    a. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria:

    i. R/R disease defined as disease that has relapsed after, or been refractory to, ≥ 1 line of standard therapy for ≥ 2 consecutive cycles, and no effective standard therapy is available per investigator's assessment.

    ii. Requiring treatment based on IWCLL criteria.

  2. Measurable disease by computed tomography/magnetic resonance imaging, defined as:

    1. CLL: At least 1 lymph node > 1.5 centimeters (cm) in longest diameter and measurable in 2 perpendicular dimensions. For Cohort B, participants should not meet with the definition of high tumor burden, which is required for participants enrolled in Cohort C.
    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 2 perpendicular dimensions. For MZL isolated splenomegaly is considered to indicate measurable disease for this study. For SLL, participants in Cohort B should not meet with the definition of high tumor burden, which is required for participants enrolled in Cohort C.

Key Exclusion Criteria:

  1. Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer.
  2. Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results.
  3. Known central nervous system involvement by lymphoma/leukemia.
  4. Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome.
  5. Prior autologous stem cell transplant unless ≥ 3 months after transplant; or prior chimeric cell therapy unless ≥ 6 months after cell infusion.
  6. Prior allogeneic stem cell transplant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04883957


Contacts
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Contact: BeiGene 1-877-828-5568 clinicaltrials@beigene.com

Locations
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China, Beijing
Peking University First Hospital Recruiting
Beijing, Beijing, China, 100034
Peking University Peoples Hospital Recruiting
Beijing, Beijing, China, 100044
China, Guangdong
Sun Yat Sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Shenzhen Peoples Hospital Completed
Shenzhen, Guangdong, China, 518020
China, Henan
Henan Cancer Hospital Recruiting
Zhengzhou, Henan, China, 450000
China, Hubei
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Recruiting
Wuhan, Hubei, China, 430030
China, Hunan
Hunan Cancer Hospital Recruiting
Changsha, Hunan, China, 410013
China, Jiangsu
The First Affiliated Hospital of Soochow University Recruiting
Suzhou, Jiangsu, China, 215006
China, Jiangxi
The First Affiliated Hospital of Nanchang University Branch Donghu Recruiting
Nanchang, Jiangxi, China, 330006
China, Shanghai
Affiliated Zhongshan Hospital of Fudan University Recruiting
Shanghai, Shanghai, China, 200032
China, Zhejiang
The First Affiliated Hospital, Zhejiang University School of Medicine Recruiting
Hangzhou, Zhejiang, China, 310003
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Lu Zhang, M.D. BeiGene (Suzhou) Co., Ltd.
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT04883957    
Other Study ID Numbers: BGB-11417-102
First Posted: May 12, 2021    Key Record Dates
Last Update Posted: June 1, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BeiGene:
BGB-11417
Bcl-2
Pharmacokinetics
RP2D
MTD
Additional relevant MeSH terms:
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Neoplasms