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
Overview
- Phase
- Phase 1
- Intervention
- BGB-11417
- Conditions
- Mature B-cell Malignancies
- Sponsor
- BeiGene
- Enrollment
- 64
- Locations
- 22
- Primary Endpoint
- MTD Of BGB-11417 As Recommended By The Bayesian Logistic Regression Model Or The MAD
- Status
- Active, not recruiting
- Last Updated
- 12 days ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed diagnosis of only one of the following:
- •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.
Exclusion Criteria
- •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.
- •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.
- •Known central nervous system involvement by lymphoma/leukemia.
- •Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome.
- •Prior autologous stem cell transplant unless ≥ 3 months after transplant; or prior chimeric cell therapy unless ≥ 6 months after cell infusion.
- •Prior allogeneic stem cell transplant.
Arms & Interventions
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.
Intervention: BGB-11417
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.
Intervention: BGB-11417
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.
Intervention: BGB-11417
Outcomes
Primary Outcomes
MTD Of BGB-11417 As Recommended By The Bayesian Logistic Regression Model Or The MAD
Time Frame: Approximately 3 years
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.
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).
Incidence And Severity Of Tumor Lysis Syndrome-relevant Events
Time Frame: Approximately 3 years
MTD Of BGB-11417 As Recommended By The Bayesian Logistic Regression Model Or The MAD
Time Frame: Approximately 3 years
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.
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).
Incidence And Severity Of Tumor Lysis Syndrome-relevant Events
Time Frame: Approximately 3 years
Secondary Outcomes
- PK As Assessed By Time To Maximum Observed Plasma Concentration At Steady State (tmax,ss) Of BGB-11417(Up to 24 hours postdose)
- Overall Response Rate (ORR) Of BGB-11417 Monotherapy(Approximately 3 years)
- Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of BGB-11417(Up to 24 hours postdose)
- 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(Up to 24 hours postdose)
- PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Time To Maximum Observed Plasma Concentration (tmax) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Terminal Half-life (t1/2) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/F) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Apparent Volume Of Distribution (Vz/F) Of BGB-11417(Up to 24 hours postdose)
- 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(Up to 24 hours postdose)
- PK As Assessed By Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Trough Concentration At Steady State (Ctrough,ss) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Trough Concentration At Steady State (Ctrough,ss) Of BGB-11417(Up to 24 hours postdose)
- Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of BGB-11417(Up to 24 hours postdose)
- 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(Up to 24 hours postdose)
- PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Time To Maximum Observed Plasma Concentration (tmax) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Terminal Half-life (t1/2) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/F) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Apparent Volume Of Distribution (Vz/F) Of BGB-11417(Up to 24 hours postdose)
- 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(Up to 24 hours postdose)
- PK As Assessed By Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Time To Maximum Observed Plasma Concentration At Steady State (tmax,ss) Of BGB-11417(Up to 24 hours postdose)
- Overall Response Rate (ORR) Of BGB-11417 Monotherapy(Approximately 3 years)