Clinical trial NCT04883957: Study of BGB-11417 in Adult Participants With Mature B-cell Malignancies
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Mature B-cell Malignancies
Keywords: BGB-11417
Bcl-2
Pharmacokinetics
RP2D
MTD
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2021-05-12
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: MTD Of BGB-11417 As Recommended By The Bayesian Logistic Regression Model Or The MAD
timeFrame: Approximately 3 years
measure: RP2D Of BGB-11417
timeFrame: Approximately 3 years
measure: Incidence And Severity Of Treatment-emergent Adverse Events, Serious Adverse Events, Adverse Events (AEs) Leading To Discontinuation, And Dose-Limiting Toxicities (DLTs)
timeFrame: Approximately 3 years
measure: Incidence And Severity Of Tumor Lysis Syndrome-relevant Events
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of BGB-11417
timeFrame: Up to 24 hours postdose
measure: 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
timeFrame: Up to 24 hours postdose
measure: PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) Of BGB-11417
timeFrame: Up to 24 hours postdose
measure: PK As Assessed By Time To Maximum Observed Plasma Concentration (tmax) Of BGB-11417
timeFrame: Up to 24 hours postdose
measure: PK As Assessed By Terminal Half-life (t1/2) Of BGB-11417
timeFrame: Up to 24 hours postdose
measure: PK As Assessed By Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/F) Of BGB-11417
timeFrame: Up to 24 hours postdose
measure: PK As Assessed By Apparent Volume Of Distribution (Vz/F) Of BGB-11417
timeFrame: Up to 24 hours postdose
measure: 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
timeFrame: Up to 24 hours postdose
measure: PK As Assessed By Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of BGB-11417
timeFrame: Up to 24 hours postdose
measure: PK As Assessed By Trough Concentration At Steady State (Ctrough,ss) Of BGB-11417
timeFrame: Up to 24 hours postdose
measure: PK As Assessed By Time To Maximum Observed Plasma Concentration At Steady State (tmax,ss) Of BGB-11417
timeFrame: Up to 24 hours postdose
measure: Overall Response Rate (ORR) Of BGB-11417 Monotherapy
timeFrame: Approximately 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Peoples Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Peoples Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: BeiGene (Suzhou) Co., Ltd.
name: Lu Zhang, M.D.
role: STUDY_DIRECTOR
References: