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

Mature B-cell Malignancies Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04883957
• Other study ID #: BGB-11417-102
• Secondary ID: CTR20211017
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 5, 2021
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 64
• Est. completion date: April 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Mature B-cell Malignancies
• Neoplasms

Intervention

Drug:
• BGB-11417
Film-coated tablets administered orally as specified in the treatment arm.

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing	Beijing
China	Peking University Peoples Hospital	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	Sun Yat Sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Nanchang University Branch Donghu	Nanchang	Jiangxi
China	Affiliated Zhongshan Hospital of Fudan University	Shanghai	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD Of BGB-11417 As Recommended By The Bayesian Logistic Regression Model Or The MAD		Approximately 3 years
Primary	RP2D Of BGB-11417	The RP2D will be decided by the sponsor and based on the safety monitoring committee recommendation considering totality of data.	Approximately 3 years
Primary	Incidence And Severity Of Treatment-emergent Adverse Events, Serious Adverse Events, Adverse Events (AEs) Leading To Discontinuation, And Dose-Limiting Toxicities (DLTs)	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).	Approximately 3 years
Primary	Incidence And Severity Of Tumor Lysis Syndrome-relevant Events		Approximately 3 years
Secondary	Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of BGB-11417		Up to 24 hours postdose
Secondary	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
Secondary	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
Secondary	PK As Assessed By Time To Maximum Observed Plasma Concentration (tmax) Of BGB-11417		Up to 24 hours postdose
Secondary	PK As Assessed By Terminal Half-life (t1/2) Of BGB-11417		Up to 24 hours postdose
Secondary	PK As Assessed By Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/F) Of BGB-11417		Up to 24 hours postdose
Secondary	PK As Assessed By Apparent Volume Of Distribution (Vz/F) Of BGB-11417		Up to 24 hours postdose
Secondary	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
Secondary	PK As Assessed By Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of BGB-11417		Up to 24 hours postdose
Secondary	PK As Assessed By Trough Concentration At Steady State (Ctrough,ss) Of BGB-11417		Up to 24 hours postdose
Secondary	PK As Assessed By Time To Maximum Observed Plasma Concentration At Steady State (tmax,ss) Of BGB-11417		Up to 24 hours postdose
Secondary	Overall Response Rate (ORR) Of BGB-11417 Monotherapy	ORR will be assessed per disease-specific response assessment guidelines as determined by the investigator.	Approximately 3 years