Clinical trial NCT05294731: Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader
Official title: A Phase 1/2, Open-Label, Dose-Escalation and Expansion Study of the Bruton Tyrosine Kinase-Targeted Protein-Degrader BGB-16673 in Chinese Patients With B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Malignancy
Non-Hodgkin Lymphoma
Mantle Cell Lymphoma
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Waldenström Macroglobulinemia
Marginal Zone Lymphoma
Follicular Lymphoma
DLBCL Unclassifiable
Richter's Transformation
Keywords: B-cell Malignancy
MZL
FL
DLBCL
Richter's Transformation
CDAC
BTK
degrader
BGB-16673
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2022-03-24
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to explore the recommended phase 2 dose and evaluate the safety, tolerability and preliminary antitumor activity of BGB-16673 monotherapy at the recommended Phase 2 dose for the selected B-cell malignancy expansion cohorts


Eligibility criteria: Key Inclusion Criteria

1. Provision of signed and dated written informed consent prior to any study
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
3. Adequate organ function of coagulation function, liver function, renal function and pancreatic function and measure disease per disease-specific response criteria
4. Phase 1: Confirmed diagnosis of R/R Marginal Zone Lymphoma (MZL), Follicular Lymphoma (grade 1-3a), Waldenström Macroglobulinemia (WM), non-germinal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL), Richter's transformation to DLBCL, MCL, or CLL/SLL
5. Phase 2: Confirmed diagnosis of MCL, or CLL/SLL
6. Highly effective method of birth control during study treatment period, and for at least 90 days after the last dose of the study drug

Key Exclusion Criteria

1. Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer
2. Require ongoing systemic treatment for any other malignancy or systemic corticosteroid treatment
3. Receiving treatment with a strong CYP3A inhibitor or inducer ≤ 14 days before the first dose of BGB-16673, or proton-pump inhibitors ≤ 5 days before the first dose of BGB-16673.
4. Current or history of central nervous involvement
5. Prior autologous stem cell transplant unless ≥ 3 months after transplant, prior chimeric cell therapy unless ≥ 6 months after cell infusion, prior allogeneic stem cell transplant ≤ 6 months before the first dose of the study drug

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From first dose of the study drug(s) to 30 days after the last dose or before initiation of a new anticancer therapy, whichever occurs first (up to approximately 3 years)
measure: Phase 1: Recommended Phase 2 dose (RP2D) of BGB-16673
timeFrame: From the date of first dose of study drugs until RP2D is determined (up to approximately 37 weeks)
measure: Phase 1a: Maximum tolerated dose (MTD) of BGB-16673
timeFrame: From the date of first dose of study drugs until RP2D is determined (up to approximately 37 weeks)
measure: Phase 2: Overall Response Rate (ORR) in participants with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL)
timeFrame: Up to approximately 3 years
measure: Phase 2: ORR in participants with R/R Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) After a Single Dose of BGB-16673
timeFrame: Phase 1a: Week 1 Day 1 pre-dose up to 72 hours post-dose; Phase 1b: Week 1 Day 1 pre-dose and up to 6 hours post-dose; Phase 2: Week 1 Day 1 pre-dose and up to 8 hours post-dose
measure: Time to reach maximum observed plasma concentration (Tmax) After a Single Dose of BGB-16673
timeFrame: Phase 1a: Week 1 Day 1 pre-dose up to 72 hours post-dose; Phase 1b: Week 1 Day 1 pre-dose and up to 6 hours post-dose; Phase 2: Week 1 Day 1 pre-dose and up to 8 hours post-dose
measure: Minimum observed plasma concentration (Cmin) After a Single Dose of BGB-16673
timeFrame: Phase 1a: Week 1 Day 1 pre-dose up to 72 hours post-dose; Phase 1b: Week 1 Day 1 pre-dose and up to 6 hours post-dose; Phase 2: Week 1 Day 1 pre-dose and up to 8 hours post-dose
measure: Apparent terminal elimination half-life (t1/2) After a Single Dose of BGB-16673
timeFrame: Phase 1a: Week 1 Day 1 pre-dose up to 72 hours post-dose; Phase 1b: Week 1 Day 1 pre-dose and up to 6 hours post-dose; Phase 2: Week 1 Day 1 pre-dose and up to 8 hours post-dose
measure: Area under the plasma-concentration curve (AUC) After a Single Dose of BGB-16673
timeFrame: Phase 1a: Week 1 Day 1 pre-dose up to 72 hours post-dose; Phase 1b: Week 1 Day 1 pre-dose and up to 6 hours post-dose; Phase 2: Week 1 Day 1 pre-dose and up to 8 hours post-dose
measure: Apparent oral clearance (CL/F) After a Single Dose of BGB-16673
timeFrame: Phase 1a: Week 1 Day 1 pre-dose up to 72 hours post-dose; Phase 1b: Week 1 Day 1 pre-dose and up to 6 hours post-dose; Phase 2: Week 1 Day 1 pre-dose and up to 8 hours post-dose
measure: Apparent volume of distribution (Vz/F) After a Single Dose of BGB-16673
timeFrame: Phase 1a: Week 1 Day 1 pre-dose up to 72 hours post-dose; Phase 1b: Week 1 Day 1 pre-dose and up to 6 hours post-dose; Phase 2: Week 1 Day 1 pre-dose and up to 8 hours post-dose
measure: Maximum observed steady state plasma concentration (Css,max) of of BGB-16673
timeFrame: Phase 1a and Phase 2: Week 5 Day 1 pre-dose and up to 8 hours post-dose; Phase 1b: Week 5 Day 1 pre-dose and up to 6 hours post-dose
measure: Time to reach maximum observed steady state plasma concentration (Tss,max) of BGB-16673
timeFrame: Phase 1a and Phase 2: Week 5 Day 1 pre-dose and up to 8 hours post-dose; Phase 1b: Week 5 Day 1 pre-dose and up to 6 hours post-dose
measure: Minimum observed steady state plasma concentration (Css,min) of BGB-16673
timeFrame: Phase 1a and Phase 2: Week 5 Day 1 pre-dose and up to 8 hours post-dose; Phase 1b: Week 5 Day 1 pre-dose and up to 6 hours post-dose
measure: Steady state area under the plasma concentration-time curve (AUC) of BGB-16673
timeFrame: Phase 1a and Phase 2: Week 5 Day 1 pre-dose and up to 8 hours post-dose; Phase 1b: Week 5 Day 1 pre-dose and up to 6 hours post-dose
measure: Accumulation ratios of Cmax and AUC of BGB-16673
timeFrame: Phase 1a: Day 1 pre-dose up to 72 hours post-dose, Week 5 pre-dose up to 8 hours post-dose; Phase 1b: Week 1 and Week 5 pre-dose up to 6 hours post-dose; Phase 2: Week 1 and Week 5 pre-dose up to 8 hours post-dose
measure: Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy
timeFrame: Phase 1a: Day 1 pre-dose up to 72 hours post-dose, Week 5 pre-dose and 8 hours post-dose, Week 9 pre-dose; Phase 1b: Week 1 and Week 5 pre-dose and 6 hours post-dose, Week 9 pre-dose; Phase 2: Week 1, Week 5, Week 9 pre-dose
measure: Phase 1: Overall Response Rate (ORR)
timeFrame: Up to approximately 3 years
measure: Phase 1: Major Response Rate (MRR) in participants with Waldenstrom macroglobulinemia (WM)
timeFrame: Up to approximately 3 years
measure: Phase 2: Number of participants with AEs and SAEs
timeFrame: From first dose of the study drug(s) to 30 days after the last dose or before initiation of a new anticancer therapy, whichever occurs first (up to approximately 3 years)
measure: Phase 2: ORR in participants with R/R MCL as assessed by investigators
timeFrame: Up to approximately 3 years
measure: Phase 2: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
measure: Phase 2: Time to Response (TTR)
timeFrame: Up to approximately 3 years
measure: Phase 2: Progression Free Survival (PFS)
timeFrame: Up to approximately 3 years
measure: Phase 2: Overall Survival (OS)
timeFrame: Up to approximately 3 years
measure: Phase 2: Best Overall Response (BOR) of Partial Response with Lymphocytosis (PR-L) in Participants with R/R CLL/SLL
timeFrame: Up to approximately 3 years
measure: Phase 2: Change from baseline in National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index-18 (NFLymSI-18) Disease-related Symptom Physical and Treatment Side Effect Subscales in participants with R/R MCL
timeFrame: Baseline and Day 1 of weeks 5, 13, 25, and 37
measure: Phase 2: ORR assessed by the Investigator in participants with R/R CLL/SLL
timeFrame: Up to approximately 3 years
measure: Phase 2: Mean change from baseline for the Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu ) questionnaire Physical Well-being and Functional Well-being Subscales for participants with R/R CLL/SLL
timeFrame: Baseline and Day 1 of weeks 5, 13, 25, and 37
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical University
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chao Yang Hospital,Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Second Affiliated Hospital of Army Medical University (Xinqiao Hospital)
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital Huifu Branch
state: Guangdong
city: Nanning
country: China
facility: The Peoples Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
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: Nanchang
country: China
facility: Jiangxi Province Cancer Hospital
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: Affiliated Zhongshan Hospital of Dalian University
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology and Hospital of Blood Disease
state: Tianjin
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine Branch Yuhang
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: