Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader
- Conditions
- Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaWaldenström MacroglobulinemiaFollicular LymphomaNon-Hodgkin LymphomaMarginal Zone LymphomaMantle Cell LymphomaB-cell MalignancyRichter's TransformationDLBCL Unclassifiable
- Interventions
- Registration Number
- NCT05294731
- Lead Sponsor
- BeiGene
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 146
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1a Monotherapy Dose Escalation BGB-16673 BGB-16673 will be orally administered. Phase 1b Monotherapy Safety Expansion BGB-16673 BGB-16673 will be orally administered. Phase 2 Monotherapy Dose Expansion BGB-16673 BGB-16673 will be administered at the recommended Phase 2 dose (RP2D) that was identified in Part 1.
- Primary Outcome Measures
Name Time Method Phase 1a: Maximum tolerated dose (MTD) of BGB-16673 From the date of first dose of study drugs until RP2D is determined (up to approximately 37 weeks) The highest dose evaluated as recommended by the Bayesian Optimal Interval Design with Informative Prior (iBOIN) design or the maximum assessed dose (MAD).
Phase 2: Overall Response Rate (ORR) in participants with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) Up to approximately 3 years ORR is defined as the percentage of participants with partial response or better according to the Independent Review Committee (IRC) assessment and as determined by Lugano criteria.
Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs) 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) Number of participants with AEs and SAEs as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5 (NCI CTCAE 5.0), including AEs that meet protocol-defined dose-limiting toxicity (DLT) criteria.
Phase 1: Recommended Phase 2 dose (RP2D) of BGB-16673 From the date of first dose of study drugs until RP2D is determined (up to approximately 37 weeks) As determined by the sponsor based on the Safety Monitoring Committee's recommendation considering totality of the available clinical safety, clinical efficacy, pharmacokinetics, and pharmacodynamics data.
Phase 2: ORR in participants with R/R Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Up to approximately 3 years ORR is defined as the percentage of participants with partial response or better as assessed by the IRC and determined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for CLL and by Lugano criteria for SLL
- Secondary Outcome Measures
Name Time Method Maximum observed plasma concentration (Cmax) After a Single Dose of BGB-16673 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 Time to reach maximum observed plasma concentration (Tmax) After a Single Dose of BGB-16673 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 Minimum observed plasma concentration (Cmin) After a Single Dose of BGB-16673 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 Apparent terminal elimination half-life (t1/2) After a Single Dose of BGB-16673 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 Area under the plasma-concentration curve (AUC) After a Single Dose of BGB-16673 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 Apparent oral clearance (CL/F) After a Single Dose of BGB-16673 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 Apparent volume of distribution (Vz/F) After a Single Dose of BGB-16673 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 Maximum observed steady state plasma concentration (Css,max) of of BGB-16673 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 Time to reach maximum observed steady state plasma concentration (Tss,max) of BGB-16673 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 Minimum observed steady state plasma concentration (Css,min) of BGB-16673 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 Steady state area under the plasma concentration-time curve (AUC) of BGB-16673 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 Accumulation ratios of Cmax and AUC of BGB-16673 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 Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy 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 Phase 1: Overall Response Rate (ORR) Up to approximately 3 years ORR is defined as the percentage of participants with partial or complete response, as assessed by the investigator using International Workshop on Chronic Lymphocytic Leukemia (iwCLL), Owen, and Lugano criteria.
Phase 1: Major Response Rate (MRR) in participants with Waldenstrom macroglobulinemia (WM) Up to approximately 3 years MRR is defined as the percentage of participants who achieved complete response (CR), very good partial response (VGPR), and partial response (PR), as assessed by investigators for participants with WM only.
Phase 2: Number of participants with AEs and SAEs 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) Number of participants with AEs and SAEs as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5 (NCI CTCAE 5.0).
Phase 2: ORR in participants with R/R MCL as assessed by investigators Up to approximately 3 years ORR is defined as the percentage of participants with partial response or better according to investigators and as determined by Lugano criteria.
Phase 2: Duration of Response (DOR) Up to approximately 3 years DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first as determined by IRC and by investigators.
Phase 2: Time to Response (TTR) Up to approximately 3 years TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better) as determined by IRC and by investigators.
Phase 2: Progression Free Survival (PFS) Up to approximately 3 years PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as determined by IRC and by investigators.
Phase 2: Overall Survival (OS) Up to approximately 3 years OS is defined as the time from first study drug administration to the date of death due to any cause.
Phase 2: Best Overall Response (BOR) of Partial Response with Lymphocytosis (PR-L) in Participants with R/R CLL/SLL Up to approximately 3 years BOR of PR-L or better as determined by IRC and by investigators per iwCLL criteria for CLL and per Lugano criteria for SLL
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 Baseline and Day 1 of weeks 5, 13, 25, and 37 The NFLymSI-18 questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and is divided into a total score. A mixed model for repeated measures (MMRM) will be used to estimate the mean change from baseline for NFlymSI-18 subscales of Disease-Related Symptoms Physical (DRSP), and "treatment side effects" (TSE).
Phase 2: ORR assessed by the Investigator in participants with R/R CLL/SLL Up to approximately 3 years ORR is defined as the percentage of participants with partial response or better as determined by investigators per iwCLL criteria for CLL and Lugano criteria for SLL.
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 Baseline and Day 1 of weeks 5, 13, 25, and 37 FACT-Leu is a 44-item patient reported outcome questionnaire with five subscales used to measure health-related quality of life (HRQoL) in leukemia patients. Each question is scored from 0 (not at all) to 4 (very much).
Trial Locations
- Locations (29)
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Beijing Chao Yang Hospital,Capital Medical University
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Bengbu Medical University
🇨🇳Bengbu, Anhui, China
Second Affiliated Hospital of Army Medical University (Xinqiao Hospital)
🇨🇳Chongqing, Chongqing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Sun Yat Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Guangdong Provincial Peoples Hospital Huifu Branch
🇨🇳Guangzhou, Guangdong, China
The Peoples Hospital of Guangxi Zhuang Autonomous Region
🇨🇳Nanning, Guangxi, China
Nanyang Central Hospital
🇨🇳Nanyang, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Xiangyang Central Hospital
🇨🇳Xiangyang, Hubei, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
Jiangxi Province Cancer Hospital
🇨🇳Nanchang, Jiangxi, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Affiliated Zhongshan Hospital of Dalian University
🇨🇳Dalian, Liaoning, China
Shandong Cancer Hospital
🇨🇳Jinan, Shandong, China
Qingdao Central Hospital
🇨🇳Qingdao, Shandong, China
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Shanxi Provincial Cancer Hospital
🇨🇳Taiyuan, Shanxi, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Institute of Hematology and Hospital of Blood Disease
🇨🇳Tianjin, Tianjin, China
First Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China
The First Affiliated Hospital, Zhejiang University School of Medicine Branch Yuhang
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China