Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader

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

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

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Waldenström Macroglobulinemia; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Non-Hodgkin Lymphoma; B-cell Malignancy; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Richter's Transformation; DLBCL Unclassifiable
• Intervention / Treatment: Drug: BGB-16673

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: 1.877.828.5568; Email: clinicaltrials@beigene.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • Recruiting
      • The First Affiliated Hospital of Bengbu Medical University
    • Hefei, Anhui, China, 230000
      • Recruiting
      • Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100000
      • Recruiting
      • Peking University Third Hospital
    • Beijing, Beijing Municipality, China, 100020
      • Recruiting
      • Beijing Chao Yang Hospital,Capital Medical University
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400037
      • Recruiting
      • Second Affiliated Hospital of Army Medical University (Xinqiao Hospital)
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat Sen University Cancer Center
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Guangdong Provincial Peoples Hospital Huifu Branch
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Recruiting
      • The Peoples Hospital of Guangxi Zhuang Autonomous Region
  • Henan
    • Nanyang, Henan, China, 473000
      • Recruiting
      • Nanyang Central Hospital
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Xiangyang, Hubei, China, 441021
      • Recruiting
      • Xiangyang Central Hospital
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • The second Xiangya hospital of central south university
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of Nanchang University Branch Donghu
    • Nanchang, Jiangxi, China, 330029
      • Recruiting
      • Jiangxi Province Cancer Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China, 116001
      • Recruiting
      • Affiliated Zhongshan Hospital of Dalian University
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital
    • Qingdao, Shandong, China, 266031
      • Recruiting
      • Qingdao Central Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Recruiting
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Recruiting
      • Shanxi Provincial Cancer hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Recruiting
      • Institute of Hematology and Hospital of Blood Disease
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • Recruiting
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 311121
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine Branch Yuhang
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a Monotherapy Dose Escalation; BGB-16673 will be orally administered.	Drug: BGB-16673; Orally administered
Experimental: Phase 1b Monotherapy Safety Expansion; BGB-16673 will be orally administered.	Drug: BGB-16673; Orally administered
Experimental: Phase 2 Monotherapy Dose Expansion; BGB-16673 will be administered at the recommended Phase 2 dose (RP2D) that was identified in Part 1.	Drug: BGB-16673; Orally administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	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.	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)
Phase 1: Recommended Phase 2 dose (RP2D) of BGB-16673	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.	From the date of first dose of study drugs until RP2D is determined (up to approximately 37 weeks)
Phase 1a: Maximum tolerated dose (MTD) of BGB-16673	The highest dose evaluated as recommended by the Bayesian Optimal Interval Design with Informative Prior (iBOIN) design or the maximum assessed dose (MAD).	From the date of first dose of study drugs until RP2D is determined (up to approximately 37 weeks)
Phase 2: Overall Response Rate (ORR) in participants with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL)	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.	Up to approximately 3 years
Phase 2: ORR in participants with R/R Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)	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	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Up to approximately 3 years
Phase 1: Major Response Rate (MRR) in participants with Waldenstrom macroglobulinemia (WM)	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.	Up to approximately 3 years
Phase 2: Number of participants with AEs and SAEs	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).	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)
Phase 2: ORR in participants with R/R MCL as assessed by investigators	ORR is defined as the percentage of participants with partial response or better according to investigators and as determined by Lugano criteria.	Up to approximately 3 years
Phase 2: Duration of Response (DOR)	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.	Up to approximately 3 years
Phase 2: Time to Response (TTR)	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.	Up to approximately 3 years
Phase 2: Progression Free Survival (PFS)	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.	Up to approximately 3 years
Phase 2: Overall Survival (OS)	OS is defined as the time from first study drug administration to the date of death due to any cause.	Up to approximately 3 years
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	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).	Baseline and Day 1 of weeks 5, 13, 25, and 37
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	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).	Baseline and Day 1 of weeks 5, 13, 25, and 37
Phase 2: Best Overall Response (BOR) of Partial Response with Lymphocytosis (PR-L) in Participants with R/R CLL/SLL	BOR of PR-L or better as determined by IRC and by investigators per iwCLL criteria for CLL and per Lugano criteria for SLL	Up to approximately 3 years
Phase 2: ORR assessed by the Investigator in participants with R/R CLL/SLL	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.	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2022
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2029

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: DLBCL; FL; MZL; BTK; Richter's Transformation; B-cell Malignancy; CDAC; degrader; BGB-16673
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone
• Other Study ID Numbers: BGB-16673-102; CTR20220399 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No