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): 127
• 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 College
    • Hefei, Anhui, China, 230000
      • Recruiting
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Chao Yang Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • Recruiting
      • Xinqiao Hospital Affiliated to the Army Medical University
  • 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
  • Henan
    • 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
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
    • Wuxi, Jiangsu, China, 214023
      • Recruiting
      • Wuxi Peoples Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • 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
    • Shanghai, Shanghai, 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
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology and Hospital of Blood Disease
  • Zhejiang
    • Hangzhou, Zhejiang, China, 311121
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine Branch Yuhang

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, Age ≥ 18 years
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. Confirmed diagnosis of R/R Marginal Zone Lymphoma (MZL), Follicular Lymphoma (grade 1-3a), Mantle cell lymphoma (MCL), Chronic lymphocytic leukemia, small lymphocytic lymphoma, WM, diffuse large B-cell lymphoma (DLBCL) (part 1a only), or Richter's transformation to DLBCL (part 1a only).
5. 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, or proton-pimp inhibitors ≤ 14 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: Part 1a Monotherapy Dose Escalation; BGB-16673 will be orally administered	Drug: BGB-16673; Orally administered
Experimental: Part 1b Monotherapy Safety Expansion; BGB-16673 will be orally administered	Drug: BGB-16673; Orally administered
Experimental: Part 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
Part 1: Number of participants with adverse events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results.	Up to 5 years
Part 1: 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 Mean absolute deviation (MAD) (Part 1a only)	Up to 5 years
Part 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	Up to 5 years
Part 2: Overall Response Rate (ORR) in participants with replapsed/refractory (R/R) Mantle Cell Lymphoma (MCL)	ORR is defined as the percentage of participants with partial response or better according to Independent Review Commitee (IRC) assessment and as determined by Lugano criteria	Up to 5 years
Part 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 investigators and determined by iwCLL criteria	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax) of BGB-16673		Up to Week 9
Time to reach maximum observed plasma concentration (Tmax) of BGB-16673		Up to Week 9
Minimum observed plasma concentration (Cmin) of BGB-16673		Up to Week 9
Apparent terminal elimination half life (t1/2) of BGB-16673		Up to Week 9
Area under the plasma-concentration curve (AUC) of BGB-16673		Up to Week 9
Apparent oral clearance (CL/F) of of BGB-16673		Up to Week 9
Apparent volume of distribution (Vz/F) of BGB-16673		Up to Week 9
Accumulation ratios of BGB-16673		Up to Week 9
Maximum observed steady state plasma concentration (Css,max) of of BGB-16673		Up to Week 9
Time to reach maximum observed steady state plasma concentration (Tss,max) of BGB-16673		Up to Week 9
Minimum observed steady state plasma concentration (Css,min) of BGB-16673		Up to Week 9
Steady state apparent volume of distribution (Vss/F) of BGB-16673		Up to Week 9
Overall Response Rate (ORR)	ORR is defined as the percentage of participants with partial or complete response, as assessed using International Workshop on Chronic Lymphocytic Leukemia (iwCLL), Owen, and Lugano criteria	Up to 5 years
Steady state apparent oral plasma clearance (CLss/F) of BGB-16673		Up to Week 9
Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy		Up to Week 9
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) + partial response (PR), as assessed by investigators for participants with WM only	Up to 5 years
Part 2: Number of participants with adverse events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results.	Up to 5 years
Part 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 5 years
Part 2: Time to Response (TRR)	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 5 years
Part 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 5 years
Part 2: Overall Survival (OS)	OS is defined as the time from first study drug administration to the date of death due to any cause as determined by IRC and by investigators	Up to 5 years
Part 2: Participant Reported Outcomes (PRO) as measured by NFLymSI-18 in participants with R/R MCL	The National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index-18 (FLymSI-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.	Up to 5 years

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

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 (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: DLBCL; FL; MZL; BTK; Richter's Transformation; B-cell Malignancy; CDAC; degrader; degradation
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Chronic Disease; Neoplasms; Lymphoma; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell
• 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

Drug and device information, study documents

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