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

Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05294731
• Other study ID #: BGB-16673-102
• Secondary ID: CTR20220399
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 24, 2022
• Est. completion date: March 2027

Study information

• Verified date: May 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: 1.877.828.5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 127
• Est. completion date: March 2027
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. 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

Related Conditions & MeSH terms

• B-cell Malignancy
• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• DLBCL Unclassifiable
• Follicular Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma
• Neoplasms
• Non-Hodgkin Lymphoma
• Richter's Transformation
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• BGB-16673
Orally administered

Locations

Country	Name	City	State
China	Beijing Chao Yang Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Xinqiao Hospital Affiliated to the Army Medical University	Chongqing	Chongqing
China	Affiliated Zhongshan Hospital of Dalian University	Dalian	Liaoning
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Guangdong Provincial Peoples Hospital Huifu Branch	Guangzhou	Guangdong
China	Sun Yat Sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University School of Medicine Branch Yuhang	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	Shandong Cancer Hospital	Jinan	Shandong
China	The First Affiliated Hospital of Nanchang University Branch Donghu	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanyang Central Hospital	Nanyang	Henan
China	Qingdao Central Hospital	Qingdao	Shandong
China	Rui Jin Hospital Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	Institute of Hematology and Hospital of Blood Disease	Tianjin	Tianjin
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Wuxi Peoples Hospital	Wuxi	Jiangsu
China	Xiangyang Central Hospital	Xiangyang	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	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
Primary	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
Primary	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
Primary	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
Primary	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	Maximum observed plasma concentration (Cmax) of BGB-16673		Up to Week 9
Secondary	Time to reach maximum observed plasma concentration (Tmax) of BGB-16673		Up to Week 9
Secondary	Minimum observed plasma concentration (Cmin) of BGB-16673		Up to Week 9
Secondary	Apparent terminal elimination half life (t1/2) of BGB-16673		Up to Week 9
Secondary	Area under the plasma-concentration curve (AUC) of BGB-16673		Up to Week 9
Secondary	Apparent oral clearance (CL/F) of of BGB-16673		Up to Week 9
Secondary	Apparent volume of distribution (Vz/F) of BGB-16673		Up to Week 9
Secondary	Accumulation ratios of BGB-16673		Up to Week 9
Secondary	Maximum observed steady state plasma concentration (Css,max) of of BGB-16673		Up to Week 9
Secondary	Time to reach maximum observed steady state plasma concentration (Tss,max) of BGB-16673		Up to Week 9
Secondary	Minimum observed steady state plasma concentration (Css,min) of BGB-16673		Up to Week 9
Secondary	Steady state apparent oral plasma clearance (CLss/F) of BGB-16673		Up to Week 9
Secondary	Steady state apparent volume of distribution (Vss/F) of BGB-16673		Up to Week 9
Secondary	Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy		Up to Week 9
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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