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

Sponsor

BeiGene (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05294731

Collaborator

(none)

Enrollment

Locations

Arms

59.2

Anticipated Duration (Months)

8.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
B-cell Malignancy, Low-grade Non-Hodgkin Lymphoma Mantle Cell Lymphoma Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Waldenström Macroglobulinemia	Drug: BGB-16673	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

76 participants

Allocation:

N/A

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Open-Label, Dose-Escalation and Expansion Study of the Bruton Tyrosine Kinase Targeted Protein-Degrader BGB-16673 in Chinese Patients With B-Cell Malignancies

Actual Study Start Date :

Mar 24, 2022

Anticipated Primary Completion Date :

Mar 1, 2027

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 (Dose Finding) BGB-16673 will be orally administered	Drug: BGB-16673 BGB-16673 will be orally administered as per dosage needs
Experimental: Part 2 (Dose Expansion) BGB-16673 will be administered at the recommended Phase 2 dose (RP2D) that was identified in Part 1	Drug: BGB-16673 BGB-16673 will be orally administered as per dosage needs

Arm

Intervention/Treatment

Experimental: Part 1 (Dose Finding)

BGB-16673 will be orally administered

Drug: BGB-16673

BGB-16673 will be orally administered as per dosage needs

Experimental: Part 2 (Dose Expansion)

BGB-16673 will be administered at the recommended Phase 2 dose (RP2D) that was identified in Part 1

Drug: BGB-16673

BGB-16673 will be orally administered as per dosage needs

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events (AEs) [Up to 5 year]
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Recommended Phase 2 Dose (RP2D) based on Maximum tolerated dose (MTD) of BGB-16673 [Up to 5 years]
The dose recommended by the iBOIN design or the MAD and RP2D as determined by the sponsor based on the Safety Monitoring Committee's recommendation considering totality of the available clinical safety, clinical efficacy, PK, and PD dataThe

Secondary Outcome Measures

Maximum observed plasma concentration (Cmax) of BGB-16673 [Up to Week 8]
Time to reach maximum observed plasma concentration (Tmax) of BGB-16673 [Up to Week 8]
Minimum observed plasma concentration (Cmin) of BGB-16673 [Up to Week 8]
Apparent terminal elimination half life (t1/2) of BGB-16673 [Up to Week 8]
Area under the plasma-concentration curve (AUC) of BGB-16673 [Up to Week 8]
Apparent oral clearance (CL/F) of of BGB-16673 [Up to Week 8]
Apparent volume of distribution (Vz/F) of BGB-16673 [Up to Week 8]
Accumulation ratios of BGB-16673 [Up to Week 8]
Maximum observed steady state plasma concentration (Css,max) of of BGB-16673 [Up to Week 8]
Time to reach maximum observed steady state plasma concentration (Tss,max) of BGB-16673 [Up to Week 8]
Minimum observed steady state plasma concentration (Css,min) of BGB-16673 [Up to Week 8]
Steady state apparent oral plasma clearance (CL/F) of BGB-16673 [Up to Week 8]
Steady state apparent volume of distribution (Vss/F) of BGB-16673 [Up to Week 8]
BTK protein degradation in peripheral blood upon BGB-16673 monotherapy [Up to Week 4]
Overall Response Rate (ORR) [Up to 5 years]
ORR is defined as the percentage of participants with partial or complete response, as assessed using iwCLL, Owen, and Lugano criteria
Major Response Rate (MRR) [Up to 5 years]
MRR is defined as the percentage of participants who achieved complete response (CR) + very good partial response (VGPR) + partial response (PR), as assessed by iwCLL, Owen, and Lugano criteria for participants with WM only

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria

Provision of signed and dated written informed consent prior to any study, Age ≥ 18 years
ECOG Performance Status of 0 to 2
Adequate organ function of coagulation function, liver function, renal function and pancreatic function and measure disease per disease-specific response criteria
Confirmed diagnosis of R/R MZL, FL (grade 1-3a), MCL, CLL/SLL, WM and previously treated
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

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
Require ongoing systemic treatment for any other malignancy or systemic corticosteroid treatment
Receiving treatment with a strong CYP3A inhibitor or inducer, or proton-pimp inhibitors ≤ 14 days before the first dose of BGB-16673.
Current or history of central nervous involvement
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University Third Hospital	Beijing	Beijing	China	100191
2	West China Hospital of Sichuan University	Sichuan	Chengdu	China
3	Xinqiao Hospital Affiliated to The Army Medical University	Chongqing	Chongqing	China	400030
4	Sun Yat- Sen University Cancer Center (Huangpu Campus)	Guanzhou	Guangdong	China
5	Henan Cancer Hospital	Zhengzhou	Henan	China	450000
6	Shandong Cancer Hospital	Jinan	Shandong	China	250117
7	Ruijin Hospital, Shanghai JiaoTong University School of Medicine	Shanghai	Shanghai	China	200000
8	Rui Jin Hospital Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai	China
9	The First Affiliated Hospital, Zhejiang University School of Medicine	Zhejiang		China