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

Study Overview
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Brief Summary
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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

Official Title
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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

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

Intervention / Treatment
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* Drug: BGB-16673


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Provision of signed and dated written informed consent prior to any study, Age ≥ 18 years Eastern Cooperative Oncology Group (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 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). 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1a Monotherapy Dose Escalation<br>BGB-16673 will be orally administered | Drug: BGB-16673<br>* BGB-16673 will be orally administered as per dosage needs<br>|
| Experimental: Part 1b Monotherapy Safety Expansion<br>BGB-16673 will be orally administered | Drug: BGB-16673<br>* BGB-16673 will be orally administered as per dosage needs<br>|
| Experimental: Part 2 Monotherapy Dose Expansion<br>BGB-16673 will be administered at the recommended Phase 2 dose (RP2D) that was identified in Part 1 | Drug: BGB-16673<br>* BGB-16673 will be orally administered as per dosage needs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

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 oral plasma clearance (CL/F) of BGB-16673 |  | Up to Week 9 | 
| Steady state apparent volume of distribution (Vss/F) of BGB-16673 |  | Up to Week 9 | 
| Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood upon BGB-16673 monotherapy |  | 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 | 
| Major Response Rate (MRR) | 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 Waldenstrom macroglobulinemia (WM) only | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MZL, B-cell Malignancy, FL, DLBCL, Richter's Transformation