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

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

Overview

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

Interventions

• Drug BGB-16673
  Orally administered

Primary outcome measures

• Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Time frame: 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 [Time frame: 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 [Time frame: 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) [Time frame: Up to approximately 3 years]
• Phase 2: ORR in participants with R/R Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) [Time frame: Up to approximately 3 years]

Secondary outcome measures (12)

• Maximum observed plasma concentration (Cmax) After a Single Dose of BGB-16673 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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]

Eligibility criteria

Inclusion criteria

• Provision of signed and dated written informed consent prior to any study
• 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
• 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
• Phase 2: Confirmed diagnosis of MCL, or CLL/SLL
• Highly effective method of birth control during study treatment period, and for at least 90 days after the last dose of the study drug

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 ≤ 14 days before the first dose of BGB-16673, or proton-pump inhibitors ≤ 5 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 29 centers

• The First Affiliated Hospital of Bengbu Medical University — Bengbu
• Anhui Provincial Hospital — Hefei
• Peking University Third Hospital — Beijing
• Beijing Chao Yang Hospital,Capital Medical University — Beijing
• Second Affiliated Hospital of Army Medical University (Xinqiao Hospital) — Chongqing
• Fujian Medical University Union Hospital — Fuzhou
• Sun Yat Sen University Cancer Center — Guangzhou
• Guangdong Provincial Peoples Hospital Huifu Branch — Guangzhou
• … and 21 more centers

Identifiers

NCT: NCT05294731 · BGB-16673-102 · CTR20220399

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20220399 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗