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
概览
- 阶段
- 1 期
- 干预措施
- BGB-16673
- 疾病 / 适应症
- B-cell Malignancy
- 发起方
- BeiGene
- 入组人数
- 146
- 试验地点
- 50
- 主要终点
- Phase 1a: Maximum tolerated dose (MTD) of BGB-16673
- 状态
- 招募中
- 最后更新
- 15天前
概览
简要总结
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
研究者
入排标准
入选标准
- •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
排除标准
- •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-
- •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
研究组 & 干预措施
Phase 1a Monotherapy Dose Escalation
BGB-16673 will be orally administered.
干预措施: BGB-16673
Phase 1b Monotherapy Safety Expansion
BGB-16673 will be orally administered.
干预措施: BGB-16673
Phase 2 Monotherapy Dose Expansion
BGB-16673 will be administered at the recommended Phase 2 dose (RP2D) that was identified in Part 1.
干预措施: BGB-16673
结局指标
主要结局
Phase 1a: Maximum tolerated dose (MTD) of BGB-16673
时间窗: From the date of first dose of study drugs until RP2D is determined (up to approximately 37 weeks)
The highest dose evaluated as recommended by the Bayesian Optimal Interval Design with Informative Prior (iBOIN) design or the maximum assessed dose (MAD).
Phase 2: Overall Response Rate (ORR) in participants with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL)
时间窗: Up to approximately 3 years
ORR is defined as the percentage of participants with partial response or better according to the Independent Review Committee (IRC) assessment and as determined by Lugano criteria.
Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
时间窗: 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)
Number of participants with AEs and SAEs as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5 (NCI CTCAE 5.0), including AEs that meet protocol-defined dose-limiting toxicity (DLT) criteria.
Phase 1: Recommended Phase 2 dose (RP2D) of BGB-16673
时间窗: From the date of first dose of study drugs until RP2D is determined (up to approximately 37 weeks)
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.
Phase 2: ORR in participants with R/R Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
时间窗: Up to approximately 3 years
ORR is defined as the percentage of participants with partial response or better as assessed by the IRC and determined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for CLL and by Lugano criteria for SLL
次要结局
- Maximum observed plasma concentration (Cmax) After a Single Dose of BGB-16673(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(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(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(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(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(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(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(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(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(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(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(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)
- Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy(Phase 1a: Day 1 pre-dose up to 72 hours post-dose, Week 5 pre-dose and 8 hours post-dose, Week 9 pre-dose; Phase 1b: Week 1 and Week 5 pre-dose and 6 hours post-dose, Week 9 pre-dose; Phase 2: Week 1, Week 5, Week 9 pre-dose)
- Phase 1: Overall Response Rate (ORR)(Up to approximately 3 years)
- Phase 1: Major Response Rate (MRR) in participants with Waldenstrom macroglobulinemia (WM)(Up to approximately 3 years)
- Phase 2: Duration of Response (DOR)(Up to approximately 3 years)
- Phase 2: Number of participants with AEs and SAEs(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 2: ORR in participants with R/R MCL as assessed by investigators(Up to approximately 3 years)
- Phase 2: Time to Response (TTR)(Up to approximately 3 years)
- Phase 2: Progression Free Survival (PFS)(Up to approximately 3 years)
- Phase 2: Overall Survival (OS)(Up to approximately 3 years)
- Phase 2: Best Overall Response (BOR) of Partial Response with Lymphocytosis (PR-L) in Participants with R/R CLL/SLL(Up to approximately 3 years)
- Phase 2: Change from baseline in National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index-18 (NFLymSI-18) Disease-related Symptom Physical and Treatment Side Effect Subscales in participants with R/R MCL(Baseline and Day 1 of weeks 5, 13, 25, and 37)
- Phase 2: ORR assessed by the Investigator in participants with R/R CLL/SLL(Up to approximately 3 years)
- Phase 2: Mean change from baseline for the Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu ) questionnaire Physical Well-being and Functional Well-being Subscales for participants with R/R CLL/SLL(Baseline and Day 1 of weeks 5, 13, 25, and 37)