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
Conditions
Keywords
B-cell Malignancy, MZL, FL, DLBCL, Richter's Transformation, CDAC, BTK, degrader, BGB-16673
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
Interventions
DRUGBGB-16673
Orally administered
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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. 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 5. Phase 2: Confirmed diagnosis of MCL, or CLL/SLL 6. 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 ≤ 14 days before the first dose of BGB-16673, or proton-pump inhibitors ≤ 5 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of participants with adverse events (AEs) and serious adverse events (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) | 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 | 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 1a: Maximum tolerated dose (MTD) of BGB-16673 | 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) | 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 2: ORR in participants with R/R Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | ORR is defined as the percentage of participants with partial or complete response, as assessed by the investigator using International Workshop on Chronic Lymphocytic Leukemia (iwCLL), Owen, and Lugano criteria. |
| Phase 1: Major Response Rate (MRR) in participants with Waldenstrom macroglobulinemia (WM) | Up to approximately 3 years | MRR is defined as the percentage of participants who achieved complete response (CR), very good partial response (VGPR), and partial response (PR), as assessed by investigators for participants with WM only. |
| 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 | — |
| Phase 2: ORR in participants with R/R MCL as assessed by investigators | Up to approximately 3 years | ORR is defined as the percentage of participants with partial response or better according to investigators and as determined by Lugano criteria. |
| Phase 2: Duration of Response (DOR) | Up to approximately 3 years | 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. |
| Phase 2: Time to Response (TTR) | Up to approximately 3 years | 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. |
| Phase 2: Progression Free Survival (PFS) | Up to approximately 3 years | 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. |
| Phase 2: Overall Survival (OS) | Up to approximately 3 years | OS is defined as the time from first study drug administration to the date of death due to any cause. |
| 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 | BOR of PR-L or better as determined by IRC and by investigators per iwCLL criteria for CLL and per Lugano criteria for SLL |
| 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 | The NFLymSI-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. A mixed model for repeated measures (MMRM) will be used to estimate the mean change from baseline for NFlymSI-18 subscales of Disease-Related Symptoms Physical (DRSP), and treatment side effects (TSE). |
| Phase 2: ORR assessed by the Investigator in participants with R/R CLL/SLL | Up to approximately 3 years | ORR is defined as the percentage of participants with partial response or better as determined by investigators per iwCLL criteria for CLL and Lugano criteria for SLL. |
| 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 | FACT-Leu is a 44-item patient reported outcome questionnaire with five subscales used to measure health-related quality of life (HRQoL) in leukemia patients. Each question is scored from 0 (not at all) to 4 (very much). |
| 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) | 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). |
| 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 | — |
| 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 | — |
| 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 | — |
Countries
China
Contacts
Primary ContactBeiGene
Outcome results
None listed