B-cell Malignancy, Marginal Zone Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoma, Waldenström Macroglobulinemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Diffuse Large B Cell Lymphoma
Conditions
Brief summary
Study consists of two main parts to explore BGB-16673 recommended dosing, a Phase 1 monotherapy dose finding comprised of monotherapy dose escalation and monotherapy safety expansion of selected doses, and a Phase 2 (expansion cohorts)
Detailed description
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
DRUGBGB-16673
Orally administered
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: 1. Confirmed diagnosis (per World Health Organization (WHO) guidelines, unless otherwise noted) of one of the following: Marginal Zone Lymphoma (MZL), R/R follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), R/R diffuse large B-cell lymphoma (DLBCL), or Richter's transformation to DLBCL. 2. Participants who have previously received a covalently-binding Bruton´s tyrosine kinase (BTK) inhibitor (BTKi) in any line of therapy must have received treatment with the BTK inhibitor for ≥ 8 weeks (unless reason for discontinuation is intolerance). 3. For dose-finding and dose-expansion, participants who had previously received a covalently-binding BTK inhibitor as monotherapy or in combination with other anticancer agents are eligible for the study if they meet any of the following criteria: discontinued the previous BTK inhibitor due to disease progression, experienced disease progression after completing treatment with a BTK inhibitor or discontinued the BTK inhibitor due to toxicity or intolerance. 4. Measurable disease by radiographic assessment or serum IgM level (WM only) 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 6. Participants enrolling in the dose finding phase of the study may be previously treated with a BTKi or may be naïve to BTKi therapy depending on the diagnosis and country of enrollment; participants with MCL enrolling in the expansion cohorts (Phase 2) must have been treated with a BTKi in a prior line of therapy; CLL/SLL participants, in addition to being treated with a BTKi in a prior line of therapy, must also have received a Bcl-2 inhibitor in a prior line of therapy as well (Phase 2).
Exclusion criteria
1. Prior malignancy (other than the disease under study) within the past 2 years, except in situ malignancies that have been curatively resected, localized breast cancer treated with curative intent with no evidence of breast active disease for more than 3 years and receiving adjuvant hormonal therapy, localized Gleason score ≤ 6 prostate cancer undergoing observation or treatment with androgen depravation, or any other cancer treated with curative intent, not on adjuvant treatment, and in the opinion of the investigator is unlikely to recur. 2. Requires ongoing systemic treatment for any other malignancy 3. Requires ongoing systemic (defined as ≥ 10 mg/day of prednisone or equivalent) corticosteroid treatment. 4. Current or history of central nervous system involvement including the brain, spinal cord, leptomeninges, and cerebrospinal fluid (as documented by imaging, cytology, or biopsy) by B-cell malignancy, regardless of whether participants had received treatment for central nervous system disease 5. Known active plasma cell neoplasm, prolymphocytic leukemia, T-cell lymphoma, Burkitt lymphoma, acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, Castleman disease, post-transplant lymphoproliferative disorders, hairy cell leukemia, germinal center B-cell (GCB), DLBCL, EBV+ DLBCL NOS, primary DLBCL of the central nervous system (CNS), primary cutaneous DLBCL - leg type, DLBCL associated with chronic inflammation, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, ALK+ large B-cell lymphoma, primary effusion lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, high-grade B-cell lymphoma - NOS, B-cell lymphoma unclassifiable with features intermediate between DLBCL and classical Hodgkin lymphoma, or history of or currently suspected transformation of an indolent lymphoma to an aggressive histology (except for participants with Richter Transformation to DLBCL are eligible for Part 1a, 1c, or Phase 2 and participants with history of follicular lymphoma transforming to non-GCB DLBCL who are eligible for Part 1a, 1c, or Phase 2). Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants with Adverse Events (AEs) | From the first dose of BGB-16673 until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (Up to 47 weeks) | Number of participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) including results from laboratory assessments, electrocardiograms (ECGs), and physical examinations, and that meet protocol-defined dose-limiting toxicities (DLTs); as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. |
| Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-16673 | Approximately 28 days | MTD is defined as the highest evaluated dose with an estimated toxicity rate closest to the target, while MAD is the highest dose given if MTD is not reached. |
| Phase 1: Recommended dose(s) for Expansion (RDFE) of BGB-16673 | Approximately 3 years | RDFE of BGB-16673 alone will be determined based upon the MTD or MAD. |
| Phase 2: Overall response rate (ORR) | approximately 3 years | Defined as the percentage of participants achieving a best overall response of partial response (PR) or better, assessed by the Independent Review Committee for participants with R/R CLL/SLL and R/R WM (in participants with WM, this is also referred to as major response rate) and by the investigator for other cohorts (R/R MCL, R/R MZL, R/R FL, R/R non-GCB DLBCL, R/R Richter's transformation to DLBCL), evaluated using the Lugano criteria for NHL and SLL, International Workshop of Chronic Lymphocytic Leukemia (iwCLL) criteria for CLL, and the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) criteria for WM. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Single dose and steady-state maximum observed plasma concentration (Cmax) of BGB-16673 | Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose. | — |
| Single dose and steady-state minimum observed plasma concentration (Cmin) of BGB-16673 | Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose. | — |
| Single dose and steady-state time to reach Cmax (tmax) of BGB-16673 | Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose. | — |
| Single dose and steady-state time to reach half of Cmax (T1/2) of BGB-16673 | Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose. | — |
| Single dose and steady-state area under the plasma concentration-time curve (AUC) of BGB-16673 | Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose. | — |
| Single dose and steady-state apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673 | Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose. | — |
| Single dose and steady-state apparent volume of distribution (Vz/F) of BGB-16673 | Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose. | — |
| Single dose and steady-state accumulation ratios of BGB-16673 | Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose. | — |
| Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy | Week 1 Day 1 pre-dose; 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose and 8 hours post-dose; Week 9 Day 1 pre-dose. | — |
| Phase 1: Overall response rate (ORR) | approximately 3 years | Defined as the percentage of participants whose best overall response is partial response or better, as assessed by the investigator and evaluated according to the following criteria: the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for R/R CLL, the International Workshop on Waldenström's Macroglobulinemia (IWWM-11) criteria for R/R WM (in participants with WM, this is also referred to as major response rate), and the Lugano criteria for R/R NHL. |
| Phase 1: Response Rate in Participants with R/R CLL/SLL | approximately 3 years | Defined as the percentage of participants with R/R CLL/SLL whose best overall response is better than stable disease, as determined by investigators. |
| Phase 1: Overall Response Rate in Participants with R/R WM | approximately 3 years | Defined as the percentage of participants with R/R WM who have a response rate of minor response or better. |
| Phase 1: Number of Participants with AEs in part 1e (Japan-only cohort ) | From the first dose of BGB-16673 in Part 1e until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (approximately 3 years) | Number of Japanese participants in Part 1e with TEAEs and SAEs, including results from laboratory assessments, ECGs, and physical examinations, that meet protocol-defined DLTs, graded according to the NCI-CTCAE v5.0. |
| Phase 2: Recommended Phase 2 Dose (RP2D) | approximately 3 years | The Recommended Phase 2 Dose (RP2D) is determined by the sponsor based on the Safety Monitoring Committee's recommendations, taking into account the overall clinical safety, efficacy, pharmacokinetic (PK), and pharmacodynamic data. |
| Phase 2: Number of Participants with AEs | From the first dose of BGB-16673 in Phase 2 until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (approximately 3 years) | Number of participants with TEAEs and SAEs, including results from laboratory assessments, ECGs, and physical examinations, graded according to the NCI-CTCAE v5.0. |
| Phase 2: ORR in Participants with CLL/SLL assessed by investigators | approximately 3 years | Defined as the percentage of participants with CLL/SLL with a best overall response of PR or better, as determined by investigators. |
| Phase 2: Major Response Rate for Participants with WM assessed by investigator | approximately 3 years | Defined as the percentage of participants with WM whose best overall response is PR or better, as determined by investigators using the IWWM-11 criteria. |
| Phase 2: Overall Response Rate for Participants with WM assessed by investigator and IRC | approximately 3 years | Defined as the percentage of participants who achieve at least a minor response (MR) or a more favorable outcome, as assessed by investigators for participants with R/R WM. |
| Phase 2: Rate of Very Good Partial Response (VGPR) or Better in Participants with WM Assessed by Investigator and IRC | approximately 3 years | Defined as the percentage of participants with R/R WM with best response of VGPR or better as determined by IRC and investigator. |
| Phase 2: Response Rate in Participants with R/R CLL/SLL Assessed by Investigator and IRC | approximately 3 years | Defined as the percentage of participants with R/R CLL/SLL whose best overall response is better than stable disease, as determined by IRC and investigator. |
| Phase 2: Duration of Response (DOR) | 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 documented or death, whichever comes first as assessed by the investigator and the IRC. |
| Phase 2: Time to Overall Response (TTOR) | approximately 3 years | TTOR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better), as assessed by IRC and the investigator |
| Phase 2: Time to Major Response (TTMR) in Participants with WM | approximately 3 years | Defined as the time from the date of treatment initiation to the date of first response of PR or better in participants with R/R WM. |
| Phase 2: Time to Response in Participants with R/R CLL/SLL Assessed by Investigator and IRC | approximately 3 years | Defined as the time to first response based on best overall response of better than stable disease, per IRC and investigator. |
| Phase 2: Time to Response in Participants with WM Assessed by Investigator and IRC | approximately 3 years | Defined as the time to first response based on best overall response of minor response or better, per IRC and investigator. |
| Phase 2: Time to Next Treatment (TTNT) | approximately 3 years | Defined as the time from the treatment start date to the initiation of subsequent anticancer therapy. |
| Phase 2: Progression- Free Survival (PFS) | approximately 3 years | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by IRC for R/R CLL/SLL and R/R WM and by the investigator for all participants. |
| Phase 2: Overall Survival (OS) | 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: Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionaire | Baseline and day 1 of Weeks 5, 13, 25, and 37 | Mean change from baseline in the 'physical well-being' and 'functional well-being' subscales of the FACT-Leu for participants with R/R CLL/SLL. FACT-Leu is a 44-item PRO questionnaire with five subscales used to measure health-related quality of life (HRQoL) in leukemia patients. |
| Phase 2: National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 (NFLymSI-18) | Baseline and day 1 of Weeks 5, 13, 25, and 37 | Mean change from baseline in the NFlymSI-18 subscales of disease-related symptoms (DRSP) and 'treatment side effects' for participants with R/R MCL and participants with R/R WM. The NFlymSI-18 is an 18-item patient-reported outcome (PRO) tool specifically designed to assess symptoms and treatment impacts in patients with non-Hodgkin lymphoma. |
Countries
Australia, Brazil, Canada, China, France, Georgia, Germany, Italy, Japan, Moldova, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBeOne Medicines
CONTACTStudy Director, MD
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed