A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies
- Conditions
- Marginal Zone LymphomaChronic Lymphocytic LeukemiaDiffuse Large B Cell LymphomaB-cell MalignancySmall Lymphocytic LymphomaFollicular LymphomaWaldenström MacroglobulinemiaNon-Hodgkin LymphomaMantle Cell Lymphoma
- Interventions
- Registration Number
- NCT05006716
- Lead Sponsor
- BeiGene
- 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
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 621
Not provided
- 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.
- Requires ongoing systemic treatment for any other malignancy
- Requires ongoing systemic (defined as ≥ 10 mg/day of prednisone or equivalent) corticosteroid treatment.
- 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
- 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/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase 2 (Monotherapy Expansion) BGB-16673 Cohorts of participants with R/R CLL/SLL, R/R MCL, R/R WM, R/R MZL, R/R FL, R/R RT, and R/R DLBCL will be enrolled to recieve the RDFE(s) identified in Phase 1 to further evaluate the safety and efficacy of BGB-16673. Part 1e (Japan-only Cohort) BGB-16673 Japanese participants with R/R MZL, FL, MCL, CLL/SLL, and WM will be enrolled at selected RDFE(s) to assess the safety and tolerability of BGB-16673. Part 1f (Additional Monotherapy Safety Expansion in BTKi Naive B-Cell Malignancies) BGB-16673 Participants with CLL/SLL, MCL, WM, MZL, or Richter's transformation to DLBCL who have not received a prior BTKi (either covalent or noncovalent) will be enrolled at selected dose levels. Part 1a (Monotherapy Dose Escalation) BGB-16673 Dose escalation in specific subtypes of non-Hodgkin lymphoma (NHL), including relapsed or refractory (R/R) marginal zone lymphoma (MZL), relapsed or refractory (R/R) follicular lymphoma (FL) Grades 1, 2, and 3a, relapsed or refractory (R/R) mantle cell lymphoma (MCL), relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), relapsed or refractory (R/R) Richter's transformation (RT), and relapsed or refractory (R/R) Waldenström macroglobulinemia (WM), to evaluate the safety and tolerability of BGB-16673. Part 1b (Monotherapy Safety Expansion) BGB-16673 Participants with R/R MZL, MCL, CLL/SLL, and WM will be enrolled at selected doses to help determine the recommended dose(s) for expansion (RDFE(s)) for BGB-16673. Part 1c (Additional Monotherapy Safety Expansion) BGB-16673 Additional safety data will be collected from participants with R/R MZL, WM, RT, DLBCL, or FL to confirm the RDFE(s) of BGB-16673 for those with non-CLL/SLL/MCL histologies. Part 1d (Additional Monotherapy Safety Expansion in R/R CLL/SLL) BGB-16673 Participants with R/R CLL/SLL will be enrolled at selected RDFE(s) to generate additional safety and efficacy data for BGB-16673.
- Primary Outcome Measures
Name Time Method 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 28 days 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 MCL and by the investigator for other cohorts (R/R WM, R/R FL, R/R non-GCB DLBCL, R/R Ritchter's transformation to DLBCL), evaluated using the Lugano criteria for NHL and SLL, iwCLL criteria for CLL, and IWWM-6 criteria for WM.
- Secondary Outcome Measures
Name Time Method 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 better than stable disease, 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-6) criteria for R/R WM, and the Lugano criteria for R/R NHL.
Phase 1: Number of R/R WM Participants with major response rate (MRR) approximately 3 years MRR is defined as the percentage of participants whose best overall response (BOR) is partial response (PR) or better (PR, very good partial response (VGPR), or complete response (CR)) as assessed by the investigator and evaluated per the IWWM-6 criteria.
Phase 2: Response rate of minor response or better 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 cohort 3 (R/R WM)
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 Response (TTR) 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 assessed by IRC and the investigator
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 Defined as the dose of a drug recommended for use in Phase 2 clinical trials, 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, that meet protocol-defined DLTs, graded according to the NCI-CTCAE v5.0.
Phase 2: Complete Response Rate (CRR) approximately 3 years CRR for participants in Cohort 2 (R/R blastoid or nonblastoid variant R/R MCL) is defined as the percentage of participants who achieve a complete response (CR), as determined by both the Independent Review Committee (IRC) and investigators.
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 and the investigator
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 Cohort 1 participants (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 Cohort 2 participants (R/R MCL). 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.
Trial Locations
- Locations (117)
University of Alabama At Birmingham Hospital
🇺🇸Birmingham, Alabama, United States
Western Regional Medical Center, Llc
🇺🇸Goodyear, Arizona, United States
Mayo Clinic Phoenix
🇺🇸Phoenix, Arizona, United States
Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University of California San Diego (Ucsd) Moores Cancer Center
🇺🇸La Jolla, California, United States
Stanford Medicine
🇺🇸Palo Alto, California, United States
UCLA Santa Monica Cancer Care
🇺🇸Santa Monica, California, United States
Uchealth North
🇺🇸Fort Collins, Colorado, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Scroll for more (107 remaining)University of Alabama At Birmingham Hospital🇺🇸Birmingham, Alabama, United States