RecruitingInterventionalPhase 1/Phase 2

A Phase 1/2, Open-Label, Dose-Escalation and -Expansion Study of the Bruton Tyrosine Kinase Targeted Protein Degrader BGB-16673 in Patients With B-Cell Malignancies

NCT ID: NCT05006716Sponsor: BeOne MedicinesLast updated: 2026-06-18

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.

Arms & interventions

DrugBGB-16673
Orally administered

Outcome measures

Primary

Phase 1: Number of Participants with Adverse Events (AEs)
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.
Time frame: 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)
Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-16673
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.
Time frame: Approximately 28 days
Phase 1: Recommended dose(s) for Expansion (RDFE) of BGB-16673
RDFE of BGB-16673 alone will be determined based upon the MTD or MAD.
Time frame: Approximately 3 years
Phase 2: Overall response rate (ORR)
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.
Time frame: approximately 3 years

Secondary

Single dose and steady-state maximum observed plasma concentration (Cmax) of BGB-16673
Time frame: 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
Time frame: 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
Time frame: 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 elimination half-life (T1/2) of BGB-16673
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: approximately 3 years
Phase 1: Response Rate in Participants with R/R CLL/SLL
Time frame: approximately 3 years
Phase 1: Overall Response Rate in Participants with R/R WM
Time frame: approximately 3 years
Phase 1: Number of Participants with AEs in part 1e (Japan-only cohort)
Time frame: 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)
Phase 2: Recommended Phase 2 Dose (RP2D)
Time frame: approximately 3 years
Phase 2: Number of Participants with AEs
Time frame: 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)
Phase 2: ORR in Participants with CLL/SLL assessed by investigators
Time frame: approximately 3 years
Phase 2: Major Response Rate for Participants with WM assessed by investigator
Time frame: approximately 3 years
Phase 2: Overall Response Rate for Participants with WM assessed by investigator and IRC
Time frame: approximately 3 years
Phase 2: Rate of Very Good Partial Response (VGPR) or Better in Participants with WM Assessed by Investigator and IRC
Time frame: approximately 3 years
Phase 2: Response Rate in Participants with R/R CLL/SLL Assessed by Investigator and IRC
Time frame: approximately 3 years
Phase 2: Duration of Response (DOR)
Time frame: approximately 3 years
Phase 2: Time to Overall Response (TTOR)
Time frame: approximately 3 years
Phase 2: Time to Major Response (TTMR) in Participants with WM
Time frame: approximately 3 years
Phase 2: Time to Response in Participants with R/R CLL/SLL Assessed by Investigator and IRC
Time frame: approximately 3 years
Phase 2: Time to Response in Participants with WM Assessed by Investigator and IRC
Time frame: approximately 3 years
Phase 2: Time to Next Treatment (TTNT)
Time frame: approximately 3 years
Phase 2: Progression- Free Survival (PFS)
Time frame: approximately 3 years
Phase 2: Overall Survival (OS)
Time frame: approximately 3 years
Phase 2: Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire
Time frame: Baseline and day 1 of Weeks 5, 13, 25, and 37
Phase 2: National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 (NFLymSI-18)
Time frame: Baseline and day 1 of Weeks 5, 13, 25, and 37

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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. Phase 2 Cohorts in R/R CLL/SLL, R/R MCL, and R/R WM only: Participants who previously received a BTKi are eligible if they had disease progression on only one regimen containing a covalent BTKi. Note: Participants may have received treatment with ≥ 2 different covalent BTKis if additional BTKis were discontinued secondary to an event other than disease progression. 5. Measurable disease by radiographic assessment or serum IgM level (WM only) 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 7. 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/Exclusion criteria may apply.

Study locations (31)

University of Alabama At Birmingham Hospital

Birmingham, Alabama, 35294-0004

Recruiting

Mayo Clinic Phoenix

Phoenix, Arizona, 85054-4502

Completed

Honor Health Research Institute

Scottsdale, Arizona, 85258-4566

Recruiting

University of Arizona Cancer Center

Tucson, Arizona, 85724-0001

Recruiting

University of California San Diego (Ucsd) Moores Cancer Center

La Jolla, California, 92093-1503

Recruiting

Stanford Medicine

Palo Alto, California, 94304-2205

Recruiting

UCLA Santa Monica Cancer Care

Santa Monica, California, 90404-2023

Recruiting

Uchealth North

Fort Collins, Colorado, 80528-3413

Recruiting

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224-1865

Recruiting

Mount Sinai Medical Center Braman Comprehensive Cancer Center

Miami, Florida, 33140

Recruiting

Tampa General Hospital Cancer Institute

Tampa, Florida, 33606-3571

Recruiting

Augusta University

Augusta, Georgia, 30912-0002

Recruiting

Southeastern Regional Medical Center

Newnan, Georgia, 30265-8001

Recruiting

Midwestern Regional Medical Center

Zion, Illinois, 60099-2676

Completed

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242-1009

Recruiting

Norton Cancer Institute Pavilion

Louisville, Kentucky, 40207-4700

Active Not Recruiting

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809-3738

Recruiting

American Oncology Partners of Maryland Pa

Bethesda, Maryland, 20817-7847

Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, 02215-5418

Recruiting

Karmanos Cancer Institute

Detroit, Michigan, 48201-2013

Recruiting

Mayo Clinic Rochester

Rochester, Minnesota, 55905-0001

Recruiting

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169-3321

Recruiting

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203

Recruiting

Columbia University Medical Center

New York, New York, 10032

Recruiting

Weill Cornell Medical College Newyork Presbyterian Hospital

New York, New York, 10065-4870

Recruiting

Memorial Sloan Kettering Cancer Center Mskcc

New York, New York, 10065-6800

Recruiting

Tennesse Oncology Chattanooga Downtown

Chattanooga, Tennessee, 37404

Recruiting

Tennessee Oncology, Pllc Nashville

Nashville, Tennessee, 37203

Recruiting

Md Anderson Cancer Center

Houston, Texas, 77030-3907

Recruiting

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298

Recruiting

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-4433

Recruiting