Recruiting NCT05006716

A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies

Phase I / Phase II Interventional B-cell Malignancy Marginal Zone Lymphoma Follicular Lymphoma Non-Hodgkin Lymphoma

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: BGB-16673.
Who it may be relevant to: Registry conditions: B-cell Malignancy, Marginal Zone Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoma. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Brazil, Canada, China +11
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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

Drug BGB-16673
Orally administered

Primary outcome measures

Phase 1: Number of Participants with Adverse Events (AEs) [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 [Time frame: Approximately 28 days]
Phase 1: Recommended dose(s) for Expansion (RDFE) of BGB-16673 [Time frame: Approximately 3 years]
Phase 2: Overall response rate (ORR) [Time frame: approximately 3 years]

Secondary outcome measures (12)

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]

Eligibility criteria

Inclusion criteria

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.
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).
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.
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.
Measurable disease by radiographic assessment or serum IgM level (WM only)
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Single group
Masking: Open label
Primary purpose: Treatment

Study locations

United States · 31 centers

University of Alabama At Birmingham Hospital — Birmingham
Mayo Clinic Phoenix — Phoenix
Honor Health Research Institute — Scottsdale
University of Arizona Cancer Center — Tucson
University of California San Diego (Ucsd) Moores Cancer Center — La Jolla
Stanford Medicine — Palo Alto
UCLA Santa Monica Cancer Care — Santa Monica
Uchealth North — Fort Collins
… and 23 more centers

Australia · 9 centers

Concord Repatriation General Hospital — Concord
Calvary Mater Newcastle — Waratah
Princess Alexandra Hospital — Woolloongabba
St Vincents Hospital Melbourne — Fitzroy
Austin Health — Heidelberg
Peter Maccallum Cancer Centre — Melbourne
The Alfred Hospital — Melbourne
Linear Clinical Research — Nedlands
… and 1 more center

France · 9 centers

Centre de Lutte Contre Le Cancer Institut Bergonie — Bordeaux
Hopital Estaing — ClermontFerrand
Chu Henri Mondor — Créteil
Hopital Claude Huriez Chu Lille — Lille
Centre Leon Berard — Lyon
Institut Paoli Calmettes — Marseille
Chu Montpellier Hopital Saint Eloi — Montpellier
Hopital de La Pitie Salpetriere — Paris
… and 1 more center

Brazil · 7 centers

Hospital Sirio Libanes Brasilia — Brasília
Hospital Erasto Gaertner — Curitiba
Centro Gaucho Integrado de Oncologia Hospital Mae de Deus — Porto Alegre
Real E Benemerita Associacao Portuguesa de Sao Paulo — São Paulo
Instituto Dor de Pesquisa E Ensino Sao Paulo — São Paulo
Hospital Nove de Julho Dasa — São Paulo
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein — São Paulo

China · 7 centers

Peking Union Medical College Hospital — Beijing
Nanfang Hospital, Southern Medical University — Guangzhou
Henan Cancer Hospital — Zhengzhou
Yichang Central Peoples Hospitaljiangnan Branch — Yichang
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine — Shanghai
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciencestu — Tianjin
The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Germany · 7 centers

Uniklinik Koeln (Aoer) — Cologne
Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden — Dresden
Universitares Krebszentrum Leipzig — Leipzig
Universitaetsklinikum Schleswig Holstein Campus Luebeck — Lübeck
Klinikum Johannes Gutenberg Universitaet Mainz — Mainz
Klinikum Grosshadern Ludwig Maximilians Universitat Munchen — München
Universitaetsklinikum Ulm — Ulm

South Korea · 7 centers