A Phase I/II, Open-Label, Dose-Escalation and -Expansion Study of the Bruton Tyrosine Kinase Targeted Protein Degrader BGB-16673 in Patients With B-Cell Malignancies
Study Identifier:
BGB-16673-101
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Recruiting
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Study Summary
To study Bruton Tyrosine Kinase-Targeted Protein-Degrader BGB-16673 in Patients With B-Cell Malignancies
To explore BGB-16673 recommended dosing, a part 1 monotherapy dose finding and a part 2 (cohort expansion in two cohorts)
To evaluate the safety, tolerability, PK, PD, and anti-tumor activity under the RP2D in pts with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL). Additional efficacy analyses will include progression-free survival and overall survival. Safety was assessed per CTCAE v5.0 and iwCLL hematologic toxicity criteria. Dose-limiting toxicities (DLTs) were assessed in the first 4 weeks (cycle 1). Response was assessed per iwCLL 2018 criteria (or Cheson et al, 2014 for SLL), with first assessment after 12 weeks of treatment.
To update the results in patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL) enrolled in the phase 1 portion To evaluate safety and efficacy of BGB-16673 in pts with WM in the phase 1 portion of the study.
To evaluate BGB-16673 monotherapy in patients (pts) with a range of B-cell malignancies.
This study is designed to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of BGB-16673 in patients with B-cell malignancies and to determine the Extended Recommended Dose (RDFE) and Phase 2 Recommended Dose (RP2D).
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
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. 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). Eligible patients had R/R NHL (≥2 prior therapies), an ECOG performance status of 0-2, and adequate organ function. Patients with MZL must have previously received an anti-CD20 antibody in the EU and both an anti-CD20 antibody and a cBTKi in the US. Eligible patients must have confirmed R/R WM (≥2 prior therapies), an ECOG performance status of 0-2, and adequate organ function. Patients must have previously received an anti-CD20 antibody and, in the US and EU, a covalent BTK inhibitor (cBTKi). Eligible pts must have confirmed R/R WM (≥2 prior therapies), an ECOG performance status of 0-2, previous receipt of an anti-CD20 antibody, and, in the US/EU, a covalent BTK inhibitor (cBTKi). Eligible pts must have confirmed R/R CLL/SLL (≥2 prior therapies), an ECOG performance status of 0-2, and adequate organ function. In the US/EU/Australia, pts must have previously received a covalent BTKi (cBTKi).
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).
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Daniel Morillo Giles
Status
Recruiting
Condition(s) Treated at Site
Hematological Cancer
Lymphoma
Waldenstrom Macroglobulinemia
Leukemia