Clinical Trial 24234

• Overview

  Study 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

  Summary:

  This study consists of two parts: dose escalation and dose expansion. During the dose escalation part, the study doctors will test different doses of the study drug to find the recommended dose that people can take without having serious side effects. During the dose expansion part, the study doctors will test the study drug in a larger number of people using the dose or doses identified from dose escalation. The study is open label, which means that the participants and the study doctors will know what treatment is received.

  Objective:

  Primary Objective: To evaluate the safety and tolerability of BGB-16673 monotherapy. To define the maximum tolerated dose (MTD) (or maximum assessed dose [MAD]) and the recommended dose(s) for expansion (RDFE[s]) of BGB-16673. Secondary Objectives: To characterize the PK profile of BGB-16673 as monotherapy. To characterize the pharmacodynamic profile of BGB-16673 in peripheral blood. To characterize the preliminary antitumor activity of BGB-16673 monotherapy. To assess the safety and tolerability of BGB-16673 in Japanese patients. To characterize the PK of BGB-16673 in Japanese patients. To assess the preliminary antitumor activity of BGB-16673 in Japanese patients.

• Treatments

  Therapies:

  Bruton Tyrosine Kinase-Targeted Protein-Degrader

  Medications:

  BGB-16673 ()

• Inclusion 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.
  • 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).
  • Other criteria may apply

• Exclusion Criteria

  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).
  • Other exclusions may apply

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