Clinical Trial 23454

• Overview

  Study Title:

  A Phase 1b/2, Open-Label, Dose Finding and Expansion Study of BGB-16673 in Combination with Other Agents in Relapsed or Refractory B-Cell Malignancies

  Objective:

  Primary Objectives: Part 1a (Dose Escalation): To evaluate safety and tolerability of and identify the recommended dose(s) for expansion (RDFE[s]) for BGB-16673 combination treatments in patients with relapsed/refractory (R/R) B-cell malignancies. Part 1b (Safety Expansion): To characterize the safety and tolerability of BGB-16673 combination treatments at the RDFE(s) in patients with R/R B-cell malignancies. Secondary Objectives: Part 1a (Dose Escalation) and Part 1b (Safety Expansion): To assess the preliminary antitumor activity of BGB-16673 combination treatments at the RDFE(s) in patients with R/R B-cell malignancies. To assess the pharmacokinetics (PK) for BGB-16673 and other study drugs in combination treatments. Substudy 1 Part 1b only: To assess undetectable minimal residual disease (uMRD) in patients with CLL/SLL during and after treatment with BGB-16673 and sonrotoclax.

• Treatments

  Therapies:

  Immunotherapy; Therapy (NOS); Tyrosine Kinase Inhibitor

  Medications:

  BGB-16673 (); Glofitamab (); Mosunetuzumab (); Sonrotoclax (); Zanubrutinib ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Patients (or legal representative[s] where permitted; see Section 10.3.1 for details) must sign the ICF and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
  • Patients must be ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the informed consent.
  • Patients have confirmed diagnosis (per WHO guidelines, unless otherwise noted) of a R/R B-cell malignancy as defined in the protocol.
  • Patients must have measurable disease as defined in the protocol.
  • Patients with CLL/SLL must agree to collection of bone marrow samples (FFPE block or approximately 15 freshly cut unstained FFPE slides and bone marrow biopsy).
  • Patient has a life expectancy of > 6 months.
  • Patients must have a stable ECOG Performance Status of 0 to 2.
  • Patients must have adequate organ function as indicated by the protocol.
  • Other inclusion criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Patients with treatment-naive B-cell malignancies.
  • Patients who are unable to comply with the requirements of the protocol unless the written approval of the medical monitor has been obtained before informed consent.
  • Patients with active leptomeningeal disease or uncontrolled, untreated brain metastasis.
  • Patients with any malignancy ≤ 2 years before first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer).
  • Autologous stem cell transplant ≤ 3 months prior to screening or chimeric antigen T-cell therapy ≤ 3 months prior to screening.
  • Prior allogeneic stem cell transplant with active GVHD, or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent.
  • Patients with active HBV by presence of HBcAb and HBsAg. Patients with presence of HBcAb, but absence of HBsAg, are eligible if HBV DNA is undetectable (Note: The limit of detection for HBV DNA must have a sensitivity of > Patients with active hepatitis C. Note: Patients with a negative HCV antibody test at screening, or positive HCV antibody test and undetectable HCV RNA at screening (Note: The limit of detection for HCV RNA must have a sensitivity of > Patients with untreated HIV infection, if known.
  • Patients who have symptomatic COVID-19 infection.
  • Active fungal, bacterial, and/or viral infection requiring systemic therapy.
  • Patients with any major surgical procedure ≤ 28 days before first dose of study treatment. Patients must have recovered adequately from the procedure and/or complications from the procedure before first dose of study treatment.
  • Chronic respiratory disease that requires continuous oxygen; history of significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, or cardiovascular disease; or any other medical condition that, in the opinion of the investigator, would adversely affect his/her participation in this study.
  • Patients with any of the following cardiovascular risk factors outlined in the protocol.
  • Patients with QTcF > 480 ms (average of triplicate readings) or a history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, or family history of Long QT Syndrome).
  • Patients with toxicities because of prior anticancer therapy that have not recovered to ≤ Grade 1 or stabilized, except for adverse events not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities such as anemia, neutropenia, and thrombocytopenia).
  • Patients who are treated with a moderate or strong CYP3A inhibitor (7 days or 5 half lives, whichever is longer) or moderate or strong CYP3A inducer (14 days or 5 half-lives, whichever is longer) before the first dose of study treatment or who require ongoing treatment with a moderate or strong CYP3A inhibitor or a strong CYP3A inducer.
  • Patients who were administered a live vaccine ≤ 35 days before first dose of study drug/treatment. NOTE: Vaccines for COVID-19 are allowed except for any live vaccine that may become available. Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
  • Other exclusion criteria may apply.

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