A Phase 1, Open-Label, Dose-Escalation and -Expansion Study of the Bruton Tyrosine Kinase-Targeted Protein-Degrader BGB-16673 in Patients With B-Cell Malignancies
Professor Chan Cheah
- B-cell Malignancy
- Marginal Zone Lymphoma
- Follicular Lymphoma
- Non-hodgkin Lymphoma
- Waldenström Macroglobulinemia
Study consists of two parts to explore BGB-16673 recommended dosing, a part 1 monotherapy dose finding and a part 2 (cohort expansion in two cohorts)
- Provision of signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection
- Age ≥ 18 years
- Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of one of the following: MZL, FL, MCL, CLL/SLL, or WM.
- Patients who have previously received a BTK inhibitor in any line of therapy must have received only 1 BTK inhibitor-containing regimen and must have received treatment with the BTK inhibitor for ≥ 8 weeks. Patients may have received treatment with 2 different BTKi if the initial BTKi was discontinued secondary to treatment-emergent toxicity.
- For dose-finding and dose-expansion, patients who had previously received a 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)
- ECOG Performance Status of 0 to 2
- Patients enrolling in the dose finding phase of the study may be previously treated with a BTKi or may be naïve to BTKi therapy; patients with CLL/SLL or MCL enrolling in the expansion cohorts must have been treated with a BTKi in a prior line of therapy.
- Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score = 6 prostate cancer
- 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 patient had received treatment for central nervous system disease
- Known active plasma cell neoplasm, prolymphocytic leukemia, blastoid-variant MCL, T-cell lymphoma, Burkitt lymphoma, acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, Castleman disease, post-transplant lymphoproliferative disorders, hairy cell leukemia, or
- Note: Other protocol defined Inclusion