study of bcl-2 inhibitor sonrotoclax (bgb-11417) in participants with mature b-cell malignancies

Conditions: Mature B-Cell Malignancies

Summary: the purpose of this study is to determine the safety, tolerability; and to define the maximum tolerated dose (mtd) and recommended phase 2 dose (rp2d); and to evaluate the safety and tolerability of the ramp-up dosing schedule and at the rp2d of bgb-11417 monotherapy, and when given in combination with zanubrutinib and obinutuzumab.


Eligibility criteria:
key inclusion criteria: * confirmed diagnosis of one of the following: nhl cohorts: 1. mzl i. r/r extranodal, splenic, or nodal mzl defined as disease that relapsed after, or was refractory to, at least one prior therapy ii. active disease requiring treatment 2. fl i. r/r fl (grade 1, 2 or 3a based on the who 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy 3. dlbcl i. r/r dlbcl (including all subtypes of dlbcl) defined as disease that relapsed after, or was refractory to, at least two prior systemic therapies and has either progressed following or is not a candidate for autologous stem cell transplant (due to comorbidities or non-responsiveness to salvage chemotherapy) 4. transformed indolent b-cell nhl i. any lymphoma otherwise eligible for part 1 that has transformed into a more aggressive lymphoma. patients with transformation from cll or sll (richter's transformation) are not eligible for part 1 cll/sll cohorts: 5. cll/sll diagnosis that meets the international workshop on chronic lymphocytic leukemia (iwcll) criteria i. disease characterized as treatment naive (tn) or r/r disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy ii. requiring treatment as defined by history mcl cohorts: 6. who-defined mcl i. r/r mcl defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy; ii. requiring treatment in the opinion of the investigator wm cohorts: g. who-defined wm (clinical and definitive histologic diagnosis) i. r/r disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy; ii. meeting at least 1 criterion for treatment according to consensus panel criteria from the seventh international workshop on waldenström's macroglobulinemia (dimopoulos et al 2014) * measurable disease by computed tomography (ct)/magnetic resonance imaging (mri), defined as: 1. cll: at least 1 lymph node \> 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes measured by flow cytometry 2. dlbcl, fl, mzl, mcl, or sll: at least 1 lymph node \> 1.5 cm in longest diameter or 1 extranodal lesion \> 1.0 cm in the longest diameter, measurable in at least 2 perpendicular dimensions. for mzl, isolated splenomegaly is considered measurable for this study 3. wm: serum immunoglobulin (ig) m level \> 0.5 g/dl * eastern cooperative oncology group (ecog) performance status of 0 to 2 * adequate organ function * adequate pancreatic function indicated by: 1. serum amylase ≤ 1.5 x upper limit of normal (uln) 2. serum lipase ≤ 1.5 x uln key exclusion criteria: * known current central nervous system involvement by lymphoma/leukemia * known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected richter's syndrome * prior therapy ≥ 2 months with or progression on a b-cell lymphoma-2 (bcl-2) inhibitor note: other protocol defined inclusion/exclusion criteria may apply.

Keywords: nhl bcl2 inhibitor cll mcl mzl sll wm bcl-2i btki