Study Evaluating the Efficacy and Tolerance of a Zanubrutinib and BGB-11417 Combination in Patients Previously Treated for Waldenström Macroglobulinemia

study design : Open label, multicenter phase 2 trial

population : Patients with previously treated Waldenstrom macroglobulinemia

Primary objective :

To evaluate the efficacy of a combination of zanubrutinib and BGB-11417 given for a limited duration of time in Refractory/Relapsing (R/R) WM by the proportion of subjects achieving either a Complete Response (CR) or Very Good Partial Responses (VGPR).duration of time in Refractory/relapsing (R/R) Waldenstrom macroglobulinemia (WM)

Secondary objectives:

* To further evaluate the efficacy of a combination of zanubrutinib and BGB-11417 given for a limited duration of time in R/R WM * To determine the incidence and severity of serum M-protein (monoclonal IgM) rebound after planned cessation of the combination of zanubrutinib and BGB-11417-101 in R/R WM * To evaluate the safety and tolerability of a combination of zanubrutinib and BGB-11417 given for a limited duration of time in R/R WM

Sample size : 102 patients Length of study: Inclusion period: 24 months Treatment duration: 18 months (twenty 28-days cycles) Follow-up period: 3 years

Study treatment :

The investigational medicinal products (IMP) are Zanubrutinib (BGB- 3111) and BGB-11417.Treatment will be administered for a total of twenty 28 day cycles:

* Cycle 1 with zanubrutinib only * Cycle 2 with zanubrutinib plus BGB-11417 ramp-up * Cycle 2 with zanubrutinib plus BGB-11417 ramp-up

\*cycle 2, day 1 : 10mg * cycle 2, day 2 : 20 mg * cycle 2, day 3 : 40mg * cycle 2, day 4-7 : 80md daily * cycle 2, day 8 and beyond : 160 mg daily * Cycles 3-20 with zanubrutinib plus BGB-11417 full dose

All patient will receive both drugs.

Study procedures:

Screening period:

Assessments may be done up to 28 days before the treatment start and will include:

Clinical assessments