Patients with relapsed/refractory B-cell malignancies may potentially benefit from the combination of zandelisib and zanubrutinib.
John Pagel, MD, PhD, from the Swedish Cancer Institute, spoke about topline results from a phase 1 trial (NCT02914938) involving the combination of zanubrutinib (Brukinsa) and zandelisib for relapsed/refractory B-cell malignancies, with the goal of treatment being to overcome monotherapy resistance.
This is an important and interesting trial using 2 novel oral targeted therapies, 1 known as zanubrutinib, which is an oral Bruton tyrosine kinase inhibitor, and a second known as zandelisib, previously known as ME-401, which is another oral agent that targets a different pathway inside a B-lymphocyte, PI3K. This drug is selective for the d isoform of PI3K. The trial is very important because these 2 drugs have synergistic activity and cell lines, even at sub-optimal concentrations. The goal would be that we could overcome existing or acquired monotherapy resistance by using these 2 drugs in combination. Moreover, this important trial aims to study an innovative dose schedule to improve the tolerability of the combination treatment, to provide a deeper response to therapy, and to do that in a finite fashion with 2 years of treatment for relapsed patients with B- cell malignancies.
This is a trial for patients who have failed at least 1 prior therapy and for patients with indolent B-cell malignancies such as follicular lymphoma, mantle cell lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, and chronic lymphocytic leukemia. The trial uses these 2 different drugs with a very interesting schedule. The zandelisib, or the PI3K inhibitor, is delivered as an oral agent at 60 mg daily. This novel schedule uses daily dosing for 7 days of each 28-day cycle beginning from the very first cycle of the regimen. So simply [put], patients receive 7 days of [zandelisib] with 3 weeks off the drug [and this continues] every 28 days. During that cycle, zanubrutinib is delivered at 80 mg given twice a day as an oral agent and it’s delivered daily throughout the 28-day cycle.
Soumerai J, Jagadeesh D, Salman H, et al. Initial results of the combination of PI3Kδ inhibitor zandelisib (ME-401) and the BTK inhibitor zanubrutinib in patients (pts) with relapsed or refractory (R/R) B-cell malignancies. J Clin Oncol. 2021;39(suppl 15):7553. doi: 10.1200/JCO.2021.39.15_suppl.7553