John Pagel, MD, PhD, Discusses Key Takeaways of a Trial Examining Zanubrutinib Plus Zandelisib in B-Cell Malignancies


The combination of zanubrutinib and zandelisib for the treatment of B-cell malignancies may offer patients the opportunity to receive therapy that is not based around chemotherapy.

John Pagel, MD, PhD, from the Swedish Cancer Institute, spoke about the combination of zandelisib and zanubrutinib (Brukinsa), in a phase 1 trial (NCT02914938) and how the combination allows patients a chemotherapy-free alternative. Additionally, investigators are creating expansion cohorts to test the combination in other types of B-cell malignancies. Pagel hopes to see this research carried forward to phase 2 or phase 3 trials.


The important key takeaway of this trial is that we now have the opportunity to use a very important class of drugs—such as a PI3K inhibitor which is very well tolerated towards adverse events—and that’s critically important. This is a class of drugs that has not been widely utilized because of the adverse event profile, but [this concern] is largely mitigated because of this novel intermittent schedule of using zandelisib combined [with] zanubrutinib, which is another very well tolerated therapy. What’s important is that we’re providing opportunities for patients to get therapies that are chemotherapy free that will continue to benefit them, hopefully for long periods of time. It’s a relatively small number of patients at this point with relatively short follow-up, but it does suggest to us that this will be a regimen that patients can use in the future.

Currently, we’re enrolling expansion cohorts for follicular lymphoma and mantle cell lymphoma. [We will be using the same doses from the first trial] and using this intermittent schedule of zandelisib, so we’ll see what those data show. ‘'m very confident that this will lead to further investigation, and it will almost assuredly warrant phase 2 and hopefully subsequently phase 3 investigations.


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. 39 (supply15): 7553. doi: 10.1200/JCO.2021.39.15_suppl.7553

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