ICML 2023 | SWOG 2207: zanubrutinib or tazemetostat plus tafa-len in transplant-ineligible R/R DLBCL

As part of the SWOG/NCI Cooperative Group network, we are interested in trying to improve therapies for patients who are frail, who might not be able to undergo intense treatment strategies such as CAR-T or even bispecifics, who have relapsed/refractory diffuse large B-cell lymphoma. So one of the things that we’ve been working on and we’re hoping this trial gets activated in the next month or so, is working to build on the tafasitamab-lenalidomide backbone, since that’s been highly effective and very well tolerated for patients with diffuse large B-cell lymphoma. And our strategy right now is to combine some biologically targeted agents to this backbone. This backbone, though very effective, really is not geared toward any specific biologic subtypes of diffuse large B-cell lymphoma. So we are randomizing patients to tafasitamab-lenalidomide plus or minus zanubrutinib, a BTK inhibitor, plus or minus tazemetostat an EZH2 inhibitor. And at this point we are not stratifying for cell of origin for diffuse large B-cell lymphoma. So patients will be able to be randomized regardless of cell of origin. But we are going to look at cell of origin and see if that makes a difference in terms of their outcome with each of these targeted agents. And the hope is that sort of the ABC subtype, if you will, would be more responsive to the BTK inhibitor, whereas the GCB subtype might be more sensitive to the EZH2 inhibitor. So we’re very excited for this. We’re going to be conducting patient reported outcomes as well to see if we can improve quality of life and sort of prolong time in which patients can feel active and have their treatment really just controlled. Although our primary endpoint is progression-free survival, our goal is really we know in this… is not curative when we’re using these types of treatments, but to really improve quality of life for an extended period of time and to not rely on such intensive therapies. In addition, intensive therapies are pretty challenging to use in the community setting. So we recognize that there are a lot of community settings patients can’t receive CAR-T and even bispecifics in the first month during sort of ramp up phase, there’s a high risk for CRS and admissions to ICUs. And so there’s a lot of trepidation about using those types of intensive therapies in the community setting. So we hope that this would offer an alternative to patients who are frail or patients who might live in remote areas that might not be able to get to a large sort of academic institute where they can undergo more intensive treatment. So we’re excited about this study. It will be open across the Co-operative Group Networks in the United States, and we’re hoping that many sites will participate in accruing patients to this.