S2207: RANDOMIZED PHASE II STUDY OF THE ADDITION OF TARGETED AGENTS TO TAFASITAMAB‐LENALIDOMIDE IN TRANSPLANT INELIGIBLE PATIENTS WITH RELAPSED/REFRACTORY LBCL

Abstract

Large B-cell lymphoma (LBCL) is the most common lymphoma worldwide. About 40% of patients relapse, and most are not eligible for transplantation due to chemoresistant disease, advanced age, comorbidities, or lack of access to tertiary care. Similarly, CAR-T remains inaccessible for the majority of patients due to poor fitness, aggressive disease, lack of social support, to name a few. Thus, R/R LBCL is an area of great unmet need, with median survival measuring <1 yr. Recently, several less intensive regimens designed for outpatient administration have been approved in the United States. Tafasitamab-lenalidomide is a promising regimen, with durable remissions comparable even to CAR T-cell in some analyses. We hypothesize that if tafa-len is a well-tolerated and effective backbone, then the addition of biologically targeted agents could lead to improved outcomes while limiting toxicity. The SWOG 2207 trial will test the addition of tazemetostat or zanubrutinib to the tafa-len backbone in a randomized study open nationwide. Furthermore, we will evaluate the impact of cell-of-origin (COO) on efficacy. Following a safety run-in of 12 patients per each experimental arm, the randomized Phase II study will enroll 180 patients to Arm 1: tafa-len + tazemetostat; Arm 2: tafa-len (control); or Arm 3: tafa-len + zanubrutinib (Figure 1). The primary objective of the phase II portion is to compare the PFS of patients treated on the experimental arms with the control. Secondary objectives will include estimating hazard ratios for PFS based on GCB and non-GCB subtypes for each experimental treatment arm. Other objectives will include exploring PFS by molecular profile and genetic subtypes. Frailty and its correlation to outcome will be assessed. In addition, patient-reported lymphoma specific symptoms by PRO-CTCAE will be measured, as well as, quality of life using the FACT-Lym, and will be compared between arms. The research was funded by: NIH/NCI/NCTN grants U10CA180888/U10CA180819 Keywords: aggressive B-cell non-Hodgkin lymphoma, molecular targeted therapies, ongoing trials No conflicts of interests pertinent to the abstract.