Swog 2114: a randomized phase ii trial of consolidation therapy following cd19 car t‐cell treatment for relapsed/refractory large b‐cell or grade iiib follicular lymphoma

Introduction: CD19 CAR T-cell therapy (CD19 CTCT) is now the standard of care for many patients (pts) with relapsed/refractory large cell lymphoma (LCL), but nearly two-thirds of patients will still progress. Relapsed disease post CD19 CTCT is poorly responsive to subsequent therapies, and patient survival is dismal. (Spiegel JY, et al. Blood, 2021) Thus, we designed a clinical trial to assess the safety and efficacy of new consolidation regimens for LCL pts at high risk for relapse, which we define as stable disease (SD) or partial remission (PR) at one month PET-CT after CD19 CTCT. Polatuzumab vedotin (P) and mosunetuzumab (M) have proven efficacy in LCL, anticipated safety post CD19 CTCT, and lack of detriment to circulating CAR T-cells. The objective of this trial is to prevent relapse in this high-risk population with safe and effective consolidation therapies in order to improve outcomes. Methods: This is an NCI sponsored phase II study with two registration steps. (Figure 1) Step 1 registration: All pts with relapsed/refractory LCL or FL grade 3b who are candidates for FDA approved ≥2nd line CD19 CTCT including tisagenlecleucel, axicabtagene ciloleucel, lisocabtagene maraleucel will be eligible. Pts must enroll prior to the start of lymphodepleting chemotherapy preceding the CD19 CTCT infusion. Bridging therapy is allowed after apheresis as long as it does not include P or M. Previous P is allowed outside of bridging unless pt has progressed within 6 months of last dose. Step 2 randomization: All pts enrolled in step 1 will undergo one month PET-CT between days +25-40 post CD19 CTCT which will be centrally reviewed by the Imaging and Radiation Oncology Core (IROC). Pts with SD/PR by central review will be eligible for randomization to one of three consolidation arms (M, P, M+P) or observation (O) in a 1:1:1:1 fashion. Those in CR will continue to be followed on the biomarker assay/PRO portion of the protocol without any therapy initiated while those with progressive disease will be treated per MD discretion. All pts will be followed for survival outcomes. Primary endpoint: Compare the 1-year PFS of each consolidation arm vs observation (M vs O, P vs O, M+P vs O). An estimated 120 pts (30 in each arm) are needed to detect a hazard ratio of 2 from estimated 25% 1 year PFS of the observation arm to 50% 1 year PFS of the each consolidation arm. It is estimated that 396 pts will need to be enrolled in step 1 registration to randomize 120 pts with SD/PR at one month PET-CT in the step 2 randomization. Cross-over design: Pts with SD/PR randomized to the observation arm are eligible to receive M+P if they have definitive progression within 1 year of CD19 CTCT infusion. Correlatives/PRO: Correlative and PRO assessments will occur at scheduled imaging timepoints for all pts registered to step 1. Minimal residual disease will be a focus and be followed in all pts regardless of one month PET-CT response post CD19 CTCT. Keywords: cellular therapies, ongoing trials Conflicts of interests pertinent to the abstract. B. Hess Consultant or advisory role ADC Therapeutics, BMS J. Svoboda Consultant or advisory role SEAGEN, Pharmacyclics, Incyte, Genmab, BMS, Atara, Astra Zeneca, Adaptive, ADC Therapeutics Research funding: TG, SEAGEN, Pharmacyclics, Merck, Incyte, BMS, Astra Zeneca, Adaptive