A phase 1b/2 study of CD30-specific chimeric antigen receptor T-cell (CAR-T) therapy in combination with bendamustine in patients with CD30+ Hodgkin and non-Hodgkin lymphoma.

TPS3095 Background: CAR-T therapy has emerged as one of the most promising therapeutic approaches for lymphoma. CD30 antigen is expressed on virtually all Hodgkin (HL) and various subtypes of non-Hodgkin lymphoma (NHL). HL and NHL are both sensitive to the cellular immune response and antibody-directed therapy, which makes CD30 an excellent target for CAR-Ts. In the “first-in-human” clinical trial of CD30.CAR-Ts, the dose of 2 × 10 8 CD30.CAR-Ts/m 2 was found to be safe; however, no conditioning therapy was given prior to CD30.CAR-T infusion and the expansion of CAR-Ts was thus limited. In the current study, we have further developed the CD30.CAR-T-based therapy by combining it with bendamustine. We hypothesized that bendamustine may improve therapeutic efficacy of CD30.CAR-Ts by causing sufficient depletion of endogenous immune cells to facilitate the expansion and persistence of CAR-Ts in vivo. Methods: In this phase 1b/2 clinical study, patients with CD30+ HL or NHL receive bendamustine followed by CD30.CAR-Ts (NCT02690545). The primary objective is to establish the safety of CD30.CAR-Ts in combination with bendamustine. Secondary objectives include estimation of 2-year overall and progression-free survival rates. Patients receive bendamustine (90 mg/m 2 on days 1 and 2) followed by CD30.CAR-Ts within 1 to 4 days of lymphodepletion. The maximal tolerated dose is determined based on 3 + 3 design for dose escalation starting at 1 × 10 8 CD30.CAR-Ts/m 2 . If the first 3 enrolled subjects do not experience a DLT within 6 weeks of the cell infusion, the number of cells for the infusion is increased to 2 x 10 8 /m 2 . Once the number of cells for infusion is established, up to 25 subjects will be enrolled in the Phase 2 portion of the study to further establish the safety and efficacy of this treatment regimen. Response will be assessed at 6 weeks after CD30.CAR-Ts infusion, and a second CD30.CAR-Ts infusion equal to or lower than the dose may be administered to patients with partial response or stable disease. Patient’s peripheral blood samples will be evaluated at various time points to monitor safety, function, and persistence of transduced T-cells. Clinical trial information: NCT02690545.