A single-arm, open-label, multi-center, phase 1b/2 Study to evaluate the safety, efficacy, and cellular pharmacokinetic profile of CTD402 in participants with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LBL) (TENACITY-01)

Abstract

Abstract Background and significance Relapsed/Refractory (R/R) T-ALL/LBL remains a significant therapeutic challenge due to lack of effective therapies. CTD402, is a novel universal (U) anti-CD7 CAR-T therapy, with T cell receptor, CD7, and human leukocyte antigen class II knockout to prevent graft vs host disease (GvHD), fratricide and immune rejection, respectively. Additionally, inhibitory (i1, i2, NKi) molecules are included to resist NK and T cell rejection. The CAR construct consists of a CD7-binding scFv, a 4-1BB costimulatory domain, a CD3ζ signaling domain, and a γc intracellular domain (common γ chain or CD132). Preliminary data from several investigator-initiated studies conducted across 9 centers in China (NCT05716113; NCT04620655; NCT05454241; NCT05907603; NCT05923541; NCT05902845; and NCT05895994) demonstrated an acceptable safety profile and initial evidence of anti-leukemic activity with high measurable residual disease (MRD) negative remission rates, and durable remissions, particularly in those participants who proceed to allogeneic stem cell transplantation (HSCT) (Lu, et al., EHA 2025; Hu et al). Herein we describe a global Phase 1b/2 study of CTD402 in R/R T-ALL/LBL; TENACITY-01 (NCT 07070219). Study Design and Methods TENACITY-01 is a single-arm, open-label, multi-center, Phase 1b/2 study to assess the safety and efficacy of CTD402 in adolescent and adult participants (age ≥12 years) with R/R T-ALL/LBL. Approximately 18 participants will be enrolled in the Phase 1b portion of the study to evaluate the safety and confirm the RP2D of CTD402. An additional 36 participants will be enrolled in the Phase 2 portion of the study to further validate the efficacy and safety of CTD402. All participants will receive a flat dose of 400 x 106CTD402 CAR-T cells on Day 0. Prior to the infusion of CTD402, participants will undergo standard lymphodepletion consisting of fludarabine (30mg/m2 x 3 days) and cyclophosphamide (500mg/m2 x 3 days) on days -5 to Day -2 with a 2-day rest period before infusion of CTD402 on Day 0. In the Phase 1b portion of the study, the dose of CTD402 may be escalated to 800 x 106 cells or de-escalated to a dose of 200 x 106 cells based on review of safety data by the Safety Review Committee. Key eligibility criteria include participants age 12 and older diagnosed with R/R T-ALL/LBL, defined as the presence of 5% bone marrow blasts or evidence of extramedullary disease, with one of the following: R/R disease after ≥ 2 lines of systemic therapy, first relapse ≤ 12 months of first remission, or any relapse after HSCT. Participants will be hospitalized for the first week after receiving CTD402. Disease assessments will involve the use of bone marrow aspirate, peripheral blood counts, physical examination and imaging assessments, as necessary. Participants may be administered an additional dose of CTD402 in the case of CD7-positive relapse occurring after a minimum of six months from the first CTD402 infusion. The primary objectives for the Phase 1b portion of the study include an assessment of safety as defined by incidence and severity of adverse events, including pre-defined dose limiting toxicities and GvHD. Phase 2 will assess the efficacy of CTD402 as defined by response rates and duration of response. Key secondary and exploratory objectives include MRD negativity and percentage of patients undergoing HSCT while in remission. Safety and response data will be evaluated by an independent review committee based on CTCAE, NCCN and Lugano 2014 response criteria, respectively. This trial will start enrolling patients initially in the US and Australia in 2nd half of 2025.