CTD402, allogeneic anti-CD7 CAR t-cell, in relapsed or refractory (R/R) t-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) - report of clinical outcomes at the recommended phase 2 dose (RP2D) Free

Background R/R T-ALL/LBL poses significant therapeutic challenge due to paucity, and limited efficacy, of treatments. CTD402, is a CD7 targeted “off-the-shelf” universal CAR-T product with T cell receptor and human leukocyte antigen class II knockout, and improved resistance to host immune rejection achieved by arming the cells with proprietary ANSWER^TM inhibitory ligands. CTD402 is currently being developed for the treatment of T-cell hematologic malignancies and other severe blood disorders with ~100 patients (pts) treated in several Phase I/II trials, conducted across 9 centers in China ( NCT05716113; NCT04620655; NCT05454241; NCT05907603; NCT05923541; NCT05902845; and NCT05895994). Herein we present the data of a cohort of these pts treated at the RP2D.

Methods The RP2D of CTD402 is 400 million (M) cells administered on day (D) 0 following standard lymphodepleting chemotherapy (sLD)consisting of fludarabine (30 mg/m²/day) and cyclophosphamide (500 mg/m²/day) from days -5 to -3; this is the starting dosing regimen on the ongoing global clinical study (NCT# 07070219).

Results Up to a data cutoff June 30^th, 2025, 41 R/R T-ALL/LBL (27 ALL, 13 LBL, 1 MPAL) pts, median age 27 years (range 10-56), were treated at the RP2D. Pts had received a median of 2 prior lines of therapy (range 1-6), 37% were primary induction failure, and 24% had relapsed post allogenic hematopoietic stem cell transplant (allo-HSCT); 56% had high-risk molecular profile including ETP phenotype, RAS/PTEN alterations, NOTCH1/FBXW7^WT, or complex karyotype. Baseline disease burden was median bone marrow (BM) blasts of 42% (range 6.5-98.5%), 54% pts had extramedullary (EMD), including 1 pt with CNS leukemia.

Post-infusion,78.0% (n=32) pts experienced cytokine release syndrome, mostly mild Grade [G] 1-2 in 27 (65.9%) and G3 in 5 (12.2%) pts. No pt experienced immune effector cell-associate neurotoxicity or GvHD; Severe treatment-related infections (≥ G3) loccurred in only 5 (12.2%) pts and largely resolved with antibiotic therapy. Cytopenia was the most common AE noted post treatment with neutrophil (ANC) and platelet count recovery to grade ≤2 by D21 and D7 post-infusion, respectively. Lymphopenia nadired on D0 following lymphodepletion, with absolute lymphocyte count (ALC) recovery to G≤2 in 45%, 48.6%, and 70% of responders at D42, D56, and M3, respectively, post-infusion.

PK analysis revealed Cmax of median 1.2 ×10⁶copies/μg DNA (range 0.05-8.2x10⁶) occurred at a median Tmax of 10 days, with median AUC_0-28of 5,880,936. CTD402 persistence ≥ 28 days was noted in 59% of pts and 71% of responders, with persistence extending ≥ 90 days in some pts.

CD7^pos T-cells were depleted for the duration of CAR-T persistence with a compensatory increase in CD7^neg T-cells by day D21even in the presence of CTD402. Notably, CD7^neg T-cells from post-CD7 CAR patients could respond to viral peptides by producing interferon-γ, like T cells from healthy donors, suggesting that these CD7^neg T-cells retained immune-protective functions.

Among the 39 evaluable pts, complete remission rate (CRR) was 64.1% (n=25, 19 CR, 6 CRi ) with an impressive 91.7% (22/24 in pts evaluated) MRD^negrate. With a median follow up time of 21.2 months (range 0.8-25.5), the median DOR was 9.7 months (95% CI: 5.0 - not reached [NR]). Among the most challenging groups to treat, high-risk (n=23) or EMD pts (n=22), the CRR was 60.9% (8 CR,6 CRi; MRD^neg85.7%) and 59% (10 CR, 3 CRi; MRD^neg92.3%), respectively. Twelve (30.8%) pts received consolidative allo-HSCT post-CTD402 in remission (CR/CRi). Median overall survival was significantly higher in pts that received a consolidative transplant in remission vs the pts that did not, NR vs 7.3 (95% CI: 2.7-NR), p=0.0016, respectively.

Conclusion CTD402 demonstrated an acceptable safety profile and evidence of anti-leukemic activity with high MRD negative remission rates, and lasting benefits—especially when paired with allo-HSCT, that far exceeds the current standard of care. High response rate in particularly challenging to treat populations, high-risk and EMD positive disease, is particularly promising. This program advances an “off-the-shelf” ready at point of care CAR-T cell therapy in heavily pre-treated patients with R/R T-ALL/LBL. A global Phase 1b/2 study is ongoing and currently enrolling patients (NCT# 07070219).