Bispecific Anti-CD20/19 CAR-T Zamtocabtagene Autoleucel Show Promising Results In R/R DLBCL

The DALY II USA study evaluated the safety and effectiveness of administering zamtocabtagene autoleucel (zamto-cel), a dual chimeric antigen receptor (CAR) T-cell therapy in patients (pts) with R/R diffuse large B-cell lymphoma (DLBCL).

Individuals eligible for the study were older than 18, with an Eastern Cooperative Oncology Group performance status of 0–1, and had R/R DLBCL following at least two previous rounds of systemic treatment. Utilizing bridging chemotherapy was prohibited. Apheresis material was dispatched to a central manufacturing facility in its fresh state, devoid of cryopreservation. The production of CAR-T cells was carried out over a fixed 12-day duration using the CliniMACS Prodigy® system by Miltenyi Biotec. A singular infusion of fresh zamto-cel, totaling 2.5×10⁶ cells/kg, was administered post lymphodepletion, initiated during the manufacturing phase to facilitate the delivery of fresh CAR-T cells. The study’s key objective was to assess the rate of response.

As of September 1, 2022, 28 pts were enrolled in the study and received treatment. Out of these, 22 pts were considered evaluable according to the protocol. A majority (69%) of the treated individuals displayed advanced disease, characterized by an International Prognostic Index (IPI) score of at least three and elevated baseline levels of lactate dehydrogenase (LDH). Additionally, 28% of the pts had previously undergone treatment with agents targeting CD19 and/or CD79. Six pts were not included in the primary efficacy analysis; one had received a frozen product, and five had received a fresh product that needed to meet the stipulated conformity criteria.

According to assessments conducted by the Independent Radiology Committee (IRC), out of the 22 evaluable pts, 18 (82%) exhibited a positive response to treatment, including complete responses (CR) in 46% and partial responses (PR) in 36%, surpassing the predefined futility threshold. The response rate within the evaluable group was comparable to that in all treated pts. Post-progression biopsies were obtainable from 5 pts, which revealed no isolated instances of CD19 loss. However, one patient lost dual targets, specifically CD19 and CD20, compared to their pre-treatment status. At the 6-month, the progression-free survival (PFS) rate was 64% among evaluable patients and 61% among the entire treated cohort. The administered treatment was well tolerated by the pts. Among all 28 treated pts, there were no Grade 3–4 cytokine release syndrome (CRS) instances. Only two cases of transient and reversible Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS)(9%) were observed. No instances of treatment-related mortality were recorded.

The interim analysis revealed that the anticipated efficacy threshold for zamto-cel was exceeded. Notably, the treatment showed a favorable safety profile, ORR, and PFS in an advanced diffuse DLBCL patient cohort previously treated with unavailable agents in analogous earlier studies. In addition, the study exhibited the practicability of a swift manufacturing procedure, ensuring a 100% fresh infusion of zamto-cel in eligible pts.

Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_96

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04792489

Ulrickson, M., Miklos, D. B., Maziarz, R. T., Jacobson, C., Isufi, I., Ghosh, M., Perales, M., Lunning, M., Hardy, N. M., Wijatyk, A., Ancukiewicz, M., Nallewar, M., Coleman, K. C., Prudner, B. C., Eromosele, E., Kaleta, R., Shah, N. N. BISPECIFIC ANTI-CD20/19 CAR-T—ZAMTOCABTAGENE AUTOLEUCEL FOR RELAPSED/REFRACTORY DLBCL—INTERIM ANALYSIS RESULTS OF DALY-II-USA STUDY https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_96