FDA Grants RMAT Designation to Lasme-Cel for Relapsed/Refractory B-ALL

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to lasmecabtagene timgedleucel (lasme-cel; UCART22), a CD22-targeting allogeneic chimeric antigen receptor (CAR) T-cell therapy, for the treatment of adults and adolescents with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). The designation makes lasme-cel the first allogeneic CAR T therapy to receive RMAT designation while simultaneously enrolled in a pivotal trial for this indication.¹

The designation was supported by phase 1 data from the BALLI-01 trial (NCT04150497), which demonstrated clinically meaningful response rates and a manageable safety profile in a heavily pretreated patient population. The pivotal phase 2 portion of BALLI-01 is currently open for enrollment, with a first interim analysis expected in the fourth quarter of 2026.

Clinical Context and Unmet Need

R/R B-ALL carries a poor prognosis in adults, with outcomes deteriorating substantially with each successive line of therapy. A large retrospective study of more than 17,000 adult patients with R/R ALL reported an overall complete remission (CR) rate of approximately 40% following first-line salvage therapy, declining to 21% after second-line salvage and 11% after third-line or later salvage. Median overall survival (OS) was 5.8 months, 3.9 months, and 2.9 months in those respective settings.² Despite advances with agents such as blinatumomab (Blincyto) and inotuzumab ozogamicin (Besponsa), durable remission remains difficult to achieve, and most patients are managed with the goal of bridging to allogeneic hematopoietic stem cell transplantation (alloHSCT).

The existing autologous CAR T landscape in B-ALL centers primarily on CD19-directed therapies. However, CD19 antigen loss following prior CAR T or blinatumomab exposure represents a recognized mechanism of relapse, leaving a subset of patients without viable targeted options.³ Lasme-cel addresses this through CD22 targeting, an approach that is not affected by CD19 loss and may therefore benefit patients who have exhausted CD19-directed strategies.

RMAT Designation: Regulatory Significance

The RMAT designation was established under Section 3033 of the 21st Century Cures Act, which amended Section 506(g) of the Federal Food, Drug, and Cosmetic Act. To qualify, an investigational product must meet the definition of a regenerative medicine therapy, be intended to treat a serious or life-threatening condition, and demonstrate preliminary clinical evidence of its potential to address an unmet medical need.⁴

Phase 1 BALLI-01 Trial

The BALLI-01 trial is a phase 1/2, open-label, dose-escalation and expansion study of lasme-cel in patients with R/R B-ALL. The phase 1 component enrolled 40 patients aged 15 to 70 years with greater than 70% CD22 expression on leukemic blasts, who were ineligible for transplant at study entry and had received at least three prior lines of therapy.¹

The phase 1 population was heavily pretreated: participants had received a median of 4 prior lines of therapy, 80% had prior blinatumomab exposure, and approximately half had received prior inotuzumab ozogamicin and prior autologous CD19-directed CAR T therapy. Lasme-cel was administered following lymphodepletion conditioning with fludarabine and cyclophosphamide (FC) or, in later cohorts, FC combined with alemtuzumab (Campath; FCA). The addition of alemtuzumab was implemented to sustain host T-cell and natural killer cell depletion and support lasme-cel expansion and persistence.

Phase 1 data are reported separately for 2 manufacturing processes: an external contract development and manufacturing organization process (Process 1, or P1; n = 18) and an in-house Cellectis manufacturing process (Process 2, or P2; n = 22). Overall CR/CR with incomplete hematologic recovery (CRi) rates were 18% for P1 and 36% for P2, with P2 demonstrating superior activity.

At dose level 3 with P2 (DL3/P2), designated the recommended phase 2 dose (RP2D), 12 patients were treated. The CR/CRi rate was 42%, with 80% of responders achieving minimal residual disease (MRD)-negative status.

In the subset of 9 patients meeting the criteria of the target pivotal phase 2 population (P2, DL3, age ≤50 years):

• Overall response rate (ORR): 100%
• CR/CRi rate: 56%
• MRD-negativity among CR/CRi responders: approximately 80%
• Transplant eligibility achieved: 100%, with 78% proceeding to alloHSCT

Among 11 patients who had received all 3 available targeted therapies, 8 responded and 7 achieved MRD-negative status. In patients who achieved MRD-negative CR/CRi, median OS was 14.8 months.

Phase 1 Safety Data

The phase 1 safety profile was consistent with expectations for CAR T–based therapies. In the overall cohort of 40 patients, cytokine release syndrome (CRS) was observed in 2.5% of patients and immune effector cell–associated neurotoxicity syndrome (ICANS) in 5%, with 1 case of grade 2 immune effector cell–associated hemophagocytic lymphohistiocytosis syndrome (IEC-HS) that resolved. Dose-limiting toxicities were uncommon, with a single dose-limiting toxicity reported at DL3. Eight lasme-cel–related serious adverse events were reported across the phase 1 cohort.

The low rates of high-grade CRS and ICANS observed with lasme-cel are notable in the context of allogeneic CAR T therapy, where graft-vs-host disease (GVHD) and engraftment-related toxicity represent additional safety considerations relative to autologous approaches.

REFERENCES

1. Cellectis Receives FDA RMAT Designation for lasme-cel, the First Allogeneic CAR-T Therapy in a Pivotal Trial for Patients with r/r B-ALL. News release. Cellectis. June 9, 2026. Accessed June 11, 2026. https://tinyurl.com/y9h25y65

2. Bruzzese A, Martino EA, Labanca C, et al. Therapeutic Strategies for Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients: Optimizing the Use of Monoclonal Antibodies. Eur J Haematol. 2025 Jun;114(6):938-952. doi: 10.1111/ejh.14405. Epub 2025 Mar 6. PMID: 40045912; PMCID: PMC12053959.

3. Minnema MC, Yin X, Davi R, et al. Outcomes of patients aged ≥26 years with relapsed or refractory B-cell acute lymphoblastic leukemia in ZUMA-3 and historical trials. Leuk Lymphoma. 2024 Oct;65(10):1438-1447. doi: 10.1080/10428194.2024.2353877. Epub 2024 May 24. PMID: 38785408.

4. US Food and Drug Administration. Regenerative medicine advanced therapy designation. Accessed June 11, 2026. https://tinyurl.com/jex9fbaf