Cellectis has reported encouraging Phase 1 results for its allogeneic CAR-T therapy lasme-cel (UCART22) in heavily pretreated patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), demonstrating significant clinical activity that enabled most patients to proceed to potentially curative stem cell transplantation. The company has now initiated the pivotal Phase 2 portion of the BALLI-01 study following successful regulatory meetings.
Strong Efficacy in Heavily Pretreated Population
The Phase 1 BALLI-01 study enrolled 40 transplant-ineligible patients aged 15-70 years with r/r B-ALL in the third line or beyond, who had exhausted most treatment options. Patients were heavily pretreated with a median of 4 prior lines of therapy, with 80% having received prior blinatumomab and approximately half having received prior inotuzumab and CD19 autologous CAR-T therapy.
In the target Phase 2 population of 9 patients (Process 2, Dose Level 3, age ≤50), lasme-cel achieved remarkable results with a 100% overall response rate (ORR) and 78% achieving minimal residual disease-negative (MRD-negative) status. The complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 56%, with 80% of responders achieving MRD-negative status.
"The depth of response we observed, enabling a high percentage of patients in the study to proceed to transplant, with the potential for durable remission, is clinically meaningful," said Adrian Kilcoyne, MD, MPH, MBA, Chief Medical Officer of Cellectis.
Manufacturing Process Optimization Shows Impact
The study revealed significant differences between manufacturing processes, with Cellectis-manufactured product (Process 2) demonstrating superior efficacy compared to externally manufactured product (Process 1). In the overall Process 2 cohort of 22 patients, the ORR was 68%, compared to lower response rates with Process 1.
At the recommended Phase 2 dose (Dose Level 3, Process 2), 12 patients were treated, achieving a CR/CRi rate of 42% with 80% of responders reaching MRD-negative status. Notably, the therapy maintained efficacy even in patients who had relapsed after prior CD22-targeted therapy with inotuzumab, with 31% of these heavily pretreated patients achieving CR/CRi with MRD-negative status.
Bridge to Transplant Strategy Proves Effective
A key finding was lasme-cel's ability to serve as an effective bridge to transplant. In the target Phase 2 population, 100% of patients became transplant eligible, with 78% proceeding to hematopoietic stem cell transplantation (HSCT). Among patients who achieved MRD-negative CR/CRi, the median overall survival was 14.8 months, with survival curves suggesting clear benefit for patients who proceeded to HSCT after lasme-cel therapy.
"Our strategy is to achieve minimal residual disease-negative complete remission to create a window for hematopoietic stem cell transplantation and meaningfully improve overall survival," explained André Choulika, Ph.D., Chief Executive Officer of Cellectis.
Manageable Safety Profile
The Phase 1 safety data confirmed that lasme-cel was generally well-tolerated, with manageable adverse events typical of CAR-T therapies. Dose-limiting toxicities were uncommon, with only one case reported at Dose Level 3. Cytokine release syndrome (CRS) occurred in 2.5% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 5% of patients. Eight lasme-cel-related serious adverse events were reported across the 40-patient cohort.
Regulatory Path and Commercial Potential
Following successful End-of-Phase 1 meetings with the FDA and European Medicines Agency (EMA), Cellectis has established a registration path for lasme-cel as a bridge to transplant in r/r B-ALL. The first patient in the pivotal Phase 2 is expected to be enrolled in Q4 2025, with a Biologics License Application anticipated in 2028.
The company estimates lasme-cel could reach approximately 1,900 addressable third-line or beyond B-ALL patients annually by 2035 across the U.S., EU4 (Germany, France, Spain, Italy), and UK. With illustrative pricing of approximately $515,000 in the U.S. and $365,000 in EU4/UK, lasme-cel could achieve up to $700 million in potential peak gross sales by 2035, with potential expansion to $1.3 billion if approved for earlier treatment lines.
Additional Pipeline Progress
Cellectis also reported preliminary data on eti-cel (UCART20x22), its allogeneic CAR-T candidate for relapsed/refractory non-Hodgkin lymphoma, showing an 86% ORR and 57% complete response rate at the current dose level in 7 patients. The company continues its strategic collaboration with AstraZeneca to develop up to 10 novel cell and gene therapy products across oncology, immunology, and rare genetic disorders.
