Allotera Therapeutics Opens MRD-Positive Cohort in Pivotal T-RRex Study of Sofi-cel for T-ALL and T-LBL
Allotera Therapeutics, Inc., a clinical-stage biotechnology company developing allogeneic, off-the-shelf cell therapies for hematological malignancies, announced the opening of a new minimal residual disease (MRD)-positive cohort in its global pivotal T-RRex clinical study evaluating Soficabtagene Geleucel (Sofi-cel).
The expansion of the study will allow Allotera to evaluate Sofi-cel in patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) who have achieved remission following standard therapy but continue to have detectable minimal residual disease. The company is investigating whether treating patients at this stage of the disease, before overt relapse occurs, could help eliminate residual malignant cells and potentially improve longer-term outcomes.
The newly opened cohort expands the clinical development strategy for Sofi-cel beyond patients with relapsed or refractory disease. The T-RRex study already includes a pivotal cohort evaluating the investigational therapy in patients with relapsed or refractory T-ALL and T-LBL, while the MRD-positive cohort will assess the therapy earlier in the treatment continuum.
Targeting Residual Disease Before Relapse
Minimal residual disease refers to a small number of cancer cells that can remain in the body after treatment even when a patient appears to be in clinical remission. In acute leukemia, the presence of detectable MRD following treatment can indicate that malignant cells remain and may be associated with an increased risk of disease recurrence.
For patients with T-ALL or T-LBL, identifying and treating residual disease is therefore an important area of clinical research. While patients may achieve remission following initial therapy, persistent MRD can represent a significant challenge because conventional assessments may show remission despite the continued presence of small numbers of malignant cells.
Allotera’s new MRD-positive cohort is designed to investigate whether Sofi-cel can address this residual disease in patients who have not yet experienced a clinical relapse.
“Opening the MRD-positive cohort allows us to reach patients earlier in their disease course, before relapse, when we believe Sofi-cel may have the potential to provide meaningful clinical benefit,” said Kumar Srinivasan, Ph.D., M.B.A., President and Chief Executive Officer of Allotera.
According to Srinivasan, expanding T-RRex into the MRD-positive population reflects the company’s broader effort to investigate Sofi-cel across different points in the treatment journey for patients with T-ALL and T-LBL.
The company is evaluating the investigational cell therapy in both patients with relapsed or refractory disease and those who remain in remission but have detectable MRD following standard treatment.
Sofi-cel and Allogeneic Cell Therapy
Sofi-cel is being developed by Allotera as an allogeneic, off-the-shelf cell therapy. Unlike autologous cell therapies, which are manufactured using a patient’s own cells, allogeneic approaches use cells obtained from a donor source.
The off-the-shelf approach is intended to support the availability of cell therapy without requiring individualized manufacturing for every patient. In the context of hematological malignancies, such an approach could potentially provide a more readily available treatment option, although the clinical benefits and limitations of Sofi-cel remain under investigation in the ongoing study.
Allotera is developing Sofi-cel for T-ALL and T-LBL, two related hematological malignancies involving immature T cells. T-ALL is a form of acute leukemia characterized by the abnormal proliferation of immature T lymphoblasts, while T-LBL is a related disease that primarily involves lymphoblasts in tissues rather than the bone marrow.
Both diseases can require intensive treatment, and patients whose disease returns or does not adequately respond to initial therapy may have limited treatment options. The T-RRex study is intended to evaluate whether Sofi-cel can provide clinical activity in these patient populations and whether the therapy may also have a role in treating persistent MRD.
T-RRex Study Design
The T-RRex study is a global, single-arm, open-label Phase 2 clinical trial with a pivotal cohort evaluating Sofi-cel in patients with relapsed or refractory T-ALL and T-LBL.
The study is also evaluating Sofi-cel in patients who have achieved remission following standard therapy but remain MRD-positive.
The trial is being conducted across 18 clinical sites in the United States and Australia, providing a multinational clinical development framework for the investigational therapy.
The addition of the MRD-positive cohort represents an important expansion of the study population because it allows investigators to evaluate Sofi-cel at a point when patients remain in remission but have evidence of residual disease.
The approach differs from treating patients only after their cancer has returned clinically. Instead, investigators will assess whether intervening when MRD is detected can eliminate residual malignant cells before they develop into overt relapse.
Potential Role of MRD-Negative Remission
A central objective of the new cohort is to determine whether treatment with Sofi-cel can lead to MRD-negative remission.
MRD-negative status indicates that residual disease is no longer detectable using the assessment method employed. Achieving MRD negativity can be an important treatment goal in acute leukemia because persistent detectable disease can be associated with an increased risk of relapse.
“MRD positivity after standard therapy is one of the strongest predictors of relapse, yet few therapies are directed specifically at eliminating residual disease,” said Cherry Thomas, M.D., Chief Medical Officer of Allotera.
Thomas said the company intends to use the MRD-positive cohort to investigate whether Sofi-cel can achieve MRD-negative remission and whether this could ultimately translate into improved long-term clinical outcomes.
The study’s findings will be important in determining whether the investigational therapy has potential in patients who have residual disease after standard treatment but have not yet experienced a clinical relapse.
Because the MRD-positive cohort has only recently opened, clinical outcomes remain to be determined. The ongoing trial will generate the evidence needed to evaluate the safety, tolerability and potential efficacy of Sofi-cel in this earlier treatment setting.
Expanding Sofi-cel Across the Treatment Continuum
Allotera’s strategy for Sofi-cel now encompasses different stages of T-ALL and T-LBL treatment.
The pivotal portion of the T-RRex study is evaluating patients with relapsed or refractory disease, a population in which cancer has either returned following treatment or has failed to respond adequately to prior therapy.
The newly opened cohort moves the investigation into an earlier setting. Participants in this group will have achieved remission following standard therapy but continue to test positive for MRD.
This approach gives researchers an opportunity to evaluate Sofi-cel in patients before the disease has progressed to overt relapse.
For Allotera, studying the therapy across these distinct patient populations could provide a broader understanding of where an allogeneic cell therapy might fit within the treatment pathway for T-ALL and T-LBL.
However, the potential clinical role of Sofi-cel will depend on the results of the ongoing clinical investigation. The opening of the MRD-positive cohort does not establish efficacy, and additional data will be required to determine whether treatment can produce durable MRD-negative responses or improve long-term outcomes.
Addressing an Unmet Need in T-Cell Malignancies
T-ALL and T-LBL are aggressive hematological malignancies that can require intensive treatment. Patients who experience persistent disease after standard therapy or whose disease becomes relapsed or refractory can face significant clinical challenges.
The presence of MRD provides physicians and researchers with an additional measure of disease status that can identify residual malignant cells even when a patient has achieved an apparent remission.
The new T-RRex cohort is consequently focused on an important clinical question: whether treating detectable residual disease before overt relapse can change the course of the disease.
Allotera believes Sofi-cel may have potential in this setting because of its development as an off-the-shelf allogeneic cell therapy. The company is now testing that hypothesis prospectively through the expanded Phase 2 study.
The multinational nature of the T-RRex trial, with sites across the United States and Australia, will allow the company and investigators to collect clinical data across multiple centers as the study advances.
Next Steps for the Clinical Program
With the MRD-positive cohort now open, recruitment and clinical evaluation will continue alongside the existing study activities in relapsed or refractory T-ALL and T-LBL.
Investigators will assess the performance of Sofi-cel in patients with persistent MRD after standard therapy and determine whether the investigational treatment can eliminate detectable residual disease.
Future findings from the study may help clarify the safety profile of Sofi-cel in the MRD-positive setting, its ability to achieve MRD-negative remission and whether those responses can potentially translate into longer-term disease control.
For Allotera, the expansion of T-RRex represents a step toward evaluating Sofi-cel across a wider portion of the treatment continuum. The company is pursuing an approach that combines allogeneic, off-the-shelf cell therapy with earlier intervention against residual disease.
As the study progresses, clinical data from both the relapsed/refractory and MRD-positive populations will be important in determining the potential role of Sofi-cel in T-ALL and T-LBL. The ongoing investigation will ultimately provide the evidence needed to assess whether targeting residual disease before relapse can offer a meaningful therapeutic benefit for patients with these hematological malignancies.
About Soficabtagene Geleucel (Sofi-cel)
Sofi-cel is an allogeneic, off-the-shelf, CD7-targeted CAR-T cell therapy being developed for T-cell cancers. Allotera uses CRISPR/Cas9 gene editing to delete CD7 and the T-cell receptor alpha constant (TRAC) genes, an approach intended to prevent CAR-T cell fratricide and mitigate the risk of graft-versus-host disease.
Sofi-cel is manufactured in the United States using healthy donor-derived T cells, which is intended to avoid malignant cell contamination that can occur in the autologous CAR-T setting. Sofi-cel is currently being evaluated in a global pivotal clinical trial for relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma and patients who are in remission but remain MRD-positive following standard therapy. More information on the pivotal trial is available at ClinicalTrials.gov, identifier NCT06514794.
Sofi-cel has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration for the treatment of relapsed or refractory T-ALL/T-LBL, as well as Priority Medicines, or PRIME, designation in the European Union. RMAT and PRIME designations provide increased agency support to expedite the development and review of promising therapies for patients with medical need. Sofi-cel was also selected to participate in the FDA’s Chemistry, Manufacturing, and Controls Development and Readiness Pilot Program.
About Allotera Therapeutics
Allotera Therapeutics, Inc. is a clinical-stage biotechnology company developing allogeneic, off-the-shelf CAR-T cell therapies for cancer. The company is advancing Soficabtagene Geleucel, or Sofi-cel, its lead CD7-targeted CAR-T cell therapy, through a global pivotal study for relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.
Allotera’s gene-editing and manufacturing approach is intended to address key biological and practical barriers that have limited CAR-T therapy development in T-cell cancers. Headquartered in St. Louis, Missouri, Allotera is working to expand what off-the-shelf cell therapy can mean for patients with aggressive hematological malignancies.