Marker Therapeutics has reported compelling scientific evidence from its Phase 1 APOLLO study demonstrating that lymphodepletion significantly improves the expansion and persistence of multi-antigen recognizing T cells (MAR-T) in patients with lymphoma. The company's lead product, MT-601, is showing promising results in patients who have relapsed after anti-CD19 chimeric antigen receptor (CAR)-T cell therapy or for whom such therapy is not an option.
According to data presented on May 20, 2025, T Cell Receptor (TCR) sequencing revealed that MT-601 MAR-T cell clones expanded and persisted at significantly higher levels in patients who received lymphodepletion compared to those who did not undergo the conditioning regimen. This enhanced in vivo expansion and persistence is believed to positively influence the clinical anti-tumor activity of MT-601.
"Our preliminary data clearly suggests that lymphodepletion increases the expansion and persistence of MT-601 in patients. This is the first time we have obtained this evidence in vivo and it provides a clear direction for our MAR-T cell studies going forward," said Juan Vera, M.D., President and CEO of Marker Therapeutics.
Early Clinical Efficacy and Safety Profile
The APOLLO study has already demonstrated encouraging clinical outcomes. With a data cutoff date of September 10, 2024, clinical data from nine patients across five U.S. clinical sites showed that MT-601 infusion was well tolerated in all study participants with no dose-limiting toxicities (DLTs), including immune-effector cell associated neurotoxicity syndrome (ICANS).
Notably, objective responses were achieved in seven out of nine patients (78%), with four patients demonstrating complete response (44.4%) as early as four weeks after MT-601 infusion. These responses were observed both with and without lymphodepletion, though the new data suggests lymphodepletion may further enhance outcomes.
Dr. Vera emphasized the significance of these findings: "Comparative data from previous studies suggest that incorporating lymphodepletion in our MAR-T cell trials may enhance clinical outcomes by boosting T cell expansion and anti-tumor activity. Consistent with this, our immunomonitoring data indicates that lymphodepletion leads to a more robust antigen-specific T cell response. Importantly, despite the incorporation of lymphodepletion, MT-601 continues to demonstrate an excellent safety profile."
Accelerating Enrollment and Trial Progress
The company also reported a significant increase in patient enrollment, driven by encouraging early clinical data and a shifting competitive landscape. In the first five months of 2025 alone, Marker enrolled and successfully manufactured product for more patients than in the entire year of 2024.
"We believe the incorporation of lymphodepletion was the right strategic decision as demonstrated by our immunomonitoring data. The incorporation of lymphodepletion has led to increased T cell expansion and persistence, which we believe has the potential to further enhance the clinical outcomes we are seeing. We are now enrolling at an increased pace and are well-positioned to generate meaningful data, which we expect to share by the end of this summer," Dr. Vera stated.
The MAR-T Cell Approach
MT-601 represents a novel approach to T cell therapy. Unlike conventional CAR-T therapies, MT-601 is a non-genetically modified cell therapy that specifically targets six different tumor antigens upregulated in lymphoma cells: Survivin, PRAME, WT-1, NY-ESO-1, SSX-2, and MAGEA-4.
The multi-antigen recognizing (MAR) T cell platform selectively expands tumor-specific T cells from a patient's or donor's blood capable of recognizing a broad range of tumor antigens. This approach allows for the recognition of hundreds of different epitopes within up to six tumor-specific antigens, potentially reducing the possibility of tumor escape.
Since MAR-T cells are not genetically engineered, Marker believes that its product candidates will be easier and less expensive to manufacture, with an improved safety profile compared to current engineered T cell approaches, while still providing patients with meaningful clinical benefits.
The APOLLO Trial Design
The APOLLO trial (NCT05798897) is a Phase 1, multicenter, open-label study evaluating the safety and efficacy of MT-601 in participants with relapsed or refractory lymphoma who have either failed anti-CD19 CAR-T cell therapy or are not candidates for such therapy.
The primary objective of this exploratory Phase 1 clinical trial is to evaluate the optimum dose, safety, and preliminary efficacy of MT-601 in participants with various lymphoma subtypes. Under the APOLLO trial, nine clinical sites across the United States are expected to enroll approximately 30 participants during the dose escalation phase.
The company anticipates presenting a comprehensive clinical data readout from the Phase 1 APOLLO study later this year, which will provide further insights into the potential of this innovative approach to T cell therapy for lymphoma patients with limited treatment options.
Scientific Context and Historical Perspective
The concept of lymphodepletion as a preconditioning regimen for cell therapies is not new. Similar correlations have been observed when using lymphodepletion with other T cell therapies, including CAR-T and tumor infiltrating lymphocyte (TIL) products. Previous studies have shown that while T cell therapies can be effective with and without lymphodepletion, the use of lymphodepletion was associated with improved clinical outcomes and enhanced expansion and persistence of T cells.
Marker's findings align with historical research dating back to Rosenberg's work published in the Journal of the National Cancer Institute in 1994, and more recent studies by Ramos et al. in the Journal of Clinical Oncology (2020) and Turtle et al. in Science Translational Medicine (2016).
The company's approach builds on this scientific foundation while introducing innovations that may address some of the limitations of current cell therapies, particularly for patients who have failed or are not candidates for standard CAR-T cell approaches.
