Novel Anti-CD5 Therapy Earns FDA RMAT Designation in T-Cell Lymphoma

The FDA based its decision on preliminary findings from a phase 2 trial (NCT06534060) assessing MB-105 in relapsed/refractory CD5-positive T-cell lymphoma. In the safety run-in cohort of the trial, the investigational CAR T-cell therapy produced evidence of clinical activity and demonstrated a manageable safety profile.

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to the investigational anti-CD5 CAR T-cell therapy MB-105 as a treatment for those with relapsed/refractory CD5-positive T-cell lymphoma, according to a press release from the developer, March Biosciences.1

Developers engineered MB-105 as a possible first-in-class agent for CD5-positive blood cancers, which includes T-cell lymphoma, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and mantle cell lymphoma. The therapy may selectively target malignant cells with streamlined manufacturing and no additional genetic manipulation based on a proprietary CAR design. According to the press release, the FDA previously granted orphan drug designation to MB-105 in the same T-cell lymphoma population.

The FDA based its decision on preliminary findings from a phase 2 trial (NCT06534060) assessing MB-105 in relapsed/refractory CD5-positive T-cell lymphoma. In the safety run-in cohort of the trial, the investigational CAR T-cell therapy produced evidence of clinical activity and demonstrated a manageable safety profile.

Investigators plan to present initial data from this cohort at the 2025 American Society of Hematology Annual Meeting and Exposition (ASH).2 Further updates from the trial are anticipated in 2026. Additionally, developers plan to discuss the next potential steps for an expedited development and review pathway for MB-105 with the FDA.

“The FDA’s RMAT designation further validates MB-105’s potential to address a critical unmet medical need for patients with relapsed/refractory T-cell lymphoma, who [have] a median survival of only 6 months with current therapies,” Sarah Hein, co-founder and chief executive officer at March Biosciences, stated in the press release.1 “We are encouraged by the responses observed to date and look forward to working closely with the FDA to advance MB-105 as efficiently as possible.”

Investigators of the multicenter phase 2 trial are enrolling patients across 12 sites in the US. Stage 1 of the trial was designed to include 15 patients, with the first 6 enrolled patients receiving 1 dose of MB-105 at the recommended phase 2 dose (RP2D) and an independent data monitoring committee performing a subsequent safety analysis.3 Additionally, stage 2 of the trial was planned to include approximately 31 patients, yielding a total population of 46.

The trial’s primary end points included incidence, severity, and causal relationships of adverse effects (AEs) per CTCAE v5.0 criteria and objective response rate per independent central review using 2014 Lugano criteria and 2022 Global criteria. Secondary end points included duration of response, progression-free survival, incidence of select AEs during the safety monitoring period for acute toxicities, and overall survival.

Patients 18 years and older with relapsed/refractory T-cell lymphoma per WHO 2022 guidelines, available tumor tissue or willingness to undergo a biopsy procedure, CD5-positive status confirmed via local laboratory testing, and a Karnofsky performance status of 70% or higher were eligible for enrollment on the trial. Other eligibility criteria included having measurable or detectable disease, adequate bone marrow function, and adequate organ function. Patients were permitted to have prior autologous or allogenic hematopoietic stem cell transplant more than 60 days before study entry.

Those with Sezary syndrome, contraindications to leukapheresis, or any prior treatment with CD5-directed agents were ineligible for enrollment on the trial. Patients were also ineligible for study entry if they had any evidence of HIV infection, chronic hepatitis B virus, or hepatitis C infection with detectable viral load; active central nervous system lymphoma; prior donor lymphocyte infusions within 28 days of beginning treatment with MB-105; and a history of autoimmune disorders, including rheumatic diseases and thyroid disorders.

References

1. March Biosciences receives FDA regenerative Medicine Advanced Therapy (RMAT) Designation for MB-105 in relapsed/refractory CD5-positive T-cell lymphoma. News release. March Biosciences, Inc. November 11, 2025. Accessed November 12, 2025. https://tinyurl.com/4r9ysbca
2. March Biosciences announces oral presentation of MB-105 interim phase 2 clinical data at American Society of Hematology Annual Meeting. News release. March Biosciences, Inc. November 3, 2025. Accessed November 12, 2025. https://tinyurl.com/yc8jpra7
3. MB-105 in patients with CD5 positive T-cell lymphoma. ClinicalTrials.gov. Updated October 3, 2025. Accessed November 12, 2025. https://tinyurl.com/59998dzp