Mustang reported new data and responses from a multicenter phase 1 trial evaluating its CAR T-cell therapy in patients with NHL, FL, and WM.
MB-106, Mustang Bio’s CD20-targeted chimeric antigen receptor (CAR) T-cell therapy, has demonstrated efficacy and safety in patients with indolent lymphoma treated in a phase 1/2 clinical trial (NCT05360238).
“We are encouraged that the first data from the multicenter trial of our lead candidate, MB-106, show clinical responses and that the trial is on track to achieve results consistent with those from the ongoing trial taking place at Fred Hutch,” Manuel Litchman, MD, president and chief executive officer, Mustang, said in a statement. “Overall, MB-106 continues to exhibit high efficacy and a favorable safety profile compared to currently approved autologous CAR-Ts. We expect to provide an additional update on dose escalation and report response data at a major medical meeting later this year.”
Investigators found that all 4 patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL) responded to the starting dose of 3.3 x 106 CAR T-cells/kg, a similar dose to that employed in the trial ongoing at Fred Hutchinson Cancer Center. Two patients with follicular lymphoma (FL) had complete responses (CRs), one of whom had previous CD19-CAR T-cell treatment. One patient with Waldenstrom macroglobulinemia (WM) had a complete metabolic response, morphologic clearance of lymphoma in bone marrow, and resolution of the IgM monoclonal protein after MB-106 treatment in the tenth-line setting. Another patient, with hairy cell leukemia, has continued to have stable disease with improvements in bone marrow and transfusion independence at over 6 months post-treatment.
The CAR T-cells were found to be persistent at over 6 months and patients have experienced only grade 1 cytokine release syndrome (CRS) so far. Based on these updated data, the Safety Review Committee has unanimously approved dose escalation to 1.0 x 107 CAR-T cells/kg.
“MB-106 continues to show potential as an immunotherapy option for patients with a wide range of hematologic malignancies, including patients previously treated with CD19-directed CAR-T cell therapy,” Mazyar Shadman, MD, MPH, study chair and Innovators Network Endowed Chair, Fred Hutch, and Associate Professor and physician, University of Washington, added. “We are excited that the first data from the expanded evaluation of MB-106 are similar in safety as what we’ve seen to date in the ongoing Phase 1/2 clinical trial at Fred Hutch. Additionally, the data from the ongoing clinical trial at Fred Hutch continue to demonstrate a high rate of complete and durable responses.”
Shadman also presented data from the Fred Hutch trial that demonstrated an overall response rate of 95%, a CR rate of 80%, and a partial response rate of 15% in a cohort of 20 patients with FL. One of 6 patients that experienced CRS had a grade 2 case. Ongoing CRs include 10 over 10 months, 4 over 2 years, and 1 over 3 years. The WM cohort of 6 patients that had received prior Bruton tyrosine kinase inhibitor had a CR rate of 33%, with 1 CR ongoing at over 22 months, but all patients not needing to start new therapy. This cohort had no CRS or immune effector cell-associated neurotoxicity syndrome casesover Grade 2.
The multicenter study expected to treat up to 18 patients per 3 arms in escalating dose levels in phase 1. Specific arms may be chosen to continue dosing at the recommended phase 2 dose in phase 2, with priority to WM and diffuse large B-cell lymphoma. Each arm will initially include up to 20 patients which may be expanded to an additional 51 patients. Mustang plans to treat the first patient in the phase 2 WM trial in mid-2024, potentially enabling top-line data as early as mid-2026. The company is planning an end-of-Phase 1 meeting with the FDA by the end of 2023 and is expecting more data from the Fred Hutch clinical trial to further support MB-106's potential for treating lymphoma in this setting.