Interim data from an ongoing study demonstrate continuing efficacy in B-NHL, CLL, and FL.
A phase 1/2 clinical trial (NCT05360238) has dosed its first patient with MB-106 (Mustang Bio), a chimeric antigen receptor (CAR) T-cell therapy for the treatment of relapsed or refractory B-cell non-Hodgkin lymphomas (B-NHL) and chronic lymphocytic leukemia (CLL).
The patient did not experience cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). The trial is a multicenter, open-label trial that builds on the ongoing trial at Fred Hutchinson Cancer Center under the same investigational new drug application (IND). It is evaluating the safety and efficacy of MB-106, a first-in-class CD20-targeted, autologous CAR T cell therapy.
“The first clinical trial under Mustang’s IND is an important milestone in the ongoing development and evaluation of MB-106. Data presented at several prestigious medical meetings earlier this year from the initial, ongoing Phase 1/2 clinical trial at Fred Hutch show that MB-106 continues to demonstrate high efficacy and a favorable safety profile across patients with a wide range of hematologic malignancies. We look forward to providing updates on our multicenter MB-106 clinical trial as it progresses and anticipate reporting efficacy data in the fourth quarter of this year,” Manuel Litchman, MD, president and chief executive officer, Mustang, said, in a statement.
Recent interim data, as of September 9, 2022, from 28 patients treated in the ongoing, investigator-sponsored study, have continued to support MB-106's benefit. No patients experienced CRS or ICANS greater than grade 3. Overall response rate is 96% and complete response (CR) rate is 75% in patients with follicular lymphoma, CLL, diffuse large B-cell lymphoma, and Waldenstrom macroglobulinemia.
Twelve patients had a CR for over 12 months with 10 CRs still ongoing. The longest CR is 33 months, and 4 patients had a CR for over 2 years. Six patients with a partial response (PR) improved to ongoing CRs. Three patients had been previously treated with CD19 CAR T-cell therapy and all responded. Investigators also found that CAR-T persistence resulted in deepening responses after the initial 28-day assessment.
“We are excited to broaden the evaluation of MB-106 with this multicenter clinical trial under Mustang’s IND. To date, the data from the initial, ongoing clinical trial at Fred Hutch continue to demonstrate a high rate of complete and durable responses,” Mazyar Shadman, MD, MPH, study chair, associate professor and physician, Fred Hutch and University of Washington, added to the statement. “In addition, MB-106 has shown potential to treat patients in an outpatient setting and provide another immunotherapy option for patients treated previously with CD19-directed CAR T cell therapy.”
The trial is aiming to enroll 287 patients with CLL and B-NHLs, including mantle cell lymphoma. Patients must have evidence of CD20 expression. Phase 1 of the trial will assess escalating dose levels of MB-106 in a 3+3 design in 3 arms. Each arm will have up to 18 patients, with 6 at the maximum tolerated dose. The Safety Review Committee will assess 28-day data and the recommended phase 2 dose will be established. In the phase 2 portion, a total of 71 patients will participate with up to 20 patients in each arm. Up to an additional 51 patients may be added to each arm after an interim analysis.