MB-106 Garners Responses, Favorable Safety in R/R B-Cell Non-Hodgkin Lymphoma

The FDA accepted an investigational new drug application for MB-106 in the management of relapsed/refractory CD20-positive CLL in May 2021.

Treatment with the investigational autologous CAR T-cell therapy MB-106 appeared to be effective and tolerable in patients with relapsed/refractory indolent non-Hodgkin lymphoma, according to a press release on initial data from an indolent lymphoma cohort of a phase 1/2 study (NCT05360238).¹

Investigators observed clinical responses among 4 patients receiving a starting dose of 3.3x10⁶ CAR T cells/kg, which included 2 with follicular lymphoma who experienced a complete response (CR) as confirmed by PET CT and bone marrow. Additionally, another patient with Waldenstrom macroglobulinemia and high disease burden who received 9 prior lines of therapy experienced a complete metabolic response, morphologic clearance of lymphoma in bone marrow, and had their IgM monoclonal protein resolved. A fourth patient with hairy cell leukemia and transfusion dependency also achieved stable disease with decreased bone marrow disease plus complete transfusion independence that has been ongoing for more than 6 months.

The data also highlighted persistence of CAR T cells at more than 6 months, and investigators have only reported grade 1 cytokine release syndrome (CRS) to date. The Safety Review Committee had collectively agreed upon an escalated dose of 1.0x10⁷ CAR T cells/kg following treatment of the 4 patients with indolent non-Hodgkin lymphoma.

“Overall, MB-106 continues to exhibit high efficacy and a favorable safety profile compared [with] currently approved autologous CAR-Ts,” Manuel Litchman, MD, president and chief executive officer at Mustang Bio, Inc, said in the press release. “We expect to provide an additional update on dose escalation and report response data at a major medical meeting later this year.”

Initial findings from the multi-center trial appeared to be consistent with data from an ongoing phase 1/2 trial assessing MB-106 at Fred Hutchinson Cancer Center (Fred Hutch). In a cohort of patients with follicular lymphoma (n = 20) in the Fred Hutch trial, MB-106 produced an overall response rate (ORR) of 95%, which included CRs in 80% and partial responses (PRs) in 15%. Additionally, 10 patients had an ongoing CR for more than 10 months, 4 had an ongoing CR for more than 2 years, and another experienced a CR that has been sustained for more than 3 years. Overall, 6 patients had CRS, including 1 with grade 2 CRS.

Among 6 patients with Waldenstrom macroglobulinemia with receipt of prior Bruton tyrosine kinase inhibitors in the Fred Hutch trial, 2 had a CR, including 1 with a sustained response beyond 22 months. There were no grade 3 or higher instances of CRS or immune effector cell-associated neurotoxicity syndrome; none of the treated patients needed to initiate new therapy.

“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,” Mazyar Shadman, MD, MPH, study chair, associate professor, and physician at Fred Hutch and University of Washington, said while presenting data at the 5th International Workshop on CAR-T and Immunotherapies.

In the 3-arm phase 1/2 trial, investigators are assessing MB-106 across 5 centers as a treatment for patients with B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL). Up to 18 patients will receive treatment in each phase 1 arm.

The trial’s primary end points include safety, tolerability, and the recommended phase 2 dose in phase 1 as well as ORR per Lugano Classification for Lymphomas in phase 2. Secondary end points include duration of response, progression-free survival, and overall survival.

The FDA accepted an investigational new drug application for MB-106 in the management of relapsed/refractory CD20-positive CLL in May 2021.²

References

1. Mustang Bio announces first data from ongoing multicenter phase 1/2 clinical trial evaluating MB-106 CAR-T cell therapy. News release. Mustang Bio, Inc. August 16, 2023. Accessed August 18, 2023. https://shorturl.at/iryBI
2. Mustang Bio announces FDA acceptance of IND application for MB-106, a CD20-targeted CAR T Therapy. News release. Mustang Bio, Inc. May 10, 2021. Accessed August 18, 2023. https://bit.ly/3uFzajN