Mustang Bio has announced its intention to pursue a phase 1 investigator-sponsored clinical trial for the evaluation of MB-106, an investigational autologous CD20-directed chimeric antigen receptor T-cell (CAR-T) therapy originally developed for the treatment of hematological malignancies, in autoimmune disease.1
The specific autoimmune disease(s) that will be evaluated in the trial is as of yet undetermined, but the company hopes to initiate the trial in Q4 of 2024. Along withFred Hutchinson Cancer Center (Fred Hutch), with which Mustang has previously collaborated on MB-106, the company is currently planning the trial, which will be considered a proof-of-concept study.
MB-106 is currently being evaluated in a multicenter phase 1/2 clinical trial (NCT05360238), sponsored by the company itself, in patients with relapsed/refractory B-cell nonHodgkin lymphomas or chronic lymphocytic leukemia. Mustang also has plans to carry out a registrational study for MB-106 in Waldenstrom macroglobulinemia and noted it anticipates enrollment of the first patient in that study in the second half of 2024.
“Mustang is leveraging its expertise in developing cell therapies to explore a new frontier in patient care,” Manuel Litchman, MD, the president and chief executive officer of Mustang, said in a statement.1 “MB-106’s observed safety profile, encouraging efficacy data, and our robust manufacturing capabilities have the potential to translate to improved outcomes for patients with autoimmune diseases. We believe an investigator-sponsored clinical trial is the fastest and most cost-effective way to embark on this program and aim to enroll the first patient in a phase 1 trial in the fourth quarter of this year to demonstrate clinical proof-of-concept. We are in discussions with Fred Hutch to determine the autoimmune indication(s) we plan to pursue in the first trial and look forward to sharing more details in the near future.”
Key Takeaways
- Mustang Bio has announced its intention to pursue a phase 1 investigator-sponsored clinical trial for the evaluation of MB-106, an investigational autologous CD20-directed chimeric antigen receptor T-cell (CAR-T) therapy originally developed for the treatment of hematological malignancies, in autoimmune disease.
- The specific autoimmune disease(s) that will be evaluated in the trial is as of yet undetermined, but the company hopes to initiate the trial in Q4 of 2024.
- MB-106 is currently being evaluated in a multicenter phase 1/2 clinical trial (NCT05360238), sponsored by the company itself, in patients with relapsed/refractory B-cell nonHodgkin lymphomas or chronic lymphocytic leukemia.
Mazyar Shadman, MD, MPH, associate professor, clinical research division, and attending physician, hematologic malignancies, Fred Hutch, and associate professor, medical oncology division, University of Washington School of Medicine, presented data from the phase 1/2 trial in B-NHL at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.2 MB-106 yielded responses with a number of complete responses (CRs) and displayed CAR-T persistence in 3 patients with relapsed/refractory indolent non-Hodgkin lymphomas successfully treated (1 received non-conforming material). Furthermore, 2 patients with follicular lymphoma had CRs and 1 with Waldenström macroglobulinemia had a very good partial response. The safety profile in the participants treated was characterized as favorable, with no cases of grade 3 or grade 4 cytokine release syndrome and no cases of immune effector cell-associated neurotoxicity syndrome reported.
“Data from the MB-106 phase 1/2 multicenter trial presented at the recent 65th ASH Annual Meeting demonstrate strong clinical activity and a favorable safety profile, establishing feasibility of outpatient administration and building a foundation for the treatment of autoimmune diseases, where tolerance for the more severe toxicities observed with approved CAR-Ts is lower,” Litchman continued.1 “Mustang believes MB-106 has the potential to bring personalized CAR T-cell therapy to a broader patient population through the expansion of indications and accessibility.”
Although many companies are currently evaluating CD19-directed CAR-T therapies for the treatment of autoimmune disease, Mustang is not the only company seeking to treat autoimmune disease with a CD20-directed CAR-T therapy. In August 2023, ImmPACT Bio’s IMPT-514, an investigational bispecific CD19/CD20-directed CAR-T therapy, received clearance of an investigational new drug (IND) application from the FDA for a clinical trial in patients with active, refractory systemic lupus erythematosus (SLE).3 Notably, in the same month, Artiva Biotherapeutics’ AlloNK (AB-101), an investigational allogeneic natural killer cell therapy, also received clearance of an IND application from the FDA to be evaluated in a clinical trial as part of a combination therapy with antiCD20 monoclonal antibody rituximab in patients with SLE and active lupus nephritis.4
REFERENCES
1. Mustang Bio announces vision for CAR t-cell therapy platform expansion into autoimmune diseases. News release. Mustang Bio, Inc. March 28, 2024. Accessed April 16, 2024. https://ir.mustangbio.com/news-events/press-releases/detail/177/mustang-bio-announces-vision-for-car-t-cell-therapy
2. Shadman M, Caimi PF, O’Brien SM, et al. Efficacy and Safety of a Third Generation CD20 CAR-T (MB-106) for Treatment of Relapsed/Refractory Indolent B-Cell Non-Hodgkin Lymphoma: Phase-1 Results from a Multicenter Trial. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract #2102
3. ImmPACT Bio announces FDA clearance of IND application for bispecific CD19/CD20 CAR T therapy IMPT-514 for the treatment of refractory systemic lupus erythematosus. News release. ImmPACT Bio USA, Inc. August 15, 2023. Accessed August 16, 2023. https://immpact-bio.com/news-and-events/immpact-bio-announces-fda-clearance-of-ind-application-for-bispecific-cd19-cd20-car-t-therapy-impt-514-for-the-treatment-of-refractory-systemic-lupus-erythematosus/
4. Artiva Biotherapeutics announces FDA clearance of IND for AlloNK cell therapy candidate in combination with rituximab in lupus nephritis. News release. Artiva Biotherapeutics, Inc. August 16, 2023. Accessed August 18, 2023. https://www.artivabio.com/artiva-biotherapeutics-announces-fda-clearance-of-ind-for-allonk-cell-therapy-candidate-in-combination-with-rituximab-in-lupus-nephritis/
