Data from the first 2 patients were presented at the IWWM 2022 meeting.
MB-106, Mustang Bio’s chimeric antigen receptor (CAR) T-cell therapy, has yielded a 100% overall response rate in 2 patients with Waldenstrom Macroglobulinemia (WM) treated so far in an ongoing phase 1/2 trial (NCT03277729).1
These data were presented at the 11th International Workshop for Waldenstrom's Macroglobulinemia (IWWM-11) taking place in Madrid, Spain, on October 29, by Mazyar Shadman, MD, MPH, associate professor, clinical research division, Fred Hutch Cancer Center.
“We are very pleased with the advancement of the MB-106 clinical program which includes the recently announced multicenter, open-label, non-randomized Phase 1/2 clinical trial evaluating its safety and efficacy, the first MB-106 clinical trial under Mustang’s Investigational New Drug Application. Additionally, we are grateful that the Fred Hutch team continues to present compelling data from its ongoing Phase 1/2 clinical trial that demonstrate high efficacy and a favorable safety profile across chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphomas (B-NHLs) including WM, a rare form of this cancer,” Manuel Litchman, MD, president and chief executive officer, Mustang Bio, said in a staetement.2 “Finally, having been granted Orphan Drug Designation by the FDA for WM, we are looking forward to treating additional WM patients in the Mustang-sponsored Phase 1 portion of our trial in order to support a fast-to-market Phase 2 strategy for this indication.”
MB-106 is an autologous, third generation, CD20-targeted lentiviral CAR T-cell therapy being evaluated in ths phase 1/2 in 4 dose levels (1 x 105, 3.3 x 105, 1 x 106, 3.3 x 106, and 1 x 107 cells/kg) for the treatment of previously treated WM, third-line large cell lymphoma, second-line follicular lymphoma (FL) and mantle cell lymphoma (MCL), CLL after BTK inhibitors or venetoclax failure, and other previously treated B-NHLs.1 Patients are allowed to have previous CD19 CAR T-cell treatment.
The 2 participants in the WM cohort were a 71-year-old and a 59-year-old man, both treated at dose level 3 of 3.3x106 cells/kg with good evidence of CAR-T persistence after infusion. Both participants experienced grade 1 cytokine release syndrome while the older man also experienced grade 1 immune effector cell-associated neurotoxicity syndrome. The older man remains in remission as of 15 months after MB-106 treatment while the younger man passed away from complications of COVID-19 6 months after MB-106 treatment with no evidence of disease progression. In addition to the patients with WM, Shadman presented ongoing data from other patients in the study, including 8 of 19 patients with FL who continue to have an ongoing complete response.
MB-106 received orphan drug designation from the FDA in June 2022. Mustang Bio is expanding the phase 1/2 trial into a multicenter phase 2 trial that will build on the initial 6 US sites into 20 US sites for up to 71 patients (an initial 20 with the possibility of enrolling up to an additional 51) each in 3 arms. Patients will be treated at the respective recommended phase 2 dose for each arm. The study is currently enrolling and dosed its first patient in October 2022.
“A CAR-T option for WM should meet high safety and efficacy standards. [These data demonstrate] limited but promising experience from MB-106. WM is one of the priority diseases for MB-106 development,” Shadman concluded his presentation.