MB-106, a first-in-class, CD20-targeted autologous CAR T-cell therapy, led to durable clinical responses with low-grade cytokine release syndrome in patients with indolent lymphoma.
MB-106, a first-in-class, CD20-targeted autologous CAR T-cell therapy, led to durable clinical responses with low-grade cytokine release syndrome (CRS) in patients with indolent lymphoma, according to topline data from an ongoing, industry-sponsored phase 1/2 trial (NCT05360238) being conducted in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) and chronic lymphocytic leukemia (CLL).1
Results from the multicenter trial demonstrated that all 4 patients with relapsed/refractory indolent NHL treated at the starting dose of 3.3 x 106 CAR T cells/kg experienced clinical response, with CAR T cells persisting for at least 6 months.
Two patients with follicular lymphoma, 1 of whom had been previously treated with a CD19-directed CAR T-cell therapy, experienced complete response (CR) by PET-CT and bone marrow.
The third patient with Waldenström macroglobulinemia who had received 9 prior treatments and had high disease burden experienced complete metabolic response by PET-CT, morphologic clearance of lymphoma in bone marrow, and resolution of the IgM monoclonal protein. In June 2022, the FDA granted orphan drug designation to MB-106 for the treatment of patients with Waldenstrom macroglobulinemia.2
The fourth patient who enrolled with heavily transfusion dependent hairy cell leukemia continued to show evidence of stable disease with decreased disease in bone marrow, with prolonged transfusion independence at 6 months.
Regarding safety, only 1 case of grade 1 CRS was reported. Based on these data, the safety review committee approved dose escalation to 1.0 x 107 CAR T cells/kg.
“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. 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,” Manuel Litchman, MD, president and chief executive officer of Mustang, said in a news release.
In October 2022, the company announced that the first patient had been treated in the industry-sponsored trial, demonstrating no evidence of CRS or immune effector cell–associated neurotoxicity syndrome (ICANS).3
Interim data from the original, investigator-initiated phase 1/2 trial (NCT03277729), first presented at the 2020 ASH Annual Meeting, demonstrated favorable safety data and preliminary activity with MB-106 in patients with follicular lymphoma and mantle cell lymphoma (MCL).4 Findings from the interim analysis showed an overall response rate (ORR) of 96% and CR rate of 75% among 28 patients with B-NHL.3
Additional data from the phase 1/2 trial (NCT03277729) were presented by study chair, Mazyar Shadman, MD, MPH, associate professor and physician at Fred Hutchinson Cancer Center and the University of Washington, at the 5th International Workshop on CAR T and Immunotherapies.1
Results from the follicular lymphoma cohort (n = 20) demonstrated an ORR of 95%, with a CR rate of 80%, and a partial response rate of 15%. Shadman reported durable responses in responders, with 10 patients experiencing CR for more than 10 months, 4 patients experiencing CR for more than 2 years, and 1 patient sustaining CR for more than 3 years. Notably, 1 patient who achieved CR had been previously treated with a CD19-directed CAR T-cell therapy. Of the 6 patients who experienced CRS, only 1 had a grade 2 event.
In the Waldenström macroglobulinemia cohort (n = 6), all of whom had received prior BTK inhibitors, 2 patients experienced CR, 1 of whom remained in CR after 22 months, and no patients have required subsequent therapy due to progression. No cases of grade 3 or greater CRS or ICANS were reported.
Subsequent data from the trial, which were presented at the 2023 EHA Congress, further confirmed the activity of MB-106 in patients with BTK-refractory Waldenstrom macroglobulinemia.5
The industry-sponsored, 3-arm clinical trial, now open at 5 centers, is enrolling patients with CLL and B-NHL, including follicular lymphoma and Waldenström macroglobulinemia, diffuse large B-cell lymphoma, and MCL. A sixth center is anticipated by the end of 2023. The trial is using the same lentiviral vector as the Fred Hutch–sponsored, single-center trial.1
To be eligible for enrollment, patients must have relapsed disease following treatment with CD19-directed CAR T-cell therapy. Patients will be assigned to 1 of 3 arms in which they will receive escalating doses of MB-106 using a 3+3 design.
Per the study design, up to 18 patients will be treated in each phase 1 arm, including 6 patients at the maximum tolerated dose (MTD) in each arm. Safety of each dose level will be evaluated during the 28-day dose-limiting toxicity observation period until the MTD has been reached and the recommended phase 2 dose (RP2D) has been established in each arm.
In phase 2, selected patients with relapsed/refractory CD20-positive B-cell malignancies will be treated with MB-106 at the RP2D for each arm. Patients with Waldenström macroglobulinemia and DLBCL relapsed from prior CD19-directed CAR T-cell therapy will be prioritized. Each arm will enroll up to 20 patients; an additional 51 patients may be added to each arm based on interim data from each arm.
Findings from the phase 1 Waldenström macroglobulinemia cohort will be used to back a fast-to-market phase 2 strategy for this indication, according to the company, who added that the first patient with Waldenström macroglobulinemia is expected be dosed in the pivotal phase 2 trial by mid-2024. The company plans to solidify this strategy at an end-of-phase 1 meeting with the FDA at the end of 2023, and by 2024, expects to have applied for regenerative medicine advanced therapy designation from the FDA for Waldenström macroglobulinemia.
“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,” Shadman, said. “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.”