First Patient With B-NHL or CLL Treated With MB-106 in Phase 1/2 Study

The phase 1/2 clinical trial of MB-106 is demonstrating high efficacy, durable responses, and a favorable safety profile as the first patient treated did not experience cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome

The first patient has been treated in the phase 1/2 clinical trial (NCT05360238) evaluating the safety and efficacy of MB-106 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) and chronic lymphocytic leukemia (CLL), according to Mustang Bio, Inc.1

MB-106 is a CD20-targeted, autologous chimeric antigen receptor (CAR) T-cell therapy. The agent, which was developed by researchers at the Fred Hutchinson Cancer Research Center (Fred Hutc), is a third-generation CAR derived from a fully human antibody.

The patient treated with MB-106 did not experience cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), leading the ongoing clinical trial of MB-106 to continue to elicit high efficacy, durable responses, and a favorable safety profile across wide range of hematologic malignancies.

“The first clinical trial under Mustang’s investigational new drug application 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,” said Manuel Litchman, MD, president and chief executive officer of Mustang Bio, Inc, in the press release, 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.”

The multicenter, open-label, non-randomized, phase 1/2 study aims to evaluate the safety, tolerability, and efficacy of MB-106 in patients with relapsed or refractory B-NHL or CLL.2 However, the study is open to patients with a variety of selected CD20-expressing malignancies, including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL).

Part 1 of the study will enroll approximately 287 patients with aggressive B-NHL, including DLBCL, and MCL, as well as patients with indolent NHL like FLL. Patients with CLL of small lymphocytic lymphoma (SLL) will also be evaluated in this portion of the trial.

The phase 1 part of the study will administer patients escalating doses of MB-106 in a 3 + 3 study design. The coprimary end points are the incidence of treatment-emergent adverse events (TEAEs) in patients with relapsed or refractory CD20-positive B-NHL or CLL and to determine the recommended phase 2 dose of the agent. Secondary end points for phase 1 are ORR, duration of response (DOR), and minimal residual disease (MRD) in patients with CLL.

In the phase 2 portion of the study, patients with relapsed/refractory DLBCL, including those with MYC, BCL2, BCL6 rearrangement and primary mediastinal large B-cell lymphoma or transformed FL will be enrolled. Patients with B-NHL subtypes that progressed after available therapy, including MCL, marginal zone lymphoma, Waldenstrom macroglobulinemia, Burkitt-like lymphoma, hairy cell leukemia, and CLL/SLL will also be included.

For phase 2, the primary end point of the study is ORR with the secondary end points of DOR, the incidence of TEAEs, and the total number of patients with MRD in CLL.

Patients aged 18 years and older are eligible to enroll in the trial if they have relapsed after treatment with CD19 CAR-T cell therapy, have an ECOG performance status of 0-1, a life expectancy of ≥ 16 weeks, meet all laboratory criteria, adequate pulmonary function, and have left ventricular ejection fraction ≥ 50%. Further, all patients must be capable of consenting to treatment and be able to follow the visit scheduled and other protocol requirements. Female patients of childbearing potential must provide a negative pregnancy test, and patients of all genders must agree to use contraception for the duration of study.

Interim data from the initial 28 patients treated in the ongoing multicenter, open-label, non-randomized, phase 1/2 clinical trial continue to support the use of MB-106 in B-NHLs and CLL.

Interim data as of September 9, 2022, show the agent to elicit an overall response rate (ORR) of 96% and complete response (CR) rate of 75% in heatologic malignancies, including follicular lymphoma, CLL, diffuse large B-cell lymphoma, and Waldenstrom macroglobulinemia

A total of 12 patients have experienced CR for more than 12 months with 10 ongoing and 4 patients have had a CR for more than 2 years. The longest CR currently seen in a patient in the trial is 33 months. Further, 6 patients had a partial response which improved to a CR. All of these patients remain in ongoing CR. Among the 3 patients previously treated with CD19 CAR T-cell therapy, all have responded to treatment with MB-106.

Regarding safety, MB-106 has shown a favorable safety profile as an outpatient therapy so far with no patients having grade 3 or higher CRS or ICANS. CAR T-cell persistence results in deepening responses following initial 28-day assessments.

Enrollment in this clinical trial of MB-106 is ongoing and data from the study is expected to be released at the end of 2022.

“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,” said Mazyar Shadman, MD, MPH, study chair, associate professor and physician at Fred Hutch and University of Washington, in the press release. “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.”

References:
1. Mustang Bio announces first patient treated in Its multicenter phase 1/2 clinical trial of MB-106, a first-in-class CD20-targeted, autologous CAR T Cell therapy to treat B-cell non-hodgkin lymphoma and chronic lymphocytic leukemia. News release. Mustang Bio, Inc. October 6, 2022. Accessed October 10, 2022. https://bit.ly/3fT2S2k
2. Study to assess safety, tolerability and efficacy of mb-106 in patients with relapsed or refractory B-cell NHL or CLL. ClinicalTrials.gov. Updated August 19, 2022. Accessed October 10, 2022. https://bit.ly/3QKGlm8