First Patient Treated in Trial of CD20-Targeted CAR T Cells in B-NHL, CLL

Investigators of a trial for B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukemia (CLL) treated the first patient with the novel autologous chimeric antigen receptor (CAR) T-cell therapy MB-106, according to a press release from Mustang Bio, Inc.¹

This multicenter, open-label, nonrandomized phase 1/2 clinical trial (NCT05360238) is being performed under Mustang Bio’s Investigational New Drug (IND) application for MB-106. The first patient treated in the trial did not experience cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), which are serious adverse events associated with CAR T-cell therapy.

“The first clinical trial under Mustang’s IND is an important milestone in the ongoing development and evaluation of MB-106,” Manuel Litchman, MD, president and chief executive officer of Mustang, said in a statement.

MB-106 was designed in collaboration between Mustang Bio and Fred Hutchinson Cancer Center in Seattle, Washington. A single-center phase 1/2 clinical trial (NCT03277729) conducted at Fred Hutchinson Cancer Center is ongoing and has shown positive efficacy and safety outcomes for MB-106 in patients with hematologic malignancies.

“Data presented at several prestigious medical meetings earlier this year from the initial, ongoing phase 1/2 clinical trial at Fred Hutchinson [Cancer Center] show that MB-106 continues to demonstrate high efficacy and a favorable safety profile across patients with a wide range of hematologic malignancies,” Litchman stated.

The new multicenter trial will enroll an estimated 287 patients at 6 centers in 3 arms targeting those with relapsed/refractory CLL/small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), other B-NHL subtypes including follicular lymphoma (FL), and mantle cell lymphoma (MCL). Patients may have received stem cell therapy or CD19-targeted CAR T-cell therapy.

In phase 1, up to 18 patients will be treated in each of 3 arms, which will escalate dose levels using a 3+3 design independently in each arm. The arms consist of those with aggressive NHL subtypes including DLBCL and MCL, those with indolent NHL including FL, and those with CLL/SLL. The FDA has allowed this trial to begin dose escalation at a higher dose than the initial phase 1/2 trial based on both trials using the same lentiviral vector. Each dose level will be assessed for safety to determine the maximum tolerated dose and the recommended phase 2 dose level (RP2D). The Safety Review Committee will make a safety and tolerability assessment based on the 28-day dose-limiting toxicity observation period.

Up to 71 patients will participant in each arm for the phase 2 dose expansion portion. Specific arms will initially include 20 patients treated at the RP2D; based on the results of the interim analysis, up to 51 patients may be added to each arm. Arm 1 will include those with relapsed/refractory DLBCL, primary mediastinal large B-cell lymphoma, and transformed FL. Arm 2 will include those with relapsed/refractory FL, and an additional basket cohort in Arm 2 includes those with B-cell NHL subtypes such as MCL and others including Waldenstrom macroglobulinemia, for which the FDA granted an Orphan Drug Designation for MB-106. Arm 3 will enroll patients with relapsed/refractory CLL/SLL.

The primary end point of the phase 2 portion is objective response rate, while secondary end points include duration of response, progression-free survival, and overall survival, as well as minimal residual disease for patients with CLL.

“To date, the data from the initial, ongoing clinical trial at Fred Hutchinson [Cancer Center] continue to demonstrate a high rate of complete and durable responses,” said Mazyar Shadman, MD, MPH, study chair, associate professor, and physician at Fred Hutchinson Cancer Center and the University of Washington, in a statement. “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.”

Interim results from the ongoing trial at Fred Hutchinson Cancer Center showed strong efficacy and tolerability for MB-106 in 28 patients. As of September 9, 2022, there was an overall response rate of 96% including a complete response (CR) rate of 75%, with 12 patients having a CR for at least 12 months and 4 with a CR for at least 2 years. Responses appeared to deepen following the initial 28-day assessment. All 3 patients who were previously treated with CD19-targeted CAR T-cell therapy responded to the CD20-targeted MB-106. There was no incidence of grade 3 or higher CRS or ICANS, showing a positive safety profile as an outpatient treatment.

“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,” said Litchman.

_Reference:

_{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. Mustang Bio. October 6, 2022. Accessed October 12, 2022. https://bit.ly/3TlIq8T}