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

A multicenter trial of the CAR T-cell product MB-106 has treated its first patient, Mustang Bio, Inc announced.

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.


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.