IND for CD20-Targeted CAR T-cell Therapy Is Accepted by FDA for R/R CLL

An investigational new drug (IND) application for the CD20-targeted chimeric antigen receptor (CAR) T-cell therapy MB-106 was recently accepted by the FDA to initiate a phase 1/2 multicenter trial in patients with relapsed or refractory CD20-positive chronic lymphocytic leukemia (CLL), announced the company responsible for developing the therapy, Mustang Bio, Inc.¹

MB-106 is an autologous therapy made up of a third-generation CAR developed from a fully human antibody. It targets CD20, a validated membrane-embedded surface molecule expressed by cancer cells.² Currently, CAR T-cell therapies targeting CD20 are lacking in this setting.

In addition, the application also included the treatment of patients with relapsed/refractory CD20-positive B-cell non-Hodgkin lymphoma (B-NHL). The trial will assess safety, tolerability, and efficacy of MB-106 and is expected to start enrolling patients in the third quarter of 2021.

“We are pleased with the FDA’s acceptance of our IND application for MB-106, which allows us to further advance this CAR T[-cell] therapy as a potentially safe and effective treatment option for B-NHL and CLL. It is especially gratifying that we were able to achieve this milestone in just 28 days after our IND submission,” Manuel Litchman, MD, President and Chief Executive Officer of Mustang Bio, Inc, said in a press release. “We are committed to finding better treatment options for patients living with these cancers and look forward to initiating our multicenter, phase 1/2 clinical trial later this year, with [Mazya Shadman, MD, MPH] as the Study Chair.”

At the 2021 American Society of Hematology Annual Meeting and Exposition, Shadman, who is an associate professor in the Clinical Research Division at the Fred Hutchinson Cancer Research Center, presented findings from an ongoing phase 1/2 clinical trial of MB-106 in patients with B-NHL (NCT03277729). The trial was later modified to include patients with CLL.

To be included in the ongoing trial, patients with CLL must have relapsed after or had no response to prior therapy. Evidence of CD20 expression by immunohistochemistry or flow cytometry is required on tumor specimens obtained with biopsy on screening.

Patients receive leukapheresis and may undergo bridging therapy as needed for disease control. Then, patients receive intravenous (IV) cyclophosphamide and may also receive IV fludarabine. After 36 to 96 hours, patients receive CAR T-cell therapy infusion over a 20 to 30 minute period. Dose levels 1 through 3 involve 3.3 × 10⁵ CAR-positive T-cells/kg, 1 × 10⁶ CAR-positive T-cells/kg, and 3.3 × 10⁶ CAR-positive T-cells/kg, respectively.

Of note, the safety profile of the therapy in patients with B-NHL at a 28-day evaluation was favorable, with only 2 of 16 patients reporting cytokine release syndrome and no patients having immune effector cell-associated neurotoxicity syndrome. One grade 3 event of unexplained alkaline phosphatase elevation in the setting of fever was reported.

References

1. Mustang Bio Announces FDA Acceptance of IND Application for MB-106, a CD20-Targeted CAR T Therapy. News release. Mustang Bio, Inc. May 10, 2021. Accessed May 11, 2021. https://bit.ly/3uFzajN

2. Mustang Bio Announces Interim Phase 1/2 Data for MB-106 in Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma. News release. Mustang Bio, Inc. December 7, 2020. Accessed May 11, 2021. https://bit.ly/3tEly72