The first patient treated in Mustang Bio‘s Phase 1/2 clinical trial testing its investigational MB-106 therapy for B-cell non-Hodgkin’s lymphoma has achieved a complete response to treatment — meaning that all signs of the cancer have disappeared — the company announced.
The trial is investigating the optimized CAR T-cell therapy in people with non-Hodgkins lymphoma affecting the body’s B-cells, whose cancer has come back or did not respond to previous therapies. CAR T-cell therapies use a patient’s own genetically modified immune cells to fight cancer cells.
Treated for relapsed follicular lymphoma — a slow-growing cancer that originates in the B lymphocytes, or B-cells — this patient received the lowest dose of MB-106 tested. The patient achieved a complete response after four weeks of dosing, with no signs of cytokine release syndrome or neurotoxicity, two side effects that are common in immunotherapies.
Though the clinical trial is ongoing and more data is required before any conclusions are reached, the combined research team at Mustang Bio and the Fred Hutchinson Cancer Research Center (Fred Hutch) are optimistic about the results.
“We are thrilled to announce that we have achieved a complete response in the first [patient] dosed with MB-106 following Mustang and Fred Hutch’s enhancement to the cell process,” Manuel Litchman MD, president and CEO of Mustang, said in a press release.
MB-106 is a kind of immunotherapy in which a patient’s own T-cells — immune cells with the ability to fight cancers — are collected and modified in the lab to produce a man-made receptor, called a chimeric antigen receptor (CAR), that binds to a cancer-specific molecule. The modified CAR T-cells are then expanded to millions in optimal lab conditions, and re-infused into the patient, where they will target and eliminate cancer cells.
The target protein of MB-106 is CD20, found on the surface of healthy B-cells and lymphoma cells. CD20 is the target of multiple investigational and approved lymphoma therapies — including rituximab — but few clinical trials have explored this protein as a target of CAR T-cell therapies.
Mustang and Fred Hutch are now testing MD106, which carries a CD20 antibody that has been optimized to improve T-cell activation upon binding to its predefined target, and to prevent unwanted side effects.
The open-label, dose-escalation Phase 1/2 clinical trial (NCT03277729) is designed to investigate the safety and effectiveness of MB-106 in people with B cell non-Hodgkin’s lymphoma. A total of 30 patients are being recruited for the study at Fred Hutch in Seattle.
Participants enrolled in the study will receive a course of chemotherapy before being dosed with MB106. Chemotherapy is often administered during the CAR-T cell therapy process, as it reduces the likelihood of an immune system response to the reintroduced cells.
The primary goal is to determine the maximum tolerated dose of MB-106. That means patients will receive different amounts of CAR-T cells and will be monitored for any adverse reactions, so as to establish the optimal dose of MB-106.
Secondary goals include assessing the proportion of patients achieving complete remission, the time to disease progression or death, called progression free survival, overall survival, and any adverse reactions. Due to the longevity of CAR T-cell therapy, these measures will be evaluated for up to 15 years after the initial dosage.
Litchman said the results from the first patient are “especially encouraging, since the subject received a dose of only 3.3 x 105 CAR T cells/kg” — the lowest dose tested. However, he cautioned that “additional clinical testing is necessary.”
“We are looking forward to follow-up data, as well as continuing to establish the safety of the therapy, which appears to be well tolerated to date,” Litchman said. “We are excited to work further with Fred Hutch to develop MB-106 and anticipate providing additional clinical results by year end.”
