Amgen Seeks FDA Approval for Blinatumomab in ALL

A Biologics License Application has been submitted to the FDA for the bispecific T-cell engager (BiTE) antibody blinatumomab as a treatment for adult patients with Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL)

Anthony S. Stein, MD

A Biologics License Application has been submitted to the FDA for the bispecific T-cell engager (BiTE) antibody blinatumomab as a treatment for adult patients with Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), according to an announcement by Amgen, the company developing the drug.

In July 2014, the FDA granted blinatumomab a breakthrough therapy designation for the treatment of adult patients with ALL. Both the submission and the breakthrough designation were based on data from a phase II trial of 189 patients. According to results presented at the 2014 ASCO Annual Meeting, 43% (n = 82) of patients achieved a complete remission (CR) or CR with partial hematological recovery (CRh), with 80% of responses occurring within the first cycle.

"Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL," Anthony S. Stein, MD, clinical professor of Hematology/Oncology at City of Hope, said in a statement. "Blinatumomab has the potential to significantly advance treatment options for patients living with this difficult-to-treat disease, and the BLA submission marks an important step toward achieving this goal."

In the phase II study that was the basis for the submission, intravenous blinatumomab was administered for 4 weeks followed by a 2-week resting period for up to 5 cycles. The median age of patients was 39. The primary endpoint of the study was CR or CR with CRh. Secondary endpoints included CR, CRh, relapse-free survival, and overall survival (OS).

For the entire population, the rate of CR/CRh was 43% (95% CI, 36%-51%), which included a CR rate of 34%. In patients who had not received prior allogeneic hematopoietic stem-cell transplantation, the CR/CRh rate was 47%. The CR/CRh rates were 40%, 51%, and 34% for patients treated with no therapies, 1 prior therapy, and greater than 2 therapies, respectively.

The median relapse-free survival was 5.9 months (95% CI, 5.0-8.4). The median OS was 6.1 months (95% CI, 4.2-7.5). A total of 74% of patients were minimal residual disease responders.

The most common all-grade adverse events were pyrexia (59%), headache (35%), and febrile neutropenia (29%). The most common grade 3/4 adverse events were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). In all, 3 patients experienced treatment-related grade 5 adverse events: sepsis (n = 2) and candida infection (n = 1).

"We look forward to working with regulatory authorities to make blinatumomab available for adult patients with acute lymphoblastic leukemia, who experience high relapse rates and have limited treatment options," Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a statement. "The filing for blinatumomab brings us a step closer to first realizing the potential of BiTE technology and represents our commitment to evaluating this novel approach in a broad range of difficult-to-treat cancers."

An open-label phase III study comparing blinatumomab with chemotherapy is currently enrolling patients with relapsed or refractory B-precursor ALL. In the trial, patients will be randomized in a 2:1 ratio to receive blinatumomab or treatment with investigator choice of 1 of 4 protocol defined chemotherapy regimens. The primary endpoint of this study is overall survival.