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The FDA has assigned a priority review designation to blinatumomab as a treatment for adult patients with Philadelphia chromosome-negative relapsed/refractory B-precursor acute lymphoblastic leukemia.
Sean E. Harper, MD
The FDA has assigned a priority review designation to blinatumomab as a treatment for adult patients with Philadelphia chromosome-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), according to Amgen, the company developing the immunotherapy.
Through the priority review program, the FDA plans to make a decision on the Biologics License Application for the investigational bispecific T cell engager (BiTE) antibody within 6 months, placing the decision date on May 19, 2015. The priority review follows a breakthrough therapy designation from the FDA in July 2014.
"The FDA's acceptance of our BLA submission and designation of priority review for blinatumomab underscores the need to provide new treatment approaches for adult patients with relapsed or refractory ALL, and we are encouraged by the Agency's expedited review," Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a press release.
Blinatumomab is a recombinant, single-chain monoclonal antibody that possesses antigen-recognition sites for CD3 and CD19. The CD3 complex consists of T cell surface glycoproteins, while CD19 is a tumor-associated antigen. The combination of these recognition sites into one therapy is thought to promote cytotoxic T lymphocyte and helper T lymphocyte activity against CD19-expressing B-lymphocytes.
Given its mechanism of action, the drug holds potential across a variety of B-cell malignancies. As a result, in February 2006 the FDA granted blinatumomab an orphan drug designation as a treatment for types of indolent B cell lymphoma, ALL, and chronic lymphocytic leukemia. At this time, Micromet was developing blinatumomab, labeled MT103; however, upon acquiring this company in 2012, Amgen accelerated exploration into the novel immunotherapy.
In supporting data for the priority review, which was presented at the 2014 ASCO Annual Meeting, 43% of patients treated with blinatumomab achieved a complete remission (CR) or CR with partial hematological recovery (CRh), with 80% of responses occurring within the first cycle. In patients with bone marrow blast in the range of 25% to 50% (n = 31), the CR/CRh rate was 77%.
"Blinatumomab has the potential to make a significant impact for these patients, and this milestone, along with other ongoing filings around the world, represents the potential of BiTE technology in cancers that are challenging to treat," Harper said.
In the phase II study that was the basis for the expedited review, intravenous blinatumomab was administered for 4 weeks followed by a 2-week resting period for up to 5 cycles to 189 patients with Ph- ALL. 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).
Across all patient populations, the CR rate was 34%. The CR/CRh rate was 42% in patients who had not received prior allogeneic hematopoietic stem-cell transplantation compared with 45% in those who had. The CR/CRh rates were 50%, 47%, 36%, and 34% for patients treated with no prior salvage therapies, 1 prior therapy, 2 prior therapies, and 3 or more therapies, respectively.
The median relapse-free survival was 5.9 months with blinatumomab (95% CI, 4.8-8.3). 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 (25%), neutropenia (16%), and anemia (14%). In all, 3 patients experienced treatment-related grade 5 adverse events: sepsis (n = 2) and candida infection (n = 1).
An open-label phase III study comparing blinatumomab with chemotherapy is currently enrolling patients with relapsed or refractory B-precursor ALL. In this 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.