AstraZeneca Pharmaceuticals LP issued the following announcement on June 4.
AstraZeneca and MedImmune, its global biologics research and development arm, today presented results from the Phase III (‘1053’) clinical trial that evaluated moxetumomab pasudotox in 80 patients with relapsed or refractory hairy cell leukaemia (HCL) who had received at least two prior lines of therapy.
Moxetumomab pasudotox, an investigational anti-CD22 recombinant immunotoxin, showed a 75% objective response (OR) rate, a 41% complete response (CR) rate, and a 30% durable CR rate (primary endpoint). The majority of patients with a complete response had a durable response (73%; 24/33) and achieved a negative minimal residual disease (MRD) status (82%; 27/33). Findings from this pivotal trial were presented for the first time during an oral session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, USA (Abstract #7004).
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “Moxetumomab pasudotox is an investigational, first-in-class immunotoxin which we believe has the potential to advance outcomes for patients with relapsed or refractory hairy cell leukaemia, a condition with a high unmet need. It is also the first agent to be submitted for regulatory review from our Antibody Drug Conjugates platform, and as such demonstrates our commitment to developing novel treatments for blood cancer.”
Robert J. Kreitman, MD, Senior Investigator, Head of Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, said: “Hairy cell leukaemia is a rare, chronic blood cancer with no established standard of care for patients with relapsed or refractory disease following purine nucleoside analogue therapy. With very few treatments available, there remains significant unmet medical need for people with relapsed or refractory disease. The response rates observed in this trial, and elimination of the residual leukaemia cells that cause relapse in some patients, highlight the potential impact this potential new medicine could have on patients and the management of this disease.”
Summary of key results from the Phase III ‘1053’ single arm, multicentre clinical trial in 80 patients with relapsed or refractory HCL (16.7 months median follow-up), as determined by a blinded independent central review:
|OR rate||75% (60/80)|
|CR rate||41% (33/80)|
|Durable CR rate||30% (24/80)|
|Haematologic remission* (blood count normalisation, HR) rate||80% (64/80)|
|MRD negative status (CR rate with immunohistochemistry MRD negativity)||82% (27/33)|
*Haematologic remission (HR) is defined by: neutrophils > 1.5 x 109 /L, platelets > 100 x 109 /L, haemoglobin > 11 g/dL, no transfusions / growth factors > 4 weeks
The primary endpoint of the trial was durable CR, which is defined as CR with HR for >180 days. The median time to HR was 1 month. MRD refers to the small amounts of cancer cells that may remain after treatment.2 A high rate of negative MRD after therapy may further improve outcomes.3 The median duration of OR and median progression-free survival were not reached.
The most frequent treatment-related adverse events (AEs) were nausea (28%), peripheral oedema (26%), headache (21%), and pyrexia (20%); 8% had infections and 3% had neutropaenia deemed treatment-related. Three patient deaths occurred, none of which were determined to be treatment-related. Treatment-related AEs leading to discontinuation were haemolytic uraemic syndrome (HUS; 4 [5%]), capillary leak syndrome (CLS; 2 [3%]), and increased blood creatinine (2 [3%]). Seven patients (9%) had CLS and seven (9%) had HUS; this includes four (5%) patients who had both CLS and HUS. CLS and HUS were manageable and reversible.
In April 2018, AstraZeneca announced that the US Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) for moxetumomab pasudotox for the treatment of adult patients with HCL who have received at least two prior lines of therapy. The BLA is based on results from the Phase III ‘1053’ clinical trial. The FDA has granted Priority Review status with a Prescription Drug User Fee Act action date set for the third quarter of 2018.
Original source can be found here.