On June 2, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported that results from the Phase III (‘1053’) clinical trial (Abstract #7004) that evaluated moxetumomab pasudotox in 80 patients with relapsed or refractory hairy cell leukemia (HCL) who had received at least two prior lines of therapy.1 (Press release, AstraZeneca, JUN 2, 2018, View Source [SID1234527107])

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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) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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 leukemia, 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 leukemia is a rare, chronic blood cancer with no established standard of care for patients with relapsed or refractory disease following purine nucleoside analog 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 leukemia 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, multicenter clinical trial in 80 patients with relapsed or refractory HCL (16.7 months median follow-up), as determined by a blinded independent central review:

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 edema (26%), headache (21%), and pyrexia (20%); 8% had infections and 3% had neutropenia deemed treatment-related. Three patient deaths occurred, none of which were determined to be treatment-related. Treatment-related AEs leading to discontinuation were hemolytic uremic 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.

NOTES TO EDITORS

About Moxetumomab Pasudotox

Moxetumomab pasudotox (formerly CAT-8015 or HA22) is an investigational anti-CD22 recombinant immunotoxin and a potential new medicine with the opportunity to be a first-in-class treatment in the US for patients with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior lines of therapy. Immunotoxins are a class of anticancer agents that combine the selectivity of antibodies to target drug delivery and the potency of toxins to kill target cancer cells.4 Moxetumomab pasudotox is composed of a binding portion of an anti-CD22 antibody fused to a toxin. CD22 is a B-lymphocyte restricted transmembrane protein with a higher receptor density in HCL cells relative to normal B cells, making it an attractive therapeutic target for the treatment of this cancer.5 After binding to CD22, the molecule is internalized, processed and releases its modified protein toxin that inhibits protein synthesis, leading to apoptotic cell death. Moxetumomab pasudotox has been granted Orphan Drug Designation by the FDA for the treatment of HCL.

About Hairy Cell Leukemia

HCL is a rare, incurable slow-growing leukemia in which the bone marrow overproduces abnormal B cells or lymphocytes.6 HCL can result in serious and life-threatening conditions, including infections, bleeding and anemia.7 Approximately 1,000 people are diagnosed with HCL in the US each year.8,9,10 While many patients initially respond to treatment, up to 40% will relapse.11 With no established standard of care and very few treatments available, there remains significant unmet medical need for people with relapsed or refractory HCL.12,13

About the ‘1053’ Phase III Trial

The ‘1053’ trial is a single-arm, multicenter Phase III clinical trial assessing the efficacy, safety, immunogenicity and pharmacokinetics of moxetumomab pasudotox monotherapy in patients with relapsed or refractory HCL who have received at least two prior therapies. The trial is being conducted in 80 patients across 34 sites in 14 countries.14 The primary endpoint was durable complete response (CR), defined as CR with hematologic remission (blood count normalization) for >180 days. Secondary outcome measures included overall response rate, relapse free survival, progression-free survival, time to response, safety, pharmacokinetic and immunogenic potential.14