AstraZeneca announced that three of its cancer compounds— moxetumomab pasudotox, olaparib and selumetinib—will be moving forward to Phase III clinical development. Oncology is one of the company’s core therapy areas and accelerating the development of a number of new molecular entities in its pipeline is a strategic priority.
The first patient has been enrolled in a Phase III trial evaluating moxetumomab pasudotox in adult patients with hairy cell leukaemia who have not responded to or relapsed after standard therapy. The trial is sponsored by the Cancer Therapy Evaluation Program (CTEP), a program within the Division of Cancer Treatment and Diagnosis at the US National Cancer Institute. Moxetumomab pasudotox is a CD22 immunotoxin composed of a binding portion of an anti-CD22 antibody fused to a toxin. After binding to CD22, the molecule is internalised, processed and will release its modified protein toxin that inhibits protein translation, causing tumour cell death.
“This is further evidence of AstraZeneca’s commitment to invest in distinctive science in our core therapy areas and to accelerate our Phase III pipeline,” said Dr. Bahija Jallal, executive vice president of MedImmune, which is AstraZeneca’s global biologics research and development arm. “We believe that targeted therapies, which address the underlying mechanisms of disease, are the future of personalised healthcare to help meet the unmet needs in treating cancer patients. MedImmune’s partnership with the National Cancer Institute is an example of our focus on innovative technologies designed to target cancer cells in more effective ways.”
AstraZeneca also plans to begin Phase III evaluation of olaparib during the second half of 2013 based on Phase II data which demonstrated the agent’s potential as a maintenance treatment for platinum-sensitive relapsed ovarian cancer patients carrying BRCA gene mutations. Olaparib is a potential first-in-class oral poly ADP ribose polymerase (PARP) inhibitor that exploits DNA repair pathway deficiencies to preferentially kill cancer cells.
Results from the Phase II trial will be presented at the American Society of Clinical Oncology (ASCO) Congress in Chicago on 31 May to 4 June. This study evaluated the efficacy of olaparib maintenance therapy compared with placebo in high grade platinum-sensitive relapsed serous ovarian cancer patients. The pre-planned subgroup analysis retrospectively evaluated patients with confirmed gBRCA mutation status and tBRCA mutation status from archival tumour samples.
The company will also present findings from a selumetinib study for the treatment of advanced uveal (eye) melanoma. This randomised trial, sponsored by the National Cancer Institute, compared selumetinib with temozolomide (chemotherapy) in patients with metastatic uveal melanoma. Results from an AstraZeneca-sponsored study will also be presented. This randomised study evaluated selumetinib in combination with dacarbazine as a first-line treatment for advanced cutaneous melanoma patients harboring a mutation of the BRAF gene.
Selumetinib is planned to progress into Phase III evaluation for non small cell lung cancer patients during the second half of this year. The study will investigate selumetinib in combination with docetaxel as a second-line therapy for patients with KRAS mutation-positive and metastatic non small cell lung cancer.
“As one of our three core therapy areas, we are committed to investing in innovative science in oncology to address areas of high unmet medical need,” said Menelas Pangalos, executive vice president of Innovative Medicines and Early Development at AstraZeneca. “The progress we are making with olaparib and selumetinib, combined with our broader early phase portfolio across small molecules and biologics, puts us in a strong position to deliver our pipeline of targeted cancer medicines.”