Within the rapidly evolving world of cancer treatment and the excitement surrounding immuno-oncology, it is more important than ever to have a strategic approach to ensure new drugs are developed to meet one of the greatest challenges in medicine and tackle one of the leading causes of death.
The figures make for stark reading. According to the most recent World Health Organisation figures1, there were 14 million new cases of cancer in 2012 and that is expected to rise by about 70% over the next two decades.
There have however been major advances in immunotherapies in the last few years, with patients benefiting from durable long-term responses, but there still remains significant unmet need – too few patients are responding to them.
At forefront of innovation
AstraZeneca is well-equipped to address this need, given the breadth of our immuno-oncology pipeline, elements of which will be presented at this year’s European Cancer Congress, which takes place later this month in Vienna. The deep expertise and scientific leadership that characterise our approach has put us at the forefront of innovation when it comes to identifying and filling those areas of unmet need.
It has resulted in the development of our anti-PD-L1 immune checkpoint inhibitor durvalumab (MEDI4736), which is still under investigation.
Combinations are key
Durvalumab may have the potential to combine with both immunotherapy and small molecules so we have continued to follow the scientific evidence to explore novel combination treatments to meet that unmet patient need and considerably increase the number of responders.
Durvalumab is the cornerstone of a comprehensive development programme that is underway across multiple tumour types. Most advanced is the combination with tremelimumab, our anti-CTLA-4 monoclonal antibody, for which three Phase III studies in first-line metastatic non-small cell lung cancer have just been initiated2.
Studies of this combination have shown that while tremelimumab activates an immune response to attack tumours, durvalumab addresses the tumour defense by blocking PD-L1.
In keeping with our commitment to following the science, we are exploring the potential of durvalumab/tremelimumab in areas other than NSCLC. The combination is being investigated in several additional tumour types including head and neck, gastric, pancreatic and bladder cancers3, with the aim of changing the treatment paradigm for patients with a chemotherapy-free regimen.
In addition, we have begun to explore combining our immunotherapy with our DNA-damaging portfolio. By increasing the mutational load, these combinations may work synergistically with immunotherapy. In collaboration with the National Cancer Institute, we have initiated a combination trial to test this hypothesis.
Attracting world-class partners
As well as our own internal R&D efforts, AstraZeneca continues to partner with innovative pharmaceutical companies to maximise the true value of our lead immunotherapy.
A good example of this is a collaboration with Celgene4 which is exploring combinations of durvalumab with the Celgene’s existing and novel haematology compounds across a range of blood cancers including non-Hodgkin’s lymphoma, myelodysplastic syndromes and multiple myeloma. Together with Celgene, a programme has been designed for durvalumab that will explore its full potential as a treatment that could activate the patients’ immune system to fight and change the course of blood cancers.
We are also working with AbbVie’s Pharmacyclics’ unit after preclinical evidence suggested that the combination of durvalumab with the leukaemia and lymphoma therapy ibrutinib has the potential to enhance their effects5.
AstraZeneca is also collaborating with Eli Lilly6 to evaluate durvalumab in combination with ramucirumab, Lilly’s VEGF receptor 2 antiangiogenic as a treatment for patients with advanced solid tumours.
More recently, we began working with Mirati Therapeutics3, combining our anti-PD-L1 inhibitor with mocetinostat, Mirati’s investigational spectrum-selective histone deacetylase inhibitor, initially in NSCLC and possibly additional indications in the future.
In addition to our ties with industry leaders, AstraZeneca has developed strong alliances with key investigator sites to help us access leading-edge oncology research and to rapidly reach the right patients.