AstraZeneca to Update on Progress with Immuno-Oncology Pipeline and Combination Treatments at ASCO 2015

AstraZeneca and MedImmune, the Company’s global biologics research and development arm, will demonstrate rapid progress with their combination-focused oncology pipeline at the American Society of Clinical Oncology (ASCO) Annual Meeting, May 29-June 2, 2015. 61 scientific abstracts2 will be presented at the meeting, reinforcing the significant progress in immuno-oncology through combination therapies and innovative companion diagnostics.

Briggs Morrison, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “We are pleased to update on the breadth and depth of our oncology pipeline at ASCO. Our small molecule and biologic treatments target multiple areas of tumour biology across a diverse range of cancers, alone or in combination. It is especially encouraging to see the potential impact of our work in non-small cell lung cancer at different stages of the disease pathway and for different types of patients.”

“In immuno-oncology, we are starting to see the transformational potential of combination therapies, which are at the heart of our vision of redefining cancer treatment. The maturing data reinforce our confidence in this strategy, and, in particular, in MEDI4736, which is showing durable activity across multiple tumour types and in different combinations. This progress offers the possibility of helping patients who don’t respond to standard of care or current monotherapies.”

Bahija Jallal, Executive Vice President, MedImmune, said: “Our understanding of the potential of immuno-oncology is fast evolving as we begin to unlock its benefits for a greater number of patients – however we have only scratched the surface so far. Our comprehensive, combination-focused development program aims to rapidly deepen our scientific understanding, exploring all the critical areas of the immune system that cancer can hijack to escape destruction. Through the use of companion diagnostics, we can also fully understand the clinical value of our investigational immunotherapies, both as monotherapy and in combination, for different types of patients and across many different types of cancer.”

Highlights at the ASCO Annual Meeting will include data from across the Company’s broad pipeline of next-generation investigational medicines, which target cancer through key areas of tumor biology including immunotherapy, the genetic drivers of cancer and acquired resistance and DNA damage repair.

Immuno-oncology

Immunotherapies use the body's own immune system to help fight cancer. There are three major components to an effective cancer immune response: priming and activation of T-cells (white blood cells that play a central role in immune response) through cancer antigen presentation; optimizing T-cell mediated cancer cell killing by overcoming inhibitory mechanisms employed by the cancer; and overcoming immune suppressive mechanisms in the tumor microenvironment to further enhance an effective anti-tumor immune response.

At the ASCO Annual Meeting AstraZeneca will provide an update on its comprehensive immuno-oncology development program, which includes 31 ongoing clinical trials targeted across this cycle of anti-tumor immunity. Data to be presented at ASCO are supported by a number of recent milestones including:

• Start of the combination arm of the Phase III ARCTIC study of MEDI4736 with tremelimumab in non-small cell lung cancer (NSCLC) patients who have received at least two prior systemic treatment regimens.
• Start of the Phase II CONDOR study of MEDI4736 and tremelimumab as monotherapies and in combination in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN).
• Fast-Track designation granted by the FDA for the investigation of MEDI4736 as a monotherapy treatment for patients with advanced NSCLC, who have received at least two prior systemic-treatment regimens, who do not have EGFR mutations or anaplastic lymphoma kinase (ALK) alterations, and have tumors that are determined to be PD-L1 positive.
• In addition to testing the potential of immunotherapies in solid tumors, AstraZeneca recently entered into a strategic collaboration with Celgene, a global leader in haematological cancers, on a broad development program for MEDI4736, both as monotherapy and in combination with other molecules, across a range of blood cancers including multiple myeloma, non-Hodgkin’s lymphoma and myelodysplastic syndrome.

Presentations to include:

• Safety and efficacy of MEDI4736 in combination with tremelimumabin patients with NSCLC [Abstract #3014]. Updated data on additional patients and activity in both PD-L1 positive and negative patients to be presented.
• Safety and efficacy of the triple combination of MEDI4736 with BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in patients with advanced melanoma [Oral Abstract #3003].
• An open-label study of MEDI4736 in combination with MEDI0680 (anti-PD-1) in patients with advanced malignancies [Trials in Progress Poster #TPS3087].
• Updates reinforcing the clinical activity of MEDI4736 as monotherapy in patients with NSCLC [Abstract #8032], in patients with recurrent or metastatic SCCHN [Abstract #3011], and on the development of a PD-L1 companion diagnostic assay [Abstract #8033].

Genetic drivers of cancer and resistance

AstraZeneca has a strong legacy in research into the genetic drivers of cancer and resistance. Iressa (gefitinib), originally approved in Japan in 2002 and currently under review with the US Food and Drug Administration (FDA). Data to be presented at ASCO will focus on AZD9291, an investigational, highly selective, irreversible inhibitor of both the activating sensitizing EGFR mutation (EGFRm) and the activating resistance mutation, T790M.

Patients with EGFRm NSCLC are particularly sensitive to treatment with currently available EGFR tyrosine kinase inhibitors (TKIs), which block the cell signalling pathways that drive the growth of tumor cells. However, tumor cells almost always develop resistance to treatment, leading to disease progression. In approximately two thirds of patients, this resistance is caused by the secondary mutation, T790M. No currently targeted therapies are approved for the treatment of tumors with this resistance mutation.

AZD9291 presentations at ASCO to include:

• Early efficacy and safety data from the multi-arm Phase Ib TATTON study, testing AZD9291 in combination with one of three treatments in patients with advanced, EGFR-mutant NSCLC who have progressed on prior EGFR TKI therapy [Abstract #2509]. The treatments are MEDI4736; savolitinib (AZD6094), an investigational, highly potent and selective c-MET inhibitor; or selumetinib, a potent, selective inhibitor of MEK1/2 kinases.

• Detail on the Phase III FLAURA clinical trial testing AZD9291 versus standard doses of gefitinib or erlotinib in treatment-naïve patients with EGFR-mutant advanced NSCLC [Trials in Progress Poster #TPS8102].
• Data from the Phase I AURA study testing AZD9291 as first-line therapy for patients with NSCLC, compared against currently approved EGFR medicines [Abstract #8000].

Data presented at ASCO build on the updated progression-free survival (PFS) data for AZD9291 as second line therapy for patients with EGFR-mutated NSCLC, who also have the T790M resistance mutation, which was presented at the recent European Lung Cancer Conference. The data demonstrated a median PFS of 13.5 months (95% confidence interval (CI) 8.3 months to not calculable (NC)). These PFS findings relate to independently reviewed data from 63 patients with T790M tumors treated with AZD9291 at a dose of 80mg per day, and are based on only 38% of patients having tumor progression. In patients treated with AZD9291 80mg, the most common all-cause adverse events (AEs) of any grade were rash, 38% (0% Grade ≥3) and diarrhea, 36% (1% Grade ≥3). Investigator-determined treatment-related Grade ≥3 AEs occurred in 14% of patients.

DNA Damage Repair

AstraZeneca has the largest portfolio of potential medicines targeted at DNA damage repair, including the recently launched LYNPARZA™ (olaparib) capsules, an oral poly ADP-ribose polymerase (PARP) inhibitor, indicated as a monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Serious adverse reactions have occurred with LYNPARZA, and the most common adverse reactions were anemia, fatigue, and gastrointestinal disorders. Please see Important Safety Information later in this release.

During ASCO, new data will be presented on olaparib and on AZD1775, a small molecule designed to inhibit the tyrosine kinase called Wee1, which helps to regulate the cell-division cycle, and is undergoing testing for the treatment of ovarian cancer. AZD1775 is designed to cause certain tumor cells to divide without undergoing the normal DNA repair processes, ultimately leading to cell death. Preclinical evidence suggests that the combination of AZD1775 and DNA damage-inducing chemotherapy agents can enhance anti-tumor properties, in comparison to chemotherapy alone.

• Data on the genomic characterization of long-term responders to Lynparza will provide further insight into the physiology of ovarian cancer patients seeing benefit from the medicine [Abstract #5566].
• Data from an international biomarker-directed randomized Phase II trial of AZD1775 used in combination with paclitaxel and carboplatin for the treatment of women with platinum-sensitive, TP53 mutated ovarian cancer [Oral Abstract #5506].
• Data from a Phase II study of AZD1775 plus carboplatin in patients with TP53 mutated ovarian cancer refractory or resistant (three or fewer months) to standard first line therapy [Oral Abstract #2507].

NOTES TO EDITORS

1 Novartis medicines for treatment of patients with metastatic melanoma.
2 Data included in abstracts are preliminary only and do not represent full data sets.

About LYNPARZA

LYNPARZA is a first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor. The FDA’s approval follows the announcement on December 18 of the approval of LYNPARZA in the European Union.

AstraZeneca is conducting multiple Phase III studies across a variety of indications and tumor types for LYNPARZA. For more information visit www.astrazenecaclinicaltrials.com.

LYNPARZA is a trademark of the AstraZeneca group of companies.

Important Safety Information

There are no contraindications for LYNPARZA.

LYNPARZA may cause serious side effects that can lead to death including bone marrow problems and lung problems. Some people who have ovarian cancer or who have received previous treatment with chemotherapy or certain other medicines for their cancer have developed bone marrow problems called Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) during treatment with LYNPARZA. If you develop MDS or AML, your healthcare provider will stop treatment with LYNPARZA.

Symptoms of low blood cell counts are common during treatment with LYNPARZA, but can be a sign of serious bone marrow problems, including MDS or AML. Symptoms to discuss with your healthcare provider include weakness, weight loss, fever, frequent infections, blood in your urine/stool, shortness of breath, feeling very tired, and bruising or bleeding more easily.

You will undergo blood tests before, and every month during, treatment with LYNPARZA to monitor your blood cell counts. Weekly blood tests will be performed if you have low blood cell counts that last a long time. Your healthcare provider may stop treatment with LYNPARZA until your blood cell counts improve.

Tell your healthcare provider if you have any new or worsening symptoms of lung problems, including shortness of breath, fever, cough, or wheezing. Your healthcare provider may do a chest x-ray if you have any of these symptoms. Your healthcare provider may temporarily or completely stop treatment if you develop pneumonitis.

Before you take LYNPARZA, tell your healthcare provider if you:

• Have lung or breathing problems
• Have liver problems
• have kidney problems
• Are pregnant or plan to become pregnant. LYNPARZA can harm your unborn baby and may cause loss of pregnancy (miscarriage). You should not become pregnant during treatment with LYNPARZA. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
  • Females who are able to become pregnant should use effective birth control (contraception) during treatment with LYNPARZA and for at least 1 month after receiving the last dose of LYNPARZA.
  • Talk to your healthcare provider about birth control methods that may be right for you.
  • Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LYNPARZA.
• Are breastfeeding or plan to breastfeed. It is not known if LYNPARZA passes into your breast milk. You and your healthcare provider should decide if you will take LYNPARZA or breastfeed. You should not do both.

Avoid grapefruit, grapefruit juice and Seville oranges during treatment as they may increase the levels of LYNPARZA in your blood.

The most common side effects are anemia, nausea or vomiting, tiredness or weakness, diarrhea, indigestion or heartburn, headache, loss of appetite, changes in how food tastes, changes in kidney function blood tests, sore throat or runny nose, upper respiratory infection, cough, pain in the joints, muscles, and back, rash, and pain or discomfort in the stomach area.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of LYNPARZA. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For complete product information, including patient information (Medication Guide), visit www.lynparza.com or call 1-800-263-9933.

About AstraZeneca in Oncology

Oncology is a therapeutic area in which AstraZeneca has deep-rooted heritage. It will be potentially transformational for the Company’s future, becoming the sixth growth platform. Our vision is to help patients by redefining the cancer treatment paradigm and one-day eliminate cancer as cause of death. By 2020, we are aiming to bring six new cancer medicines to patients.

Our broad pipeline of next-generation investigational medicines is focused on four main disease areas - ovarian, lung, breast, and haematological cancers. These are being targeted through four key platforms – immuno-oncology, the genetic drivers of cancer and resistance, DNA damage repair and antibody drug conjugates.

About MedImmune

MedImmune is the worldwide biologics research and development arm of AstraZeneca. MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; oncology; neuroscience; and infection and vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centres. For more information, please visit www.medimmune.com.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit www.astrazeneca-us.com.