Early data for durvalumab monotherapy in NSCLC and HNSCC show durable response rates and encouraging overall survival^1,2

Novel combination data and PD-L1 testing concordance results reinforce commitment to developing treatments for unmet patient needs^3,4

CAMBRIDGE, England -- (BUSINESS WIRE) --

AstraZeneca and its global biologics research and development arm, MedImmune, announced today efficacy and safety data for durvalumab from two separate cohorts of patients with either advanced non-small cell lung cancer (NSCLC) or advanced head and neck squamous cell carcinoma (HNSCC) at the European Society for Medical Oncology (ESMO) 2016 Congress.^1,2 New data from a comparative study of four PD-L1 diagnostic testing assays in HNSCC were also presented at the meeting.³

David Berman, Senior Vice President, Head of Oncology Innovative Medicines at MedImmune, said: “We are presenting encouraging early preliminary data for patients with lung or head and neck cancers at this year’s congress. From efficacy data for durvalumab monotherapy in pre-treated patients to the results of our early-phase trials in combination with novel small-molecule medicines, we have signalled our commitment to finding treatments for patients with these aggressive cancers.”

Positive Preliminary Results for Durvalumab in NSCLC and HNSCC

Follow-up results of the Study 1108 Phase I/II trial of durvalumab as monotherapy in patients with advanced NSCLC showed that patients with high PD-L1-expressing tumours* had higher objective response rate (ORR) and overall survival (OS) compared with patients with low or no PD-L1 expression.¹ ORR (n=287^†) was 25% (95% confidence interval (CI): 19%-33%) in patients with PD-L1-high tumours (n=154) versus 6% (95% CI: 3%-12%) in patients with PD-L1-low tumours (n=116). Estimated six-month OS per line of therapy is indicated in the table below:

^{† Includes 17 patients with unknown PD-L1 tumour expression
*High PD-L1 expression, staining in ≥25% of tumour cells; low PD-L1 expression, staining in <25% of tumour cells}

Among all patients in this cohort, durvalumab demonstrated a safety profile consistent with previous experience.¹ The most frequent treatment-related adverse events (AEs) were fatigue (17%), decreased appetite (9%), and diarrhoea (9%); 5% of patients discontinued treatment due to AEs.¹

In the Study 1108 cohort of patients with metastatic/recurrent HNSCC, ORR was 11% (95% CI: 5%-22%) in all evaluable patients (n=62) and 18% (95% CI: 5%-40%) in patients with PD-L1-high tumours (n=22).² OS was 62% (95% CI: 48%-74%) and 42% (95% CI: 27%-55%) in all evaluable patients at six and 12 months, respectively.² The most common adverse events (AEs) reported in ≥5% of patients were fatigue (18%), diarrhoea and nausea (8% each), pruritus, rash and maculopapular rash (7% each).⁵ Five patients (8%) experienced treatment-related Grade 3-4 AEs.⁵

Novel Molecule Combinations

Early results from the Phase Ib/IIa trial (SCORES) assessing the safety and activity of durvalumab combined with the novel small-molecule STAT3 inhibitor AZD9150 or CXCR2 antagonist AZD5069 in patients with advanced cancers also showed encouraging anti-tumour activity for the two new potential medicines in combination.⁴ Among patients receiving durvalumab plus AZD9150 (n=11), two patients achieved a partial response, and five patients demonstrated stable disease.⁴ Among patients receiving AZD5069 (n=20), one patient demonstrated complete response, two patients demonstrated partial response, and five patients demonstrated stable disease.⁴ Both arms determined the recommended dose for Phase II trials.⁴

The most common AEs were thrombocytopenia (64%), ALT/AST increase (46%), nausea (36%) and neutropenia (36%) among patients receiving AZD9150, and neutropenia (35%), fatigue (25%), and anaemia, anorexia, nausea or pain (all 15%) among patients receiving AZD5069.⁴ One Grade 3 dose-limiting toxicity occurred at the 40 mg/kg dose of AZD5069, and two similar toxicities were noted at 80 mg/kg.⁴

Leadership in PD-L1 Testing

AstraZeneca extended its biomarker concordance testing by assessing the analytical similarities of four commercially available PD-L1 tests.³ The results, which analysed concordance data from 501 commercial HNSCC tumour samples, demonstrated overall percentage agreement of >85% across three of the commercially available tests.³ These results are consistent with previously presented data and advance discussion on the current challenges associated with multiple PD-L1 assays.³

-ENDS-

NOTES TO EDITORS

For more information on AstraZeneca at ESMO, please visit www.twitter.com/AstraZeneca.

About Durvalumab

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1) and is designed to help activate the immune system against tumours.⁶ Durvalumab blocks PD-L1 interaction with PD-1 and the costimulatory ligand CD80 on T cells, which maximizes T-cell activation. By inhibiting PD-L1, durvalumab helps increase T-cell activity against the tumour to counter its efforts to evade the immune system.^6,7 AstraZeneca is developing durvalumab as the primary molecule in a combination-focused approach to empowering the immune system against cancer.⁸ In 2015, durvalumab received Fast Track Designation for the treatment of patients with PD-L1-positive metastatic HNSCC,⁹ and in 2016, durvalumab was granted Breakthrough Therapy Designation by the US Food and Drug Administration for the treatment of patients with PD-L1-positive inoperable or metastatic urothelial bladder cancer whose tumour has progressed during or after one standard platinum-based regimen.¹⁰

AstraZeneca’s Approach to Immuno-Oncology (IO)

Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to destroy tumours.^11,12,13 At AstraZeneca, and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression.^7,14 We believe that IO-based therapies will offer the potential for life-changing anti-cancer treatments for the vast majority of patients.

We are pursuing a comprehensive clinical trial programme that includes durvalumab (PD-L1) monotherapy and durvalumab in combination with tremelimumab (CTLA-4) in multiple tumour types, stages of disease, and lines of therapy,⁶ using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small targeted molecules from across our oncology pipeline, and with those of our partners, may provide new treatment options across a broad range of tumours.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms -- Immuno-Oncology, the genetic drivers of cancer and resistance, DNA damage response and antibody drug conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About MedImmune

MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including oncology; respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; and infection and vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centres, with additional sites in Cambridge, UK and Mountain View, CA. For more information, please visit www.medimmune.com.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Respiratory & Autoimmunity, Cardiovascular & Metabolic Diseases, and Oncology. The Company is also active in inflammation, infection and neuroscience through numerous collaborations. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com

Intended audiences

This press release is issued from AstraZeneca Corporate Headquarters in Cambridge, UK and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where AstraZeneca conducts business.

References

¹ Antonia S et al. Phase 1/2 study of the safety and clinical activity of durvalumab in patients with non-small cell lung cancer (NSCLC). European Society for Medical Oncology 2016 Congress (Poster). To be presented October 2016.

² Segal NH et al. Updated safety and efficacy of durvalumab (MEDI4736), an anti-PD-L1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) expansion cohort. European Society for Medical Oncology 2016 Congress. To be presented October 2016.

³ Ratcliffe MJ et al. A comparative study of PD-L1 diagnostic assays in squamous cell carcinoma of the head and neck (SCCHN). European Society for Medical Oncology 2016 Congress (Poster abstract). To be presented October 2016.

⁴ Hong D et al. A Phase 1b Study (SCORES) Assessing Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of Durvalumab Combined with AZD9150 or AZD5069 in Patients with Advanced Solid Malignancies and SCCHN. European Society for Medical Oncology 2016 Congress (Poster abstract). To be presented October 2016.

⁵ AstraZeneca. Data on File. October 2016.

⁶ Stewart R et al. Identification and Characterization of MEDI4736, an Antagonistic Anti–PD-L1 Monoclonal Antibody. Cancer Immunol Res; 2015. Published OnlineFirst May 5, 2015; doi: 10.1158/2326-6066

⁷ Patel SP and R Kurzrock. PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Mol Cancer Ther 2015; 14:847-856. Published OnlineFirst February 18, 2015.

⁸ AstraZeneca. H1 2016 Results. 28 July 2016. Available at https://www.astrazeneca.com/content/dam/az/press-releases/2016/H1_2016_Results_announcement.pdf. Accessed September 2016.

⁹ AstraZeneca. AstraZeneca reports top-line result of tremelimumab monotherapy trial in mesothelioma. 29 February 2016. Available at https://www.astrazeneca.com/media-centre/press-releases/2016/astrazeneca-reports-top-line-result-of-tremelimumab-monotherapy-trial-in-mesothelioma-29022016.html. Accessed September 2016.

¹⁰ AstraZeneca. Durvalumab granted Breakthrough Therapy Designation by US FDA for treatment of patients with PD-L1 positive urothelial bladder cancer. 17 February 2016. Available at https://www.astrazeneca.com/media-centre/press-releases/2016/Durvalumab-granted-Breakthrough-Therapy-designation-by-US-FDA-for-treatment-of-patients-with-PD-L1-positive-urothelial-bladder-cancer-17022016.html. Accessed September 2016.

¹¹ Eggermont E & Finn O. Advances in immuno-oncology. Annals of Oncology 23 (Supplement 8): viii5, 2012. doi: 10.1093/annonc/mds255

¹² Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Annals of Oncology 23(Supplement 8): viii6-viii9, 2012. doi: 10.1093/annonc/mds256

¹³ Melero I et al. Clinical Development of Immunostimulatory Monoclonal Antibodies and Opportunities for Combination. Clin Cancer Res 2013;19:997-1008.

¹⁴ Bograd AJ et al. Immune responses and immunotherapeutic interventions in malignant pleural mesothelioma. Cancer Immunol Immunother. 2011 Nov;60(11):1509-27.

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