Imfinzi is the only immunotherapy to demonstrate overall survival at three years in unresectable Stage III non-small cell lung cancer

Data presented at ASCO 2019 showed 57% of patients
alive at three years vs. 43.5% on placebo

AstraZeneca has presented three-year overall survival (OS) results from the Phase III PACIFIC trial of Imfinzi (durvalumab) in unresectable, Stage III non-small cell lung cancer (NSCLC) during the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

These latest results show a durable and sustained OS benefit in patients with unresectable, Stage III NSCLC who had not progressed following concurrent chemoradiation therapy (CRT), a previous standard-of-care (SoC) treatment. The OS rate was 57% at three years for patients receiving Imfinzi vs. 43.5% for placebo following concurrent CRT. Median OS was not yet reached with the Imfinzi arm vs. 29.1 months for placebo.

Dave Fredrickson, Executive Vice President, Oncology Business Unit said: “These findings for Imfinzi are another example of our focus on bringing long-term survival benefits to patients who still have a chance of being cured. These three-year survival results further establish the PACIFIC regimen as the standard of care for these patients, and we are optimistic this survival trend will continue as we move towards the five-year landmark in this curative-intent setting.”

Results build on the primary two-year OS analysis that was published in The New England Journal of Medicine in September 2018 and demonstrated a significant OS benefit for treatment with Imfinzi vs. placebo after CRT, regardless of PD-L1 expression. The primary analysis showed Imfinzi reduced the risk of death by 32% (HR 0.68, [99.73% CI, 0.47-0.997], p=0.0025).

With the additional year of follow up, the latest results for Imfinzi showed consistent and durable efficacy, maintaining a 31% reduction in the risk of death vs. placebo after CRT (HR 0.69, [95% CI 0.55-0.86]).

Jhanelle Gray, MD, Director of Clinical Research in the Thoracic Oncology Department at Moffitt Cancer Center in Tampa, Florida, and an investigator in the PACIFIC trial, said: “In the past, patients with unresectable, Stage III non-small cell lung cancer faced five-year survival rates of only 15% to 30%. It is remarkable to see that more than half of patients treated with the PACIFIC regimen remain alive at three years, an important milestone that raises the bar for treatments in this curative-intent setting.”

The safety and tolerability profile for Imfinzi was consistent with the results reported at the time of the previous OS analysis. Among patients receiving Imfinzi, the most common adverse events (AE) (greater than or equal to 20% of patients) vs. placebo were cough (35.2% vs. 25.2%), fatigue (24.0% vs. 20.5%), dyspnoea (22.3% vs. 23.9%) and radiation pneumonitis (20.2% vs. 15.8%). 30.5% of patients experienced a grade 3 or 4 AE with Imfinzi vs. 26.1% with placebo, and 15.4% of patients discontinued treatment due to AEs with Imfinzi vs. 9.8% of patients on placebo.

Building on PACIFIC

AstraZeneca has several ongoing trials focused on testing Imfinzi in earlier stages of NSCLC (Stages I-III) in potentially-curative settings. The Phase III PACIFIC-2 trial design, presented today at the ASCO Annual Meeting, is evaluating Imfinzi given concurrently with CRT in patients with unresectable, Stage III NSCLC. In the Phase II PACIFIC-6 trial, Imfinzi is being tested in the same population following sequential chemotherapy and radiation therapy.

Additional trials assess Imfinzi in the neoadjuvant setting (prior to other treatments) in Stage II and III NSCLC patients (AEGEAN) and in the adjuvant setting (following the primary treatment) in Stage I to III (BR.31). The Phase III PACIFIC-4 trial is testing Imfinzi in unresected Stage I and II NSCLC patients following definitive stereotactic body radiation therapy (SBRT).

AstraZeneca is also testing novel combinations with Imfinzi in two Phase II platform trials in both unresectable, Stage III disease (COAST) and in resectable Stage I-III disease starting before surgery (NeoCOAST), to help find solutions for NSCLC patients not benefiting from currently-available therapies.

<sup>1. EGFR = epidermal growth factor receptor, ALK = anaplastic lymphoma kinase
2. BR.31 is an externally-sponsored research study led by the Canadian Cancer Trials Group (CCTG)</sup> 

Imfinzi is approved for the treatment of unresectable, Stage III non-small cell lung cancer in more than 45 countries, including the US, EU and Japan, based on the Phase III PACIFIC trial. Since the first approval in February 2018, more than 20,000 patients in this setting have been treated with Imfinzi.

About PACIFIC

The PACIFIC trial is a Phase III, randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in ‘all-comer’ patients (i.e. regardless of PD-L1 status) with unresectable, Stage III (locally-advanced) NSCLC whose disease has not progressed following platinum-based chemotherapy and radiation therapy (CRT).

The trial is being conducted in 235 centres across 26 countries involving 713 patients. The primary endpoints of the trial are progression-free survival (PFS) and OS, and secondary endpoints include landmark PFS and OS, objective response rate, and duration of response.

About Stage III NSCLC

Stage III (locally-advanced) NSCLC is commonly divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery.¹ Stage III disease is different from Stage IV disease, when the cancer has spread (metastasised) to distant organs, as Stage III is currently treated with curative intent.^1,2

Stage III NSCLC represents approximately one-third of NSCLC incidence and was estimated to affect nearly 200,000 patients in the top-eight countries (China, France, Germany, Italy, Japan, Spain, UK, US) in 2015.^3,4 The majority of Stage III NSCLC patients are diagnosed with unresectable tumours.⁵ No new treatments beyond chemoradiation therapy, followed by active surveillance to monitor for progression, have been available to patients for decades.^6-9

About Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved for unresectable, Stage III NSCLC in more than 45 countries including the US, in the EU, and Japan based on the Phase III PACIFIC trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small cell lung cancer, bladder cancer, head and neck cancer, liver cancer, cervical cancer, biliary tract cancer and other solid tumours.

About AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of different forms of lung cancer spanning several stages of disease, lines of therapy and modes of action. We aim to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa (gefitinib) and Tagrisso (osimertinib), and ongoing Phase III trials FLAURA, ADAURA and LAURA as well as the Phase II exploratory combination trials SAVANNAH and ORCHARD.^10-12

Our extensive late-stage Immuno-Oncology programme focuses on lung cancer patients without a known genetic mutation which represents up to 50% of all patients with lung cancer. Imfinzi (durvalumab), an anti-PDL1 antibody, is in development as monotherapy (Phase III trials ADJUVANT BR.31, PACIFIC-4, PACIFIC-5, and PEARL) and in combination with tremelimumab and/or chemotherapy (AEGEAN, PACIFIC-2, NEPTUNE, POSEIDON, ADRIATIC and CASPIAN Phase III trials).

About AstraZeneca’s approach to Immuno-Oncology (IO)

IO is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. Our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies offer the potential for life-changing cancer treatments for the clear majority of patients.

We are pursuing a comprehensive clinical-trial programme that includes Imfinzi (anti-PDL1) as monotherapy and in combination with tremelimumab (anti-CTLA4) in multiple tumour types, stages of disease, and lines of therapy, 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 from our research 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 Oncology as a key growth driver for AstraZeneca 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, Tumour Drivers 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 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 - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit astrazeneca.com and follow us on Twitter @AstraZeneca.

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References

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^{9 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Non-small cell lung cancer, version 8. 2017. https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf. Published August 3, 2017. Accessed May 2019.}

^{10 Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12. Accessed May 2019.}

^{11 Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27. Accessed May 2019.}

^{12 Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89. Accessed May 2019.}