AstraZeneca to Update on Leading Lung Cancer Portfolio at WCLC 2015

Data will be reported from across AstraZeneca's industry-leading lung cancer portfolio at the World Conference on Lung Cancer (WCLC) 2015, beginning this weekend in Denver, Colorado. Presentations will feature 25 abstracts (including 9 oral and 4 late breaker presentations) on the company's lung cancer pipeline, designed to address the unmet needs of patients with different forms of lung cancer. AZD9291 (osimertinib)1: Targeting resistance mechanisms in lung cancer AZD9291 will be the focus of six oral presentations on its clinical activity in both first-line and previously-treated patients with epidermal growth factor receptor mutation (EGFRm) T790M advanced non-small cell lung cancer (NSCLC). The data are consistent with previously reported efficacy and safety results of AZD9291 in these treatment settings. Antoine Yver, Head of Oncology, Global Medicines Development at AstraZeneca said: "The data presented at WCLC illustrate the breadth of our lung cancer research across multiple disease settings and lines of therapy, as we aim to develop a comprehensive portfolio of effective and durable treatments for patients. AZD9291 is moving through clinical development with unprecedented speed, and was recently granted US Priority Review designation in recognition of its potential to target the mutation that drives resistance to current treatments for EGFR mutation positive advanced non-small cell lung cancer in the majority of patients." In addition to AZD9291, AstraZeneca will also present results from the IRESSA® (gefitinib) Clinical Access Program (ICAP), which provides data on the long-term safety and tolerability of the EGFR tyrosine kinase inhibitor in 188 US cancer patients outside the clinical trial setting. IRESSA® was approved by the US Food and Drug Administration (FDA) in July 2015, and is already available in 91 countries worldwide. Immuno-oncology (IO): Update on key clinical trials Trial designs for the ongoing IO late-stage studies that will be presented at WCLC include: ATLANTIC (NCT02087423): A Phase II trial of durvalumab (PD-L1 mAb) as third-line treatment in patients with PD-L1 positive, locally advanced or metastatic NSCLC ARCTIC (NCT 02352948): A Phase III trial of durvalumab monotherapy and in combination with tremelimumab (CTLA-4 mAb) versus standard of care in third-line metastatic NSCLC PACIFIC (NCT02125461): A Phase III placebo-controlled trial of durvalumab compared to placebo in patients with locally advanced, unresectable, NSCLC following completion of treatment with chemoradiotherapy and no evidence of tumor progression. Robert Iannone, Head of Immuno-Oncology, Global Medicines Development, at AstraZeneca said: "WCLC provides another opportunity for us to update the medical community on our extensive immuno-oncology development program in lung cancer. We have made tremendous progress in developing immuno-oncology-based combination approaches, with nine pivotal studies planned or underway in NSCLC alone, which will provide us with a steady stream of research milestones in the coming months." The FDA has granted Fast Track designation to tremelimumab for the treatment of mesothelioma, an aggressive, rare form of cancer that affects the lining of the lungs and abdomen. Durvalumab was also granted Fast Track designation 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. AstraZeneca Pivotal Studies in Lung Cancer Data presented at WCLC are part of AstraZeneca's rapidly advancing lung cancer program, which includes the following pivotal clinical trials and upcoming milestones. Trial name Medicine(s) line of therapy Description Status Immunotherapies ATLANTIC Durvalumab, third line A Phase II trial in third-line metastatic NSCLC assesses the efficacy of durvalumab in tumors that are PD-L1 positive in patients with locally advanced or metastatic NSCLC who have received two or more prior systemic treatments. Ongoing (recruitment completed for certain cohorts) Data to be presented in 2016 ARCTIC Durvalumab, third line The Phase III trial in third-line metastatic NSCLC is recruiting patients and contains a randomized durvalumab monotherapy sub-study for PD-L1 positive tumors versus standard of care (SoC) and a sub-study with a concurrent-combination treatment with tremelimumab versus the contribution of components and SoC in patients with PD-L1 negative tumors. Currently recruiting MYSTIC Durvalumab, tremelimumab, first line A Phase III durvalumab-tremelimumab trial in first-line metastatic NSCLC, which is recruiting in PD-L1 unselected, EGFR/ALK wild-type patients and includes a sub-group analysis of PD-L1 positive and PD-L1 low/negative tumors. The primary endpoint is progression free survival PFS and the trial includes durvalumab monotherapy and the durvalumab-tremelimumab combination versus SoC. Currently recruiting NEPTUNE Durvalumab, tremelimumab, first line A further Phase III durvalumab-tremelimumab study in the first-line metastatic NSCLC setting, versus SoC with overall survival (OS) as the primary endpoint; complements the MYSTIC PFS trial. To be initiated Name to be announced Durvalumab, first line A third first-line Phase III NSCLC trial of durvalumab plus chemotherapy in PD-L1 unselected, EGFR/ALK wild-type NSCLC. To be initiated PACIFIC Durvalumab, Stage 3 unresectable A Phase III trial assessing the PFS and OS with durvalumab compared to placebo in patients with locally advanced, unresectable, NSCLC following completion of treatment with chemoradiotherapy and no evidence of tumor progression. Currently recruiting AZD9291 AURA AZD9291, first line, second line and beyond Phase I/II open label, dose escalation and expansion cohort study to investigate the safety and tolerability, pharmacokinetics and response to therapy of AZD9291 in patients with advanced NSCLC who had disease progression following treatment with an approved EGFR TKI. Completed recruitment; trial ongoing Phase I data presented at ESMO 2014, ELCC 2015 and ASCO 2015 AURA2 AZD9291, second line and beyond Phase II, open-label, single-arm confirmatory trial to assess the safety and efficacy of AZD9291 in patients with advanced or metastatic NSCLC whose disease has progressed with previous EGFR-TKI therapy and whose tumors harbor an EGFR and T790M mutation. Completed recruitment; trial ongoing AURA3 AZD9291, second line Phase III, open label, randomized study of AZD9291 versus platinum-based doublet chemotherapy for patients with locally advanced or metastatic NSCLC whose disease has progressed with previous TKI therapy and with the EGFR and T790M mutation. Currently recruiting CAURAL AZD9291 in combination with durvalumab, second line and beyond A Phase III, open label, randomized trial to assess the efficacy and safety of AZD9291 in combination with durvalumab versus AZD9291 monotherapy in patients with locally advanced or metastatic EGFR receptor T790M mutation-positive NSCLC who have received prior EGFR TKI therapy. Currently recruiting FLAURA AZD9291, first line A Phase III, double blind, randomized trial comparing the efficacy and safety of AZD9291 versus SoC EGFR-TKI treatment (gefitinib or erlotinib) in treatment-naïve patients with locally advanced or metastatic EGFRm NSCLC. Currently recruiting; trial design presented at ASCO 2015 TATTON AZD9291 combinations A multi-arm, Phase Ib trial investigating AZD9291 in combination with durvalumab, savolitinib (MET inhibitor; AZD6094) or selumetinib (MEK1/2 inhibitor; AZD6244, ARRY-142886) in patients with advanced EGFR mutant lung cancer that has progressed on previous EGFR TKI treatment. Currently recruiting; initial trial results presented at ASCO 2015 Selumetinib SELECT1 Selumetinib, second line A phase III, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of selumetinib in combination with docetaxel, in patients receiving second-line treatment for KRAS mutation-positive locally advanced or metastatic NSCLC (Stage IIIB - IV) Currently recruiting -ENDS- NOTES TO EDITORS 1 Osimertinib has recently been published by the World Health Organization (WHO) as the proposed International Nonproprietary Name (INN) for AZD9291, and may become formally adopted by November 2015. Key data presentations at WCLC 2015 Molecule Abstract #, Title and Author Time and Location AZD9291 Abstract # 1406 AZD9291 in pre-treated T790M positive advanced NSCLC: AURA2 Phase II study Mitsudomi T et al 16:45 – 18:15, Tuesday, 8 September 2015 Session: MINI 16 – EGFR Mutant Lung Cancer 2 Four Seasons Ballroom F3+F4 AZD9291 Abstract # 1232 AZD9291 in treatment-naïve EGFRm advanced NSCLC: AURA first-line cohort Ramalingam SS et al 16:45 – 18:15, Tuesday, 8 September 2015 Session: MINI 16 – EGFR Mutant Lung Cancer 2 Four Seasons Ballroom F3+F4 AZD9291 Abstract # 943 AZD9291 in pre-treated T790M positive advanced NSCLC: AURA study Phase II extension cohort Yang JC-H et al 16:45 – 18:15, Tuesday, 8 September 2015 Session: MINI 16 – EGFR Mutant Lung Cancer 2 Four Seasons Ballroom F3+F4 Gefitinib Abstract # 780 Long-Term tolerability among IRESSA Clinical Access Program (ICAP) participants in the United States (US) Bunn P et al 09:30 – 17:00, Monday, 7 September 2015 Session: Poster – P1.01-071 Exhibit Hall (Hall B+C) Gefitinib Abstract # 3287 Gefitinib/chemotherapy vs chemotherapy in EGFR mutation-positive NSCLC resistant to first-line gefitinib: IMPRESS T790M subgroup analysis Soria JC et al 10:45 – 12:15, Tuesday, 8 September 2015 Session: ORAL 17.08 Four Seasons Ballroom F3+F4 Durvalumab (MEDI4736) Abstract # 1237 Phase III study of MEDI4736 ± tremelimumab vs standard of care in advanced NSCLC (ARCTIC ) Planchard D et al 09:30 – 17:00, Monday, 7 September 2015 Session: Poster – P1.01-082 Exhibit Hall (Hall B+C) Durvalumab (MEDI4736) Abstract # 2139 Phase II, study of MEDI4736 in patients with PD-L1+ Stage IIIB–IV NSCLC (ATLANTIC) Garassino M et al 09:30 – 17:00, Monday, 7 September 2015 Session: Poster – P1.01-083 Exhibit Hall (Hall B+C) Durvalumab (MEDI4736) Abstract # 1263 Phase III, double-blind, placebo-controlled study of MEDI4736 after chemoradiation in Stage III, locally advanced, unresectable NSCLC (PACIFIC) Kim J-H et al 09:30 – 17:00, Wednesday, 9 September 2015 Session: Poster – P3.01-090 Exhibit Hall (Hall B+C)