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:
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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
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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
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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.
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Trial name
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Medicine(s) line of therapy
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Description
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Status
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Immunotherapies
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ATLANTIC
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Durvalumab, third line
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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.
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Ongoing
(recruitment completed for certain cohorts)
Data to be presented in 2016
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ARCTIC
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Durvalumab, third line
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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.
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Currently recruiting
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MYSTIC
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Durvalumab, tremelimumab, first line
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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.
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Currently recruiting
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NEPTUNE
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Durvalumab, tremelimumab,
first line
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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.
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To be initiated
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Name to be announced
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Durvalumab,
first line
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A third first-line Phase III NSCLC trial of durvalumab plus
chemotherapy in PD-L1 unselected, EGFR/ALK wild-type NSCLC.
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To be initiated
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PACIFIC
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Durvalumab,
Stage 3 unresectable
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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.
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Currently recruiting
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AZD9291
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AURA
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AZD9291, first line, second line and beyond
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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.
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Completed recruitment; trial ongoing
Phase I data presented at ESMO 2014, ELCC 2015 and ASCO 2015
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AURA2
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AZD9291, second line and beyond
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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.
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Completed recruitment; trial ongoing
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AURA3
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AZD9291, second line
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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.
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Currently recruiting
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CAURAL
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AZD9291 in combination with durvalumab, second line and beyond
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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.
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Currently recruiting
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FLAURA
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AZD9291, first line
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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.
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Currently recruiting; trial design presented at ASCO 2015
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TATTON
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AZD9291 combinations
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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.
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Currently recruiting; initial trial results presented at ASCO 2015
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Selumetinib
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SELECT1
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Selumetinib, second line
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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)
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Currently recruiting
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-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
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Molecule
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Abstract #, Title and Author
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Time and Location
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AZD9291
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Abstract # 1406
AZD9291 in pre-treated T790M positive advanced NSCLC: AURA2 Phase
II study
Mitsudomi T et al
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16:45 – 18:15, Tuesday, 8 September 2015
Session: MINI 16 – EGFR Mutant Lung Cancer 2
Four Seasons Ballroom F3+F4
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AZD9291
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Abstract # 1232
AZD9291 in treatment-naïve EGFRm advanced NSCLC: AURA first-line
cohort
Ramalingam SS et al
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16:45 – 18:15, Tuesday, 8 September 2015
Session: MINI 16 – EGFR Mutant Lung Cancer 2
Four Seasons Ballroom F3+F4
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AZD9291
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Abstract # 943
AZD9291 in pre-treated T790M positive advanced NSCLC: AURA study
Phase II extension cohort
Yang JC-H et al
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16:45 – 18:15, Tuesday, 8 September 2015
Session: MINI 16 – EGFR Mutant Lung Cancer 2
Four Seasons Ballroom F3+F4
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Gefitinib
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Abstract # 780
Long-Term tolerability among IRESSA Clinical Access Program (ICAP)
participants in the United States (US)
Bunn P et al
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09:30 – 17:00, Monday, 7 September 2015
Session: Poster – P1.01-071
Exhibit Hall (Hall B+C)
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Gefitinib
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Abstract # 3287
Gefitinib/chemotherapy vs chemotherapy in EGFR mutation-positive
NSCLC resistant to first-line gefitinib: IMPRESS T790M subgroup
analysis
Soria JC et al
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10:45 – 12:15, Tuesday, 8 September 2015
Session: ORAL 17.08
Four Seasons Ballroom F3+F4
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Durvalumab (MEDI4736)
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Abstract # 1237
Phase III study of MEDI4736 ± tremelimumab vs standard of care in
advanced NSCLC (ARCTIC )
Planchard D et al
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09:30 – 17:00, Monday, 7 September 2015
Session: Poster – P1.01-082
Exhibit Hall (Hall B+C)
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Durvalumab
(MEDI4736)
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Abstract # 2139
Phase II, study of MEDI4736 in patients with PD-L1+ Stage IIIB–IV
NSCLC (ATLANTIC)
Garassino M et al
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09:30 – 17:00, Monday, 7 September 2015
Session: Poster – P1.01-083
Exhibit Hall (Hall B+C)
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Durvalumab
(MEDI4736)
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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
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09:30 – 17:00, Wednesday, 9 September 2015
Session: Poster – P3.01-090
Exhibit Hall (Hall B+C)
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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 medicines is focused on four main
disease areas - lung, ovarian, breast, and hematological 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 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.
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