a3956o2
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of May
2020
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Imfinzi showed
a sustained overall survival benefit in 1st-line
extensive-stage small cell lung cancer in the Phase III CASPIAN
trial
29 May 2020 13:00 BST
Imfinzi showed
a sustained overall survival benefit in
1st-line
extensive-stage small cell lung cancer in the Phase III CASPIAN
trial
ASCO data show more than 10% of patients on Imfinzi plus
chemotherapy had not progressed and remained on treatment at two
years vs. 2.9% on chemotherapy alone
Detailed results from an updated analysis of the Phase III CASPIAN
trial showed AstraZeneca's Imfinzi (durvalumab) in combination with a choice of
chemotherapies, etoposide plus either carboplatin or cisplatin,
demonstrated a sustained, clinically meaningful overall survival
(OS) benefit for adults with extensive-stage small cell lung cancer
(ES-SCLC) treated in the 1st-line setting.
The CASPIAN trial met the primary endpoint of OS
in June
2019, reducing the risk of
death by 27% (based on a hazard ratio [HR] of 0.73; 95% confidence
interval [CI] 0.59-0.91; p=0.0047) which formed the basis of the US
FDA approval in March
2020.
After a median follow up of more than two years, the latest results
for Imfinzi plus chemotherapy showed sustained efficacy,
maintaining a 25% reduction in the risk of death versus
chemotherapy alone (based on an HR of 0.75; 95% CI 0.62, 0.91;
nominal p=0.0032). Updated median OS was 12.9 months versus 10.5
for chemotherapy. In a post-hoc analysis, an estimated 22.2% of
patients treated with Imfinzi plus chemotherapy were alive at 24 months
versus 14.4% for chemotherapy.
For Imfinzi plus chemotherapy, 11% of patients were
alive and progression-free at 24 months versus 2.9% for
chemotherapy alone (post-hoc). Imfinzi plus chemotherapy maintained a high
confirmed objective response rate (ORR) (68% versus 58%) and in a
post-hoc analysis, duration of response (DoR)
for Imfinzi at 24 months was 13.5% versus 3.9% for
chemotherapy. At 24 months, 12% of patients in
the Imfinzi plus chemotherapy arm remained
on Imfinzi treatment.
Luis Paz-Ares MD, Ph.D., Chair, Medical Oncology Department,
Hospital Universitario Doce de Octubre, Madrid, Spain and principal
investigator in the Phase III CASPIAN trial said: "These updated
results from the CASPIAN trial show a remarkable 22% of patients
still alive at 24 months, supporting the sustained benefits of
treatment with Imfinzi plus chemotherapy. This is an effective
1st-line treatment in the extensive-stage setting, where improving
outcomes has been a challenge and so few patients survive five
years."
José Baselga, Executive Vice President, Oncology R&D,
said: "After two years median follow-up, Imfinzi continues to show sustained and meaningful
improvements in survival and prolonged treatment response for
patients facing this devastating and aggressive disease. These data
reinforce Imfinzi plus chemotherapy as an important new
standard of care for extensive-stage small cell lung cancer
patients, and this regimen offers patients convenient dosing every
four weeks during maintenance. We look forward to bringing the
benefits of Imfinzi to patients around the
world."
The second experimental arm in the CASPIAN trial testing
tremelimumab, an anti-CTLA4 monoclonal antibody, added
to Imfinzi and chemotherapy showed a trend towards OS,
but did not reach statistical significance compared to chemotherapy
alone.
Summary of updated results:
Data cut-off date was 27 January 2020. Formal statistical
analysis was completed at the time of the interim analysis per
trial protocol. Therefore, no formal testing for statistical
significance could be performed in this updated
analysis.
|
EPi + Imfinzi
(n=268)
|
EPi
(n=269)
|
OS (primary endpoint)
|
|
|
Number of deaths
|
210
(78.4%)
|
231
(85.9%)
|
Hazard ratio
|
0.75
(0.62, 0.91)
|
|
Nominal p-value
|
0.0032
|
|
Median in months
(95% CI)
|
12.9(11.3,
14.7)
|
10.5(9.3,
11.2)
|
OS rate (24 months)ii,iii
|
22.2%
|
14.4%
|
PFS (secondary endpoint)
|
|
|
Number (%) of patients with event
|
234
(87.3%)
|
236
(87.7%)
|
Hazard ratio (95% CI)
|
0.80
(0.66, 0.96)
|
|
Median in months
(95% CI)
|
5.1(4.7,
6.2)
|
5.4(4.8,
6.2)
|
PFS rate (6 months)
|
45.4%
|
45.8%
|
PFS rate (12 months)
|
17.9%
|
5.3%
|
PFS rate (24 months)iii
|
11.0%
|
2.9%
|
ORR (secondary endpoint)iv,v
|
|
|
Number (%) of patients with response
|
182
(67.9%)
|
156
(58.0%)
|
Odds ratio (95% CI)
|
1.53
(1.08, 2.18)
|
|
DoR at 24 monthsiii,iv
|
13.5%
|
3.9%
|
Ongoing Imfinzi, n
(%)iii
|
32
(12%)
|
0
|
i.
Etoposide plus investigator choice of carboplatin or cisplatin
chemotherapy.
ii.
OS rate is an estimated proportion of patients alive at 24
months.
iii.
Post-hoc analysis.
iv.
Confirmed responses according to investigator assessment per RECIST
v1.1.
v.
Unconfirmed ORR was a prespecified secondary endpoint per
protocol.
The safety and tolerability for Imfinzi plus chemotherapy was consistent with the
known safety profile of these medicines. Results showed 62.3% of
patients experienced a Grade 3 or 4 adverse event
with Imfinzi plus chemotherapy (all causes) versus 62.8%
with chemotherapy alone. The percentage of patients discontinuing
treatment (all causes) was 10.2% for Imfinzi plus chemotherapy and 9.4% for chemotherapy
alone.
Imfinzi in combination
with etoposide and either carboplatin or cisplatin is currently
under regulatory review for the treatment of ES-SCLC in the
1st-line setting in the EU and Japan.
Updated results from the CASPIAN trial were presented during
the 2020 American Society of Clinical Oncology ASCO20 Virtual
Scientific Program on 29 to 31 May 2020. Several presentations
featured during the meeting will showcase AstraZeneca's
leadership in lung cancer across early and late-stage disease and
reinforce the Company's biomarker-driven
approach.
Small cell lung cancer
Lung cancer is the leading cause of cancer death among both men and
women and accounts for about one fifth of all cancer
deaths.1 Lung
cancer is broadly split into NSCLC and SCLC, with about 15%
classified as SCLC.2 SCLC
is a highly aggressive, fast-growing form of lung cancer that
typically recurs and progresses rapidly despite initial response to
chemotherapy.3,4 About
two thirds of SCLC patients are diagnosed with extensive-stage
disease, in which the cancer has spread widely through the lung or
to other parts of the body.5 Prognosis
is particularly poor, as only 6% of all SCLC patients will be alive
five years after diagnosis.5
CASPIAN
CASPIAN was a randomised, open-label, multi-centre, global, Phase
III trial in the 1st-line treatment of 805 patients with ES-SCLC.
The trial compared Imfinzi in combination with etoposide and either
carboplatin or cisplatin chemotherapy, or Imfinzi and
chemotherapy with the addition of a second immunotherapy,
tremelimumab, versus chemotherapy alone. In the experimental arms,
patients were treated with four cycles of chemotherapy. In
comparison, the control arm allowed up to six cycles of
chemotherapy and optional prophylactic cranial irradiation. The
trial was conducted in more than 200 centres across 23 countries,
including the US, in Europe, South America, Asia and the Middle
East. The primary endpoint was OS in each of the two experimental
arms.
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 in the
curative-intent setting of unresectable, Stage III NSCLC after
chemoradiation therapy in the US, Japan, China, across the EU and
in many other countries, based on the Phase III PACIFIC
trial. Imfinzi is approved for the 1st-line treatment of
ES-SCLC in combination with chemotherapy in the US and
Singapore. 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,
SCLC, bladder cancer, head and neck cancer, liver cancer, biliary
tract cancer, cervical cancer and other solid
tumours.
Tremelimumab
Tremelimumab is a human monoclonal antibody and potential new
medicine that targets the activity of cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the
activity of CTLA-4, contributing to T-cell activation, priming the
immune response to cancer and fostering cancer cell
death. Tremelimumab is being tested in a clinical trial
programme in combination with Imfinzi in NSCLC, SCLC, bladder cancer, head and
neck cancer and liver cancer.
AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential
new medicines in late-stage development for the treatment of
different forms of lung cancer spanning different histologies,
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 the approved medicines Iressa (gefitinib) and Tagrisso and its ongoing Phase III trials LAURA, and
FLAURA2.6-8 We
are also committed to addressing tumour mechanisms of resistance
through the ongoing Phase II trials SAVANNAH and ORCHARD which
test Tagrisso in combination with savolitinib, a selective
inhibitor of c-MET receptor tyrosine kinase, along with other
potential new medicines. Enhertu a HER2-directed antibody drug conjugate is
in development for metastatic non-squamous HER2-overexpressing or
HER2-mutated NSCLC including trials in combination with other
anticancer treatments.
An extensive Immuno-Oncology development programme focuses on lung
cancer patients without a targetable genetic mutation which
represents up to three-quarters of all patients with lung
cancer.9 Imfinzi,
an anti-PDL1 antibody, is in development for patients with advanced
disease (Phase III trials POSEIDON and PEARL) and for patients in
earlier stages of disease including potentially-curative settings
(Phase III trials MERMAID-1, AEGEAN, ADJUVANT BR.31, PACIFIC-2,
PACIFIC-4, PACIFIC-5, and ADRIATIC) both as monotherapy and in
combination with tremelimumab and/or
chemotherapy. Imfinzi is also in development in the Phase II
trials NeoCOAST, COAST and HUDSON in combination with potential new
medicines from the early-stage pipeline
including Enhertu.
AstraZeneca's approach to Immuno-Oncology
Immuno-oncology (IO) is a therapeutic approach designed to
stimulate the body's immune system to attack tumours. The Company's
IO portfolio is anchored by immunotherapies that have been designed
to overcome anti-tumour immune suppression. AstraZeneca is invested
in using IO approaches that deliver long-term survival for new
groups of patients across tumour types.
The Company is pursuing a comprehensive clinical-trial programme
that includes Imfinzi as a monotherapy and in combination with
tremelimumab in multiple tumour types, stages of disease, and lines
of therapy, and where relevant 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 the IO portfolio
with radiation, chemotherapy, small targeted molecules from across
AstraZeneca's Oncology pipeline, and from research partners, may
provide new treatment options across a broad range of
tumours.
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 six new medicines
launched between 2014 and 2020, and a broad
pipeline of small molecules and biologics in development,
the Company is committed to advance oncology as a key growth driver
for AstraZeneca focused on lung, ovarian, breast and blood cancers.
In addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investment that
accelerate the delivery of our strategy, as illustrated by the
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.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) 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
& Immunology. Based in Cambridge, UK, AstraZeneca operates in
over 100 countries and its innovative medicines are used by
millions of patients worldwide. Please
visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. World Health Organization.
International Agency for Research on Cancer. Available at
http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed May 2020.
2. LUNGevity Foundation. Types of Lung Cancer. Available at
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed May 2020.
3. National Cancer Institute. NCI Dictionary - Small Cell Lung
Cancer. Available at
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer.
Accessed May 2020.
4. Kalemkerian GP, et al. Treatment Options for Relapsed Small-Cell
Lung Cancer: What Progress Have We Made? Journal of Oncology
Practice,
2018:14;369-370.
5. Cancer.Net. Lung Cancer - Small Cell. Available at
https://www.cancer.net/cancer-types/33776/view-all. Accessed May
2020.
6. 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.
7. 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.
8. 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.
9. Pakkala, S, et al. Personalized therapy for lung cancer:
striking a moving target. JCI Insight. 2018;3(15):e120858.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
29 May
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|