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 June 2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Orpathys approved in China for lung cancer
23 June
2021 07:00 BST
Orpathys approved in China
for patients
with lung cancer and MET gene alterations
First-in-class approval in China in this setting and first
regulatory approval
for the oral, potent and highly selective MET tyrosine kinase
inhibitor
AstraZeneca
and HUTCHMED’s Orpathys (savolitinib) has been granted
conditional approval in China to treat patients with non-small cell
lung cancer (NSCLC) with
MET exon 14 skipping alterations who have progressed following
prior systemic therapy or are unable to receive
chemotherapy.
This approval follows a priority review designation by the Center
for Drug Evaluation of China’s National Medical Products
Administration (NMPA) and marks the first global regulatory
approval for the oral, potent, and highly selective MET tyrosine
kinase inhibitor (TKI).
More
than a third of the world’s lung cancer patients are in China
and, among those with NSCLC, approximately 2-3% have tumours with
MET exon 14 skipping alterations, a targetable mutation in the MET
gene.1-3
This mutation is more common (13-22%) among patients with pulmonary
sarcomatoid carcinoma (PSC), a rare and aggressive subtype of NSCLC
usually resistant to chemotherapy.1,4
The
approval by the NMPA was based
on positive results from a single-arm Phase II trial
conducted in China in patients with NSCLC with this mutation,
including patients with the PSC subtype. Orpathys demonstrated robust
anti-tumour activity based on an independent review of objective
response rate (ORR) in the trial’s primary endpoint and its
disease control rate (DCR). Continued approval is contingent upon
the successful completion of a confirmatory trial in this patient
population.
Dave
Fredrickson, Executive Vice President, Oncology Business Unit,
said: “This approval makes Orpathys the only targeted medicine
approved for these biomarker-selected patients in China, and it
adds another novel medicine to our already diverse lung cancer
portfolio. We are proud that this first-ever regulatory approval of
Orpathys is in China, where
we have a long-standing commitment to improving patient outcomes
and working with the right partners to achieve that goal. Alongside
HUTCHMED, we look forward to the continued development of this
medicine across a range of cancers where MET alterations and
amplification are drivers of tumour growth and treatment
resistance.”
Christian Hogg, Chief Executive Officer, HUTCHMED, said:
“It is with great pleasure that
today we announce the first regulatory approval of
Orpathys
globally, HUTCHMED’s third
self-discovered oncology drug to be commercialized. Our
collaboration with AstraZeneca in 2011 has been an important driver
in the development of this novel targeted oncology drug, involving
both a China-based biotech and a global pharmaceutical company.
This approval is a testament to the perseverance and scientific
ingenuity of this long-standing alliance, and we are hopeful that
this is only the beginning of the progress we can achieve for
patients with MET-altered tumours.”
In the
Phase II trial, at a median follow up of 17.6 months, Orpathys demonstrated an ORR of 42.9%
(95% confidence interval [CI] 31.1-55.3) and median
progression-free survival (PFS) of 6.8 months (95% CI 4.2-9.6) in
the overall trial population. PFS was clinically meaningful across
subgroups, and ORR results were consistent regardless of prior
treatment or tumour histology, including in patients with the PSC
subtype (40.0%, 95% CI 21.1-61.3) and patients with other NSCLC
subtypes (44.4%, 95% CI 29.6-60.0). DCR in the overall trial
population was 82.9% (95% CI 72.0-90.8).
The safety and tolerability profile of Orpathys was consistent with previous trials, and no new
safety signals were identified. Most adverse events (AEs) were
Grade 1–2 and resolved with dose modification or
discontinuation. Grade 3 or higher AEs occurred in 45.7% of
patients, and treatment-related serious AEs occurred in 24% of
patients. One treatment-related death was reported from tumour
lysis syndrome in a patient with PSC.
Results
from the Phase II trial were presented during the American Society
of Clinical Oncology ASCO20 Virtual Scientific Program in May 2020,
and updated results were published in The
Lancet Respiratory Medicine in
June 2021.
As part
of the joint global development programme with HUTCHMED,
Orpathys is being evaluated
in combination with Tagrisso and other medicines to address
tumour mechanisms of resistance in NSCLC in the ORCHARD and
SAVANNAH Phase II trials for the combinations to provide longer
duration of benefit, and as a treatment for other MET-driven
tumours, including papillary renal cell carcinoma, and gastric and
gastroesophageal junction cancers.
NSCLC, PSC and MET aberrations
Lung
cancer is the leading cause of cancer death among men and women,
accounting for about one-fifth of all cancer deaths.2 Lung cancer is
broadly split into NSCLC and small cell lung cancer, with 80-85%
classified as NSCLC.5 The majority of
NSCLC patients are diagnosed with advanced disease.6
PSC is
a rare subtype of NSCLC, comprising 0.3-3% of all lung
malignancies.7 Compared with other
NSCLC subtypes, PSC patients have a poorer prognosis and limited
treatment options.4,8-9
MET is
a tyrosine kinase receptor.10 While MET genetic
alterations are common in many solid tumours, MET exon 14 skipping
alterations are more frequently associated with lung cancer,
occurring in approximately 2-3% of patients with NSCLC and 13-22%
of patients with PSC.1,4,11 MET
amplification or overexpression is one of the mechanisms of
acquired resistance to epidermal growth factor receptor (EGFR) TKIs
for metastatic EGFR-mutated NSCLC.10
NCT02897479
The
single-arm, open-label Phase II trial NCT02897479 assessed the
efficacy and safety of Orpathys in the treatment of Chinese
patients with locally advanced or metastatic PSC or other NSCLC
subtypes with MET exon 14 skipping alterations who progressed on
prior treatment or were unable to receive
chemotherapy.
Patients
were treated with weight-based dosing of Orpathys once-daily oral tablets
(600mg/day or 400mg/day for patients weighing less than 50kg).
Treatment continued until disease progression, death, intolerable
toxicity, or discontinuation. The trial enrolled 70 patients across
multiple centres in China. The primary endpoint was ORR, and key
secondary endpoints were PFS, DCR and safety
assessment.
Orpathys
Orpathys (savolitinib) is an oral, potent, and highly
selective MET TKI that has demonstrated clinical activity in
advanced solid tumours. It blocks atypical activation of the MET
receptor tyrosine kinase pathway that occurs because of mutations
(such as exon 14 skipping alterations or other point mutations) or
gene amplification.
Orpathys is currently under clinical development for
multiple tumour types, including lung, kidney, and gastric cancers,
as a single treatment and in combination with other
medicines.
AstraZeneca and HUTCHMED collaboration
In
2011, AstraZeneca and HUTCHMED entered a global licensing agreement
to jointly develop and commercialise Orpathys. HUTCHMED is responsible for
the manufacturing and supply of Orpathys, and AstraZeneca is responsible
for its commercialisation in China and worldwide. Sales of
Orpathys will be recognised
by AstraZeneca.
AstraZeneca in lung cancer
AstraZeneca
is working to bring patients with lung cancer closer to cure
through the detection and treatment of early-stage disease, while
also pushing the boundaries of science to improve outcomes in the
resistant and advanced settings. By defining new therapeutic
targets and assessing innovative approaches, the Company aims to
match medicines to the patients who can benefit most.
The
Company’s comprehensive portfolio includes leading lung
cancer medicines and the next wave of innovations including
Tagrisso (osimertinib) and
Iressa (gefitinib);
Imfinzi (durvalumab) and
tremelimumab; Enhertu
(trastuzumab deruxtecan) and datopotamab deruxtecan in
collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration
with HUTCHMED; as well as a pipeline of potential new medicines and
combinations across diverse mechanisms of action.
AstraZeneca
is a founding member of the Lung Ambition
Alliance, a global coalition working to accelerate
innovation and deliver meaningful improvements for people with lung
cancer, including and beyond treatment.
AstraZeneca in oncology
AstraZeneca
is leading a revolution in oncology with the ambition to provide
cures for cancer in every form, following the science to understand
cancer and all its complexities to discover, develop and deliver
life-changing medicines to patients.
The
Company’s focus is on some of the most challenging cancers.
It is through persistent innovation that AstraZeneca has built one
of the most diverse portfolios and pipelines in the industry, with
the potential to catalyse changes in the practice of medicine and
transform the patient experience.
AstraZeneca
has the vision to redefine cancer care and, one day, eliminate
cancer as a cause of death.
AstraZeneca
AstraZeneca
(LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and
commercialisation of prescription medicines in Oncology and
BioPharmaceuticals, including 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.
Contacts
For
details on how to contact the Investor Relations Team, please click
here. For Media
contacts, click here.
References
1.
Vuong HG,
et al. Clinicopathological
implications of MET exon 14
mutations in non-small cell lung cancer – A systematic review
and meta-analysis. Lung
Cancer 2018; 123: 76-82.
2.
World Health
Organization. International Agency for Research on Cancer. Lung
Fact Sheet. Available at https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed June 2021.
3.
World Health
Organization. International Agency for Research on Cancer. Globocan
China Fact Sheet 2020. Available at http://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf.
Accessed June 2021.
4.
Liu X, et al. Next-generation sequencing of
pulmonary sarcomatoid carcinoma reveals high frequency of
actionable MET gene
mutations. J Clin Oncol
2016; 34: 794-802.
5.
LUNGevity
Foundation. Types of Lung Cancer. Available at https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed June 2021.
6.
Cagle P,
et al. Lung Cancer
Biomarkers: Present Status and Future Developments. Archives
Pathology Lab Med. 2013;137:1191-1198.
7.
Baldovini C,
et al. Approaches to tumor
classification in pulmonary sarcomatoid carcinoma. Lung Cancer (Auckl) 2019; 10:
131-49.
8.
Maneenil K,
et al. Sarcomatoid
carcinoma of the lung: the Mayo Clinic experience in 127 patients.
Clin Lung Cancer 2018; 19:
e323-e33.
9.
Martin LW,
et al. Sarcomatoid
carcinoma of the lung: a predictor of poor prognosis. Ann Thorac Surg 2007; 84:
973-80.
10.
Organ SL,
et al. An overview of the
c-MET signaling pathway. Ther Adv
Med Oncol 2011; 3(1Suppl): S7-S19.
11.
Salgia R,
et al. The promise of
selective MET inhibitors in non-small cell lung cancer with
MET exon 14 skipping.
Cancer Treat Rev 2020;
87:102022
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:
23 June
2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|