05 April 2024
Imfinzi
significantly
improved overall survival and progression-free survival for
patients with limited-stage small cell lung cancer in ADRIATIC
Phase III trial
First and only immunotherapy
to demonstrate survival benefit in this setting in a global Phase
III trial
Positive high-level results of the
ADRIATIC Phase III trial showed AstraZeneca's Imfinzi
(durvalumab) demonstrated a statistically
significant and clinically meaningful improvement in the dual
primary endpoints of overall survival (OS) and progression-free
survival (PFS) in patients with limited-stage small cell lung
cancer (LS-SCLC) who had not progressed following concurrent
chemoradiotherapy (cCRT) compared to placebo after cCRT.
Small cell lung cancer (SCLC) is a
highly aggressive form of lung cancer that typically recurs and
progresses rapidly despite initial response to chemotherapy and
radiotherapy in LS-SCLC patients.1,2 The prognosis is
particularly poor for LS-SCLC, as only 15-30% of these patients will be alive five
years after diagnosis.3
Suresh Senan, PhD, Professor of
Clinical Experimental Radiotherapy at the Amsterdam University
Medical Center, The Netherlands, and principal
investigator in the trial said:
"Many patients treated for limited-stage small cell lung cancer
face disease recurrence and the standard of care has remained
unchanged for decades. ADRIATIC is the first global Phase III
immunotherapy trial to deliver significant, clinically meaningful
improvement in survival in this setting, marking a breakthrough for patients with this
devastating disease."
Susan Galbraith, Executive Vice
President, Oncology R&D, AstraZeneca, said: "These exciting
results build on the transformative efficacy of Imfinzi in extensive-stage small cell
lung cancer and demonstrate the potential to bring a
curative-intent immunotherapy treatment to this earlier-stage
setting of small cell lung cancer for the first
time. These data, together with the PACIFIC
data in unresectable, Stage III non-small cell lung cancer,
underscore the pioneering role of Imfinzi in the treatment of early lung
cancer following chemoradiotherapy."
The safety profile for Imfinzi was consistent with its known
profile, and no new safety signals were identified.
These data will be presented at a
forthcoming medical meeting and shared with global regulatory
authorities.
The second experimental arm testing
the efficacy of Imjudo
(tremelimumab) added to Imfinzi as a secondary endpoint
remains blinded and will continue to the next planned
analysis.
Imfinzi is approved in the US,
EU, Japan, China and many other countries around the world for the
treatment of extensive-stage SCLC (ES-SCLC) based on the CASPIAN
Phase III trial. Imfinzi
is also the only approved immunotherapy and the
global standard of care in the curative-intent setting of
unresectable, Stage III non-small cell lung
cancer (NSCLC) in patients whose disease
has not progressed after CRT based on the PACIFIC Phase III
trial.
Notes:
Small cell lung cancer
Lung cancer is the leading cause of
cancer death among men and women and accounts for about one-fifth
of all cancer deaths.4 Lung cancer is broadly split into
NSCLC and SCLC, with about 15% of cases classified as
SCLC.5
LS-SCLC (Stage I-III) is classified
as SCLC that is generally only in one lung or one side of the
chest.6 LS-SCLC accounts for approximately 30% of SCLC
diagnoses and the prognosis remains poor despite curative-intent
treatment with standard-of-care cCRT.7
ADRIATIC
The ADRIATIC trial is a randomised, double-blind,
placebo-controlled, multi-centre global Phase III trial evaluating
Imfinzi monotherapy and
Imfinzi plus Imjudo versus placebo in the treatment
of 730 patients with LS-SCLC who had not progressed
following cCRT. In the experimental arms, patients
were randomised to receive a 1500mg fixed dose of Imfinzi with or without Imjudo 75mg every four weeks for up to
four doses/cycles each, followed by Imfinzi every four weeks for up to 24
months.
The dual primary endpoints are PFS
and OS for Imfinzi
monotherapy versus placebo.
Key secondary endpoints included OS and PFS for
Imfinzi plus Imjudo versus placebo, safety and
quality of life measures.
The trial includes 164 centres in 19
countries across North and South America, Europe
and Asia.
Imfinzi
Imfinzi (durvalumab) is a human
monoclonal antibody that binds to the PD-L1 protein and blocks the
interaction of PD-L1 with the PD-1 and CD80 proteins, countering
the tumour's immune-evading tactics and releasing the inhibition of
immune responses.
In addition to its indications in
unresectable, Stage III NSCLC and ES-SCLC, Imfinzi is currently approved in a
number of countries in combination with a short course of
Imjudo and chemotherapy
for the treatment of metastatic NSCLC.
Imfinzi is also approved in a
number of countries in combination with chemotherapy in locally
advanced or metastatic biliary tract cancer and in combination with
Imjudo in unresectable
hepatocellular carcinoma (HCC). Imfinzi is also approved as a
monotherapy in unresectable HCC in Japan and the EU and in
previously treated patients with advanced bladder cancer in a small
number of countries.
Since the first approval in May
2017, more than 220,000 patients have been treated with
Imfinzi. As part of a
broad development programme, Imfinzi is being tested as a single
treatment and in combinations with other anti-cancer treatments for
patients with SCLC, NSCLC, bladder cancer, breast cancer, several
gastrointestinal cancers and other solid tumours.
Imjudo
Imjudo (tremelimumab) is a
human monoclonal antibody that targets the activity of cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4). Imjudo blocks the activity of CTLA-4,
contributing to T-cell activation, priming the immune response to
cancer and fostering cancer cell death.
In addition to its approved
indications in combination with Imfinzi in liver and lung cancers, the
combination of Imjudo and
Imfinzi is being evaluated
across multiple tumour types including locoregional HCC (EMERALD-3)
and bladder cancer (VOLGA and NILE).
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 investigating
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 and Imjudo; 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 immuno-oncology
(IO)
AstraZeneca is a pioneer in
introducing the concept of immunotherapy into dedicated clinical
areas of high unmet medical need. The Company has a comprehensive
and diverse IO portfolio and pipeline anchored in immunotherapies
designed to overcome evasion of the anti-tumour immune response and
stimulate the body's immune system to attack tumours.
AstraZeneca strives to redefine
cancer care and help transform outcomes for patients with Imfinzi
as a monotherapy and in combination with Imjudo as well as other novel
immunotherapies and modalities. The Company is also investigating
next-generation immunotherapies like bispecific antibodies and
therapeutics that harness different aspects of immunity to target
cancer, including cell therapy and T cell engagers.
AstraZeneca is pursuing an
innovative clinical strategy to bring IO-based therapies that
deliver long-term survival to new settings across a wide range of
cancer types. The Company is focused on exploring novel combination
approaches to help prevent treatment resistance and drive longer
immune responses. With an extensive clinical programme, the Company
also champions the use of IO treatment in earlier disease stages,
where there is the greatest potential for cure.
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, Rare Diseases, 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 social media
@AstraZeneca.
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References
1. 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 April
2024.
2. Qin A and Kalemkerian
GP. Treatment Options for Relapsed Small-Cell Lung Cancer: What
Progress Have We Made? J Oncol
Pract. 2018;14(6):369-370.
3. Bebb DG, et al.
Symptoms and Experiences with Small Cell Lung Cancer: A Mixed
Methods Study of Patients and Caregivers. Pulm Ther. 2023:9;435-450.
4. World Health Organization. International Agency for Research
on Cancer. Lung Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed April 2024.
5. LUNGevity Foundation.
Types of Lung Cancer. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed April 2024.
6. American Cancer Society. Treatment Choices by Stage for Small
Cell Lung Cancer. Available at:
https://www.cancer.org/cancer/lung-cancer/treating-small-cell/by-stage.html.
Accessed April
2024.
7. Senan S, et al.
ADRIATIC: A phase III trial of durvalumab ± tremelimumab after
concurrent chemoradiation for patients with limited stage small
cell lung cancer. Ann
Oncol. 2019;30(suppl. 2):ii25.
Adrian Kemp
Company Secretary
AstraZeneca PLC