25 June 2024
Update on ADJUVANT BR.31
Phase III trial
of Imfinzi in
non-small cell lung cancer
High-level results from the ADJUVANT
BR.31 Phase III trial, sponsored by the Canadian Cancer Trials
Group (CCTG), showed Imfinzi (durvalumab) did not achieve
statistical significance for the primary endpoint of disease-free
survival (DFS) versus placebo in early-stage (IB-IIIA) non-small
cell lung cancer (NSCLC) after complete tumour resection in
patients whose tumours express PD-L1 on 25% or more tumour
cells.
Susan Galbraith, Executive Vice
President, Oncology R&D, AstraZeneca, said: "We are
disappointed in the ADJUVANT BR.31
results. Imfinzi has helped change the
treatment landscape and achieved multiple positive Phase III trials
for patients with earlier stages of lung cancer. We are committed to addressing the
remaining unmet need in lung cancer through our broad development
programme."
The safety profile for Imfinzi was consistent with its known
safety profile, and no new safety concerns were reported. The data
will be shared at a forthcoming medical meeting.
Imfinzi is the only approved
immunotherapy and the global standard of care in the
curative-intent setting of unresectable, Stage III
NSCLC in patients whose
disease has not progressed after chemoradiotherapy based on the
PACIFIC Phase III trial.
Imfinzi is also being
investigated as monotherapy and in combinations in several other early-stage lung cancer settings,
including in medically inoperable or
unresected Stage I-II NSCLC (PACIFIC-4) and unresectable, Stage III
NSCLC (PACIFIC-5, 8 and 9).
Notes
Lung
cancer
Each year, there are an estimated 2.4
million people diagnosed with lung cancer globally. Lung cancer is
the leading cause of cancer death among both men and women,
accounting for about one-fifth of all cancer deaths.1-2
Lung cancer is broadly split into NSCLC and small cell lung cancer
(SCLC), with 80-85% of patients diagnosed with
NSCLC.3-4
The majority of NSCLC patients are
diagnosed with advanced disease while approximately 25-30% present
with resectable disease at diagnosis.5-6 Early-stage
lung cancer diagnoses are often only made when the cancer is found
on imaging for an unrelated condition.7-8
The majority of patients with
resectable disease eventually develop recurrence despite complete
tumour resection and adjuvant chemotherapy.9 Only around
58% of patients with Stage IB disease will survive for five years.
This decreases to 36-46% for patients with Stage II and 24% for
patients with Stage IIIA disease, reflecting a high unmet medical
need.10
ADJUVANT BR.31
ADJUVANT BR.31 is a randomised,
multi-centre, double-blind Phase III trial sponsored by CCTG
evaluating Imfinzi in the
adjuvant treatment of 1,415 patients with Stage IB (≥4cm), II or
IIIA (Seventh Edition AJCC Cancer Staging Manual) NSCLC following
complete tumour resection with or without adjuvant chemotherapy.
AstraZeneca provided Imfinzi and support for the trial.
Patients were randomised 2:1 to receive a 20mg/kg IV infusion of
Imfinzi or placebo every
four weeks for up to 48 weeks.
The trial is being conducted at 269
centres across 19 countries and regions including in Canada, the
US, Australia, Europe and Asia. The primary endpoint is DFS in
patients whose tumours express PD-L1 on 25% or more tumour cells
and do not have known common EGFR mutations or ALK
rearrangements. Key secondary endpoints
include DFS in patients whose tumours express
PD-L1 on 1% or more of cells and in patients regardless of PD-L1
tumour cell expression status, overall survival and safety.
DFS is defined as time from randomisation to date of first
recurrence, new cancer or death from any cause and is recognised as
an important clinical measure by both physicians and
patients.
Canadian Cancer Trials Group (CCTG)
CCTG is an academic cancer clinical
trials research cooperative that runs Phase I-III trials to test
anti-cancer and supportive therapies at over 85 hospitals and
cancer centres across Canada. From the operations centre at Queen's
University, CCTG has supported more than 600 trials enrolling
100,000 patients from 40 countries on 6 continents through a global
network of 20,000 investigators and clinical trial staff. CCTG is a
national program of the Canadian Cancer Society, and their aim is
to improve survival and quality of life for all people with
cancer.
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.
Imfinzi is the only approved
immunotherapy and the global standard of care in the
curative-intent setting of unresectable, Stage III NSCLC in
patients whose disease has not progressed after chemoradiation
therapy. Imfinzi is also
approved for the treatment of extensive-stage SCLC and in
combination with a short course of Imjudo (tremelimumab) and chemotherapy for
the treatment of metastatic NSCLC.
Imfinzi also demonstrated
statistically significant and clinically meaningful event-free
survival results in patients with resectable early-stage NSCLC
based on the AEGEAN Phase III trial. Imfinzi in combination with
neoadjuvant chemotherapy before surgery and as adjuvant monotherapy
after surgery is approved for patients in Switzerland based on this
trial.
In limited-stage SCLC, Imfinzi demonstrated statistically
significant and clinically meaningful improvements in the dual
primary endpoints of OS and progression-free survival (PFS)
compared to placebo in patients who had not progressed following
standard-of-care concurrent chemoradiotherapy in the ADRIATIC Phase
III trial.
In addition to its indications in
lung cancers, Imfinzi is
approved in combination with chemotherapy (gemcitabine plus
cisplatin) 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 combination with chemotherapy (carboplatin plus
paclitaxel) followed by Imfinzi monotherapy in primary
advanced or recurrent endometrial cancer that is mismatch repair
deficient in the US.
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, breast cancer, several gastrointestinal
and gynaecologic cancers, and other solid
tumours.
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's innovative medicines are sold in more
than 125 countries and used by millions of patients worldwide.
Please visit
astrazeneca.com and follow the
Company on social media
@AstraZeneca.
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References
1. 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 June 2024.
2. World Health Organization. International Agency
for Research on Cancer. World Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf.
Accessed June 2024.
3. LUNGevity Foundation. Types of Lung Cancer.
Available at:
https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed June 2024.
4. Cheema PK, et al. Perspectives on treatment
advances for stage III locally advanced unresectable non-small-cell
lung cancer. Curr Oncol.
2019;26(1):37-42.
5. Cagle PT, et
al. Lung Cancer
Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med.
2013;137(9):1191-1198.
6. Le Chevalier T. Adjuvant Chemotherapy for
Resectable Non-Small-Cell Lung Cancer: Where is it Going?
Ann Oncol. 2010;21(suppl
7):vii196-198.
7. Sethi S, et al. Incidental Nodule Management -
Should There Be a Formal Process? J Thorac Dis. 2016:8(Suppl
6);S494-S497.
8. LUNGevity Foundation. Screening and Early
Detection. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection..
Accessed June 2024.
9. Pignon JP, et al. Lung Adjuvant Cisplatin Evaluation:
A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol.
2008;26(21):3552-3559.
10.
Goldstraw P, et al. The
IASLC Lung Cancer Staging Project: proposals for the revision of
the TNM stage groupings in the forthcoming (seventh) edition of the
TNM Classification of malignant tumours. J Thorac
Oncol. 2007;2(8):706-14.
Adrian Kemp
Company
Secretary
AstraZeneca PLC