REG - AstraZeneca PLC - Imfinzi approved in US for resectable lung cancer

AstraZenecaAnnouncement

16/08/2024 07:00

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RNS Number : 6767A  AstraZeneca PLC  16 August 2024

16 August 2024

 

Imfinzi approved in the US for the treatment of resectable

non-small cell lung cancer before and after surgery

Based on AEGEAN Phase III trial results which showed Imfinzi-based regimen
reduced the risk of recurrence, progression or death by 32% vs. neoadjuvant
chemotherapy alone

 

AstraZeneca's Imfinzi (durvalumab) in combination with chemotherapy has been
approved in the US for the treatment of adult patients with resectable
early-stage (IIA-IIIB) non-small cell lung cancer (NSCLC) and no known
epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma
kinase (ALK) rearrangements. In this regimen, patients are treated with
Imfinzi in combination with neoadjuvant chemotherapy before surgery and as
adjuvant monotherapy after surgery.

 

The approval by the Food and Drug Administration (FDA) was based on positive
results from the pivotal AEGEAN trial
(https://www.astrazeneca.com/media-centre/press-releases/2023/imfinzi-based-treatment-before-and-after-surgery-reduced-the-risk-of-disease-recurrence-progression-events-or-death-in-resectable-non-small-cell-lung-cancer.html)
, which were published in The New England Journal of Medicine
(https://www.nejm.org/) in October 2023. Results from a planned interim
analysis of event-free survival (EFS) showed a statistically significant and
clinically meaningful 32% reduction in the risk of recurrence, progression
events or death versus chemotherapy alone in patients treated with the
Imfinzi-based regimen before and after surgery (32% data maturity; EFS hazard
ratio of 0.68; 95% confidence interval  CI  0.53-0.88; p=0.003902).

 

In a final analysis of pathologic complete response (pCR), treatment with
Imfinzi plus neoadjuvant chemotherapy before surgery resulted in a pCR rate of
17.2% versus 4.3% for patients treated with neoadjuvant chemotherapy alone
(difference in pCR 13.0%; 95% CI 8.7-17.6).

 

Each year, there are an estimated 2.4 million people diagnosed with lung
cancer globally, with approximately 235,000 new diagnoses expected in the US
in 2024.(1-2) Around 25-30% of all patients with NSCLC, the most common form
of lung cancer, are diagnosed early enough to have surgery with curative
intent.(3-4) However, the majority of patients with resectable disease will
develop recurrence and only 36-46% of patients with Stage II disease will
survive for five years.(5-6) This decreases to 24% for patients with Stage
IIIA disease and 9% for patients with Stage IIIB disease, reflecting a high
unmet medical need.(6)

 

John V. Heymach, MD, PhD, Professor and Chair Thoracic/Head and Neck Medical
Oncology, The University of Texas MD Anderson Cancer Center in Houston, Texas,
said: "This approval brings an important new treatment option that should
become a backbone combination approach for patients with resectable non-small
cell lung cancer, who have historically faced high rates of recurrence even
after chemotherapy and surgery. When added both before and after surgery,
durvalumab delivered a significant and meaningful improvement in outcomes in
this curative-intent setting."

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "Today's approval of Imfinzi in resectable early-stage lung
cancer builds on its strong foundation of changing clinical practice in
unresectable Stage III disease. We remain committed to bringing novel
approaches like AEGEAN to early lung cancer settings where cure is the goal of
treatment."

 

Imfinzi was generally well tolerated, and no new safety signals were observed
in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to
neoadjuvant chemotherapy was consistent with the known profile for this
combination and did not compromise patients' ability to complete surgery
versus chemotherapy alone.

 

Imfinzi is also approved in the UK, Switzerland and Taiwan (China) in this
setting based on the AEGEAN results. Regulatory applications are also
currently under review in the EU, China and several other countries in this
indication.

 

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.

 

Notes

 

Lung cancer

Lung cancer is the leading cause of cancer death among both men and women,
accounting for about one-fifth of all cancer deaths.(1,7) Lung cancer is
broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% of
patients diagnosed with NSCLC.(8-9)

 

Early-stage lung cancer diagnoses are often only made when the cancer is found
on imaging for an unrelated condition.(10-11) The majority of patients with
resectable disease eventually develop recurrence despite complete tumour
resection and adjuvant chemotherapy.(5)

 

AEGEAN

AEGEAN is a randomised, double-blind, multi-centre, placebo-controlled global
Phase III trial evaluating Imfinzi as perioperative treatment for patients
with resectable Stage IIA-IIIB (Eighth Edition AJCC Cancer Staging Manual)
NSCLC, irrespective of PD-L1 expression. Perioperative therapy includes
treatment before and after surgery, also known as neoadjuvant/adjuvant
therapy. In the trial, 802 patients were randomised to receive a 1500mg fixed
dose of Imfinzi plus chemotherapy or placebo plus chemotherapy every three
weeks for four cycles prior to surgery, followed by Imfinzi or placebo every
four weeks (for up to 12 cycles) after surgery. Patients with known EGFR or
ALK genomic tumour aberrations were excluded from the primary efficacy
analyses.

 

In the AEGEAN trial, the primary endpoints were pCR, defined as no viable
tumour in the resection specimen (including lymph nodes) following neoadjuvant
therapy, and EFS, defined as the time from randomisation to an event like
tumour recurrence, progression precluding definitive surgery, or death. Key
secondary endpoints were major pathologic response, defined as residual viable
tumour of less than or equal to 10% in the resected primary tumour following
neoadjuvant therapy, disease-free survival, overall survival (OS), safety and
quality of life. The final pathologic response analyses were performed after
all patients had the opportunity for surgery and pathology assessment per the
trial protocol. The trial enrolled participants from 264 centres in more than
25 countries including in the US, Canada, Europe, South America 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.

 

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. Imfinzi in combination
with chemotherapy (etoposide and either carboplatin or cisplatin) 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.

 

In limited-stage SCLC, Imfinzi demonstrated statistically significant and
clinically meaningful improvements in the dual primary endpoints of OS and
progression-free survival 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, bladder 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 (http://www.astrazeneca.com/)  and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
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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
(https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf)
. Accessed August 2024.

2.   American Cancer Society. Key Statistics for Lung Cancer. Available at:
https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
(https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html#:~:text=The%20American%20Cancer%20Society%27s%20estimates,men%20and%2059%2C280%20in%20women)
. Accessed August 2024.

3.   Cagle PT, et al. Lung Cancer Biomarkers: Present Status and Future
Developments. Arch Pathol Lab Med. 2013;137(9):1191-1198.

4.   Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell
Lung Cancer: Where is it Going? Ann Oncol. 2010;21(suppl 7):vii196-198.

5.   Pignon JP, et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis
by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552-3559.

6.   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.

7.   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
(https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf)
. Accessed August 2024.

8.   LUNGevity Foundation. Types of Lung Cancer. Available at:
https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer
(https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer)
. Accessed August 2024.

9.   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. 

10.  Sethi S, et al. Incidental Nodule Management - Should There Be a Formal
Process? J Thorac Dis. 2016:8(Suppl 6);S494-S497.   

11.  LUNGevity Foundation. Screening and Early Detection. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection
(https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection)
. Accessed August 2024.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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