REG - AstraZeneca PLC - ODAC reviewed Imfinzi in resectable lung cancer

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26/07/2024 07:00

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RNS Number : 9254X  AstraZeneca PLC  26 July 2024

 

 

26 July 2024

 

FDA Advisory Committee reviewed Imfinzi for treatment of resectable non-small
cell lung cancer based on AEGEAN Phase III trial results

 

The Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee
(ODAC) acknowledged that AstraZeneca's Imfinzi (durvalumab) met the primary
endpoint of event-free survival (EFS) in the treatment of resectable non-small
cell lung cancer (NSCLC) based on the AEGEAN Phase III trial results with an
overall tolerable safety profile. In the trial, adult patients with resectable
early-stage (IIA-IIIB) NSCLC and no known epidermal growth factor receptor
(EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements were
treated with Imfinzi in combination with neoadjuvant chemotherapy before
surgery and as adjuvant monotherapy after surgery. The discussion noted that
while the contribution by phase of neoadjuvant and adjuvant components of the
perioperative regimen could not be clearly assigned based on the trial design,
this is an important potential regimen for patients.

 

The FDA accepted the supplemental Biologics License Application (sBLA) in
September 2023 for Imfinzi in this indication 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.

 

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: "The majority of patients with resectable lung cancer face recurrence of
their disease even after surgery and neoadjuvant chemotherapy. The Committee
acknowledged the potential to address this urgent unmet need with durvalumab
both before and after surgery, which can significantly increase the time
patients live without progression and recurrence events in this
curative-intent setting."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "The Committee's discussion of the AEGEAN data highlighted the
significant benefit delivered by this Imfinzi-based regimen for patients with
resectable lung cancer. We are committed to working closely with the FDA to
bring this novel immunotherapy option to patients that offers a flexible
chemotherapy backbone."

 

Results from a planned interim analysis of EFS from the AEGEAN trial 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).

 

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.

 

The ODAC provides the FDA with independent, expert advice and recommendations
on marketed and investigational medicines for use in the treatment of cancer.
The FDA will consider the feedback as it reviews the submission and is not
bound by the Committee's recommendation.

 

Imfinzi is approved
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/imfinzi-approved-in-us-for-biliary-tract-cancer.html#!)
in Switzerland and the UK for the treatment of adults with resectable NSCLC in
Stage II and III without known EGFR mutations or ALK rearrangements, based on
the AEGEAN results. Regulatory applications for Imfinzi in this setting are
also currently under review in the EU, China and several other countries.

 

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

Each year, there are an estimated 2.4 million people diagnosed with lung
cancer globally.(1) 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 36-46% of
patients with Stage II disease will survive for five years.(10) This decreases
to 24% for patients with Stage IIIA disease and 9% for patients with Stage
IIIB disease, reflecting a high unmet medical need.(10)

 

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 and regions 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 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
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

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

3.   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 July 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
(https://www.lungevity.org/lung-cancer-basics/screening-early-detection) .
Accessed July 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

 

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