REG - AstraZeneca PLC - Update on PACIFIC-2 Phase III trial for Imfinzi

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14/11/2023 07:15

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RNS Number : 3039T  AstraZeneca PLC  14 November 2023

14 November 2023

 

Update on PACIFIC-2 Phase III trial of Imfinzi concurrently administered with
platinum-based chemoradiotherapy in unresectable, Stage III non-small cell
lung cancer

 

The PACIFIC-2 Phase III trial for Imfinzi (durvalumab) concurrently
administered with chemoradiotherapy (CRT) did not achieve statistical
significance for the primary endpoint of progression-free survival (PFS)
versus CRT alone for the treatment of patients with unresectable, Stage III
non-small cell lung cancer (NSCLC).

 

Imfinzi sequentially administered after platinum-based CRT is the established,
global standard of care for the treatment of unresectable, Stage III NSCLC
based on the results of the PACIFIC Phase III trial. The PACIFIC-2 trial was
initiated to evaluate concurrent Imfinzi administration with CRT, with the aim
of addressing patients who progress or discontinue treatment during CRT and
are therefore ineligible for the PACIFIC regimen.

 

Initial analysis of the safety and tolerability for Imfinzi and CRT in this
patient population showed that the profiles were broadly consistent with the
known profiles of these treatments, although there was an increased rate of
infection observed during the concurrent treatment period in the experimental
arm.

 

Jeffrey D. Bradley, MD, Vice Chair of Proton Therapy & Technology
Development, Penn Medicine, Philadelphia and principal investigator for the
trial said: "While the PACIFIC-2 trial results did not show what we hoped,
the PACIFIC regimen remains the standard of care for patients with
unresectable, Stage III non-small cell lung cancer. As a community, we will
take insights from these results to advance future research."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "Our goal with the PACIFIC-2 trial was to address a remaining unmet need
for patients in this setting by introducing immunotherapy even earlier and
concurrently administering Imfinzi with chemoradiotherapy. While today's
results did not reach statistical significance, we will learn from this trial
and we remain committed to improving patient outcomes by expanding the benefit
of immunotherapy to lung cancer patients across treatment settings."

 

AstraZeneca has several ongoing registrational trials focused on testing
Imfinzi in early stages of lung cancer, including in resectable NSCLC
(ADJUVANT BR.31), medically inoperable or unresected Stage I-II NSCLC
(PACIFIC-4) and unresectable, Stage III NSCLC (PACIFIC-5, 8 and 9), and in
limited-stage small-cell lung cancer (SCLC) (ADRIATIC).

 

Notes:

 

Stage III NSCLC

Each year, an estimated 2.2 million people are 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) Lung cancer
is broadly split into NSCLC and SCLC, with 80-85% classified as NSCLC, making
it the most common form of lung cancer.(2-3) Approximately one in three
patients with NSCLC are diagnosed at Stage III (locally advanced), where the
majority of tumours are unresectable (cannot be removed with surgery).(4-5)

 

Stage III NSCLC is divided into three subcategories (IIIA, IIIB and IIIC),
defined by how much the cancer has spread locally.(6) In contrast to Stage IV,
when cancer has spread to other parts of the body (metastasised), the majority
of Stage III patients are currently treated with curative intent.(3,6)

 

PACIFIC-2

The PACIFIC-2 trial was a Phase III, randomised, double-blind,
placebo-controlled, multi-centre international study of Imfinzi concurrently
administered with platinum-based CRT in patients with unresectable, Stage III
NSCLC. In the trial, patients were randomised 2:1 to receive a 1,500mg fixed
dose of Imfinzi or placebo every four weeks starting at the beginning of
definitive CRT. Patients continued to receive Imfinzi or placebo as
consolidation treatment after CRT until disease progression.

 

The trial was conducted at 88 centres across more than 20 countries involving
328 patients. The primary endpoint was PFS, and key secondary endpoints
included overall survival, objective response rate and duration of response.

 

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 based on the PACIFIC
Phase III trial results which have been confirmed in the real-world setting in
the PACIFIC-R study.

 

Imfinzi is also approved in the US, EU, Japan, China and many other countries
around the world for the treatment of extensive-stage SCLC based on the
CASPIAN Phase III trial. Additionally, Imfinzi is approved in combination with
a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of
metastatic NSCLC in the US, EU and Japan based on the POSEIDON 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 in the US, EU, Japan and several other
countries based on the TOPAZ-1 and HIMALAYA Phase III trials, respectively.
Imfinzi is also approved in previously treated patients with advanced bladder
cancer in a small number of countries.

 

Since the first approval in May 2017, more than 200,000 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, several gastrointestinal cancers
and other solid tumours.

 

In 2023, AstraZeneca announced positive results for several Phase III trials
evaluating Imfinzi in various combinations, including in ovarian (DUO-O) and
endometrial (DUO-E) cancers with Lynparza (olaparib), gastric and
gastroesophageal cancer (MATTERHORN) and resectable NSCLC (AEGEAN).

 

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 aims to reimagine cancer care and help transform outcomes for
patients with Imfinzi as a single treatment and in combination
with Imjudo as well as other novel immunotherapies and modalities. The
Company is also exploring next-generation immunotherapies like bispecific
antibodies and therapeutics that harness different aspects of immunity to
target cancer.

 

AstraZeneca is boldly 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. 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 (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 Organisation. International Agency for Research on Cancer.
Lung Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf
(https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf) .
Accessed October 2023.

2.   LUNGevity Foundation. Types of Lung Cancer. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer
(https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer)
. Accessed October 2023.

3.   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.

4.     Hansen RN, et al. Long-term survival trends in patients with
unresectable stage III non-small cell lung cancer receiving chemotherapy and
radiation therapy: a SEER cancer registry analysis. BMC Cancer.
2020;20(1):276.

5.     Provencio M, et al. Inoperable stage III non-small cell lung
cancer: Current treatment and role of vinorelbine. J Thorac Dis.
2011;3(3):197-204.

6.   ASCO. Cancer.net. Lung Cancer - Non-Small Cell. Available at:
https://www.cancer.net/cancer-types/lung-cancer/view-all
(https://www.cancer.net/cancer-types/lung-cancer/view-all) . Accessed October
2023.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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