FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of June 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Datroway approved in US for EGFRm lung cancer
24 June 2025
Datroway approved in the US for patients with
previously treated advanced EGFR-mutated non-small cell lung
cancer
Based on TROPION-Lung05 results and supported by data from
TROPION-Lung01
First and only TROP2-directed therapy approved in the US for the
treatment of lung cancer
Datroway (datopotamab
deruxtecan or Dato-DXd) has been approved in the US for the
treatment of adult patients with locally advanced or
metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who
have received prior EGFR-directed therapy and platinum-based
chemotherapy.
This indication is approved under accelerated approval based on
objective response rate (ORR) and duration of response (DoR).
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial.
The approval follows Priority
Review and Breakthrough Therapy
Designation by the Food
and Drug Administration (FDA) based on results from a subgroup
analysis of the TROPION-Lung05 Phase
II trial and supported by data from the TROPION-Lung01 Phase
III trial.
Jacob Sands, MD, Medical Oncology, Dana-Farber Cancer Institute and
investigator in both trials, said: "Addressing disease progression
in patients with advanced EGFR-mutated lung cancer after prior targeted therapy
and chemotherapy is very challenging with limited later-line
treatment options available. The US approval of datopotamab
deruxtecan introduces a novel and needed treatment option to
patients with advanced disease."
Dave Fredrickson, Executive Vice President, Oncology Haematology
Business Unit, AstraZeneca, said: "This first approval
of Datroway in lung cancer provides a much-needed option
to patients with advanced EGFR-mutated lung cancer whose disease has become
resistant to past treatments, regardless of the driving mutation.
We have long supported patients with EGFR-mutated lung cancer and are proud to bring
another innovative treatment option to this
community."
Ken Keller, Global Head of Oncology Business, and President and
CEO, Daiichi Sankyo, Inc, said: "With today's accelerated
approval, Datroway is now the first TROP2-directed medicine
available for certain patients in the US living with lung cancer.
We remain committed to our extensive clinical development programme
to further identify where Datroway may be used in other types of lung and
breast cancer."
Andrea E. Ferris, President and CEO, LUNGevity, said: "For people
with advanced EGFR-mutated non-small cell lung cancer whose disease
progresses on initial treatments, additional options are limited.
Today's approval of Datroway offers a new treatment option for patients
whose disease has progressed following treatment with
an EGFR-directed therapy and
chemotherapy."
In TROPION-Lung05 and TROPION-Lung01, Datroway demonstrated a confirmed ORR of 45% (95%
confidence interval [CI]: 35-54) in patients with previously
treated locally advanced or metastatic EGFR-mutated NSCLC (n=114) as assessed by blinded
independent central review (BICR). Complete responses were seen in
4.4% of patients and partial responses were seen in 40% of
patients. The median DoR was 6.5 months (95% CI:
4.2-8.4).
The safety profile of Datroway was evaluated in a pooled analysis of 125
patients in the TROPION-Lung05, TROPION-Lung01 and
TROPION-PanTumor01 trials. The safety profile observed across these
trials was consistent with the known profile of this medicine with
no new safety concerns identified.
Datroway is a specifically
engineered TROP2-directed DXd antibody drug conjugate (ADC)
discovered by Daiichi Sankyo and being jointly developed and
commercialised by AstraZeneca and Daiichi
Sankyo.
AstraZeneca and Daiichi Sankyo are
evaluating Datroway alone and with Tagrisso (osimertinib) in other advanced or
metastatic EGFR-mutated NSCLC settings in
the TROPION-Lung14 and TROPION-Lung15 Phase
III trials.
Financial considerations
Following approval in the US, an amount of $45 million is due from
AstraZeneca to Daiichi Sankyo as a milestone payment for
the locally advanced or metastatic EGFR-mutated NSCLC indication. Sales
of Datroway in the US are recognized by Daiichi Sankyo.
For further details on the financial arrangements, please consult
the collaboration agreement from July
2020.
Notes
Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in
2022.1 Lung
cancer is broadly split into small or non-small cell lung cancer,
the latter accounting for about 87% of cases.2 Approximately
10 to 15% of patients with NSCLC in the US and Europe, and 30 to
40% of patients in Asia have an EGFR mutation.3,4 The
majority of EGFR mutations occur in tumours of nonsquamous
histology.5 TROP2
is a protein broadly expressed in the majority of NSCLC
tumours.6
For patients with tumours that have an EGFR mutation, the established 1st-line treatment
in the metastatic setting includes EGFR-directed therapy with or without platinum-based
chemotherapy.7 While
these therapies have improved outcomes in earlier lines of
treatment, most patients eventually experience disease progression
and receive subsequent therapies.8-11
TROPION-Lung05
TROPION-Lung05 is a
global, multicentre, single-arm, open-label Phase II trial
evaluating the efficacy and safety of Datroway in patients with locally advanced or
metastatic NSCLC with actionable genomic alterations who have
progressed on at least one EGFR-directed therapy and platinum-based chemotherapy.
Patients receiving up to four prior lines of treatment with tumours
with one or more genomic alterations
including EGFR, ALK, ROS1, NTRK, BRAF, RET or MET were eligible for the
trial.
The primary endpoint of TROPION-Lung05 is ORR as assessed by BICR.
Secondary efficacy endpoints include DoR, disease control rate
(DCR), clinical benefit rate, PFS, time to response (TTR), OS and
safety. TROPION-Lung05 enrolled 137 patients globally in Asia,
Europe and North America. For more information,
visit ClinicalTrials.gov.
Primary results from TROPION-Lung05 were published in
the Journal of Clinical
Oncology in January
2025.
TROPION-Lung01
TROPION-Lung01 is a
global, randomised, multicentre, open-label Phase III trial
evaluating the efficacy and safety of Datroway versus docetaxel in adult patients with
locally advanced or metastatic NSCLC with and without actionable
genomic alterations who require systemic therapy following prior
treatment. Patients with actionable genomic alterations were
previously treated with an approved targeted therapy and
platinum-based chemotherapy. Patients without known actionable
genomic alterations were previously treated, concurrently or
sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1
inhibitor.
The dual primary endpoints of TROPION-Lung01 are PFS as assessed by
BICR and OS. Key secondary endpoints include investigator-assessed
PFS, ORR, DoR, TTR, and DCR as assessed by both BICR and
investigator, and safety. TROPION-Lung01 enrolled 590 patients in
Asia, Europe, North America, Oceania and South America. For more
information visit ClinicalTrials.gov.
Primary results from TROPION-Lung01, as presented at
the ESMO 2023 Congress, showed Datroway demonstrated a statistically significant
improvement in PFS over docetaxel. OS results
were presented at
the IASLC 2024 World Conference on Lung Cancer hosted by the
International Association for the Study of Lung Cancer and
simultaneously published in
the Journal of Clinical
Oncology in September
2024.
TROPION-PanTumor01
TROPION-PanTumor01 is a
first-in-human, open-label, two-part, multicentre Phase I trial
evaluating the safety and preliminary efficacy
of Datroway in patients with advanced solid tumours that
have relapsed or are refractory to standard treatment or for which
no standard treatment is available. The dose escalation portion of
the trial enrolled patients with NSCLC to assess the safety and
tolerability of Datroway to determine the recommended dose for
expansion (6mg/kg). The dose expansion part of TROPION-PanTumor01
enrolled several different cohorts including patients with NSCLC,
triple-negative breast cancer (TNBC), HR-positive, HER2-negative
breast cancer, small cell lung cancer, urothelial, gastric,
pancreatic, castration resistant prostate and oesophageal
cancer.
Safety endpoints include dose-limiting toxicities and serious
adverse events. Efficacy endpoints include ORR, DoR, TTR, PFS and
OS. Pharmacokinetic, biomarker and immunogenicity endpoints also
are being evaluated. TROPION-PanTumor01 enrolled 890 patients in
Asia and North America. For more information,
visit ClinicalTrials.gov.
Datroway
Datroway (datopotamab
deruxtecan; datopotamab deruxtecan-dlnk in the US only) is a
TROP2-directed ADC. Designed using Daiichi Sankyo's proprietary DXd
ADC Technology, Datroway is one of six DXd ADCs in the oncology
pipeline of Daiichi Sankyo, and one of the most advanced programmes
in AstraZeneca's ADC scientific platform. Datroway is comprised of a humanised anti-TROP2 IgG1
monoclonal antibody, developed in collaboration with Sapporo
Medical University, attached to a number of topoisomerase I
inhibitor payloads (an exatecan derivative, DXd) via
tetrapeptide-based cleavable linkers.
Datroway is approved in
more than 30 countries worldwide for the treatment of adult
patients with unresectable or metastatic HR-positive, HER2-negative
(IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received
prior endocrine-based therapy and chemotherapy for unresectable or
metastatic disease based on the results from
the TROPION-Breast01 trial.
Datroway is available in
the US under accelerated approval for the treatment of adult
patients with locally advanced or
metastatic EGFR-mutated NSCLC who have received
prior EGFR-directed therapy and platinum-based chemotherapy
based on results from the TROPION-Lung05 and TROPION-Lung01 trials.
Continued approval for this indication in the US may be contingent
upon verification and description of clinical benefit in a
confirmatory trial. Datroway is approved in Russia for the same
population.
Datroway clinical development
programme
A comprehensive global clinical development programme is
underway with more than 20 trials evaluating the efficacy and
safety of Datroway across multiple cancers, including NSCLC,
TNBC and HR-positive, HER2-negative breast cancer. The
programme includes eight Phase III trials in lung cancer and five
Phase III trials in breast cancer
evaluating Datroway as a monotherapy and in combination with
other anticancer treatments in various
settings.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration
to jointly develop and commercialise Enhertu in March
2019 and Datroway in July
2020, except in Japan where
Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi
Sankyo is responsible for the manufacturing and supply
of Enhertu and Datroway.
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 and Iressa (gefitinib); Imfinzi and Imjudo; Enhertu (trastuzumab deruxtecan)
and Datroway in collaboration 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 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.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. World Health Organization. Global
Cancer Observatory: Lung. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed May 2025.
2. American Cancer Society. Key
Statistics for Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html.
Accessed May 2025.
3. Szumera-Ciećkiewicz A, et
al. EGFR mutation testing on
cytological and histological samples in non-small cell lung cancer:
a Polish, single institution study and systematic review of
European incidence. Int J Clin
Exp Pathol.
2013;6(12): 2800-2812.
4. Ellison G, et
al. EGFR mutation
testing in lung cancer: a review of available methods and their use
for analysis of tumour tissue and cytology
samples. J Clin
Pathol.
2013;66(2): 79-89.
5. Prabhakar C. Epidermal growth
factor receptor in non-small cell lung
cancer. Translational
Lung Cancer Research. 2015;4(2):
110-118.
6. Mito R, et al. Clinical impact of
TROP2 in non-small lung cancers and its correlation with abnormal
P53 nuclear accumulation. Pathol
Int.
2020;70(5): 287-294.
7. American Cancer Society. Targeted
Drug Therapy for Non-Small Cell Lung Cancer. Available
at: https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html.
Accessed May 2025.
8. Chen R, et al. Emerging
therapeutic agents for advanced non-small cell lung
cancer. J Hematol
Oncol.
2020:13(1): 58.
9. Majeed U, et al. Targeted therapy
in advanced non-small cell lung cancer: current advances and future
trends. J Hematol
Oncol.
2021;14(1): 108.
10. Morgillo F, et al. Mechanisms of
resistance to EGFR-targeted drugs: lung
cancer. ESMO
Open. 2016;1:
e000060.
11. Han B, et al. Efficacy of
pemetrexed-based regimens in advanced non-small cell lung cancer
patients with activating epidermal growth factor receptor mutations
after tyrosine kinase inhibitor failure: a systematic
review. Onco Targets
Ther. 2018;11:
2121-9.
Matthew Bowden
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
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AstraZeneca
PLC
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Date: 24 June 2025
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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