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 November 2024
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Dato-DXd new BLA submitted, NSQ BLA withdrawn
12 November 2024
Datopotamab deruxtecan new BLA
submitted for accelerated approval in the US for patients with
previously treated advanced EGFR-mutated non-small cell lung
cancer
AstraZeneca and Daiichi Sankyo's new application is based on the
TROPION-Lung05 Phase II trial and supported by data from additional
trials including TROPION-Lung01
Previously submitted BLA based on TROPION-Lung01 Phase III trial
for patients with nonsquamous NSCLC has been voluntarily
withdrawn
AstraZeneca and Daiichi Sankyo have submitted a new Biologics
License Application (BLA) for accelerated approval in the US for
datopotamab deruxtecan (Dato-DXd) for the treatment of adult
patients with locally advanced or metastatic epidermal growth
factor receptor-mutated (EGFR) non-small cell lung cancer (NSCLC) who have
received prior systemic therapies, including
an EGFR-directed therapy.
The companies have voluntarily withdrawn the BLA in the US for
datopotamab deruxtecan for patients with advanced or metastatic
nonsquamous NSCLC based on the TROPION-Lung01 Phase III
trial.
The decision to submit a new BLA for EGFR-mutated NSCLC and withdraw the previously
submitted BLA for nonsquamous NSCLC was informed by feedback from
the US Food and Drug Administration (FDA).
The new BLA is based on results from the TROPION-Lung05 Phase II
trial and supported by data from the TROPION-Lung01 Phase III and
TROPION-PanTumor01 Phase I trials. New results from a pooled
analysis of patients with previously
treated EGFR-mutated NSCLC in the TROPION-Lung05 and
TROPION-Lung01 trials will be featured in a late-breaking
presentation at the upcoming European Society for Medical Oncology
(ESMO) Asia 2024 Congress (LBA7).
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "TROPION-Lung01 was designed to test the
potential to improve upon standard-of-care chemotherapy in a broad,
previously treated, advanced lung cancer patient population. The
results, together with data from TROPION-Lung05, showed an
especially pronounced benefit for patients with
an EGFR mutation which informed our discussions with
the FDA and the decision to seek accelerated approval of
datopotamab deruxtecan in this patient population. TROPION-Lung01
has also provided exciting exploratory data supporting our
biomarker development, which will be validated in ongoing and
planned Phase III lung cancer trials."
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said:
"Treating EGFR-mutated non-small cell lung cancer is incredibly
challenging following disease progression given that the complexity
and variability of these mutations often lead to resistance. The
potential approval of datopotamab deruxtecan could offer renewed
hope for patients with this formidable
disease."
Datopotamab deruxtecan is a specifically engineered TROP2-directed
DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and
being jointly developed by AstraZeneca and Daiichi
Sankyo.
AstraZeneca and Daiichi Sankyo are evaluating datopotamab
deruxtecan alone and with Tagrisso (osimertinib) as treatment for patients with
advanced or metastatic EGFR-mutated nonsquamous NSCLC in the
ongoing TROPION-Lung14 and TROPION-Lung15 Phase
III trials. In addition, ongoing Phase III trials in 1st-line
advanced or metastatic nonsquamous NSCLC, AVANZAR and TROPION-Lung10,
have the potential to validate the QCS (quantitative continuous
scoring) biomarker for TROP2 identified in an exploratory analysis
of TROPION-Lung01.
An additional trial in patients with biomarker-positive tumours in
the 2nd-line nonsquamous NSCLC setting is also
planned.
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-cell lung cancer (SCLC) or
NSCLC, the latter accounting for about 80% of
cases.2 Approximately
10-15% of patients with NSCLC in the US and Europe, and 30-40% of
patients in Asia have an EGFR mutation.3,4 The
majority of EGFR mutations occur in tumours of nonsquamous
histology.5
For patients with tumours that have an EGFR mutation, the established 1st-line treatment
in the metastatic setting is an EGFR-tyrosine kinase inhibitor
(TKI).6 While EGFR-TKIs
have improved outcomes in the 1st-line setting, most patients
eventually experience disease progression and receive
chemotherapy.7-10
TROP2 is a protein broadly expressed in the majority of NSCLC
tumours.11 There
is currently no TROP2-directed ADC approved for the treatment of
lung cancer.6,12
TROPION-Lung05
TROPION-Lung05 is a
global, multicentre, single-arm, open-label Phase II trial
evaluating the efficacy and safety of datopotamab deruxtecan in
patients with locally advanced or metastatic NSCLC with actionable
genomic alterations who have progressed on or after one regimen of
platinum-based chemotherapy and at least one TKI (with or without
other systemic therapies). 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 trial endpoint of TROPION-Lung05 is objective response
rate (ORR) as assessed by blinded independent central review
(BICR). Secondary efficacy endpoints include duration of response
(DoR), disease control rate (DCR), clinical benefit rate,
progression-free survival (PFS), time to response (TTR), overall
survival (OS) and safety.
TROPION-Lung05 enrolled 137 patients globally in Asia, Europe and
North America. For more information visit ClinicalTrials.gov.
TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label
Phase III trial evaluating the efficacy and safety of datopotamab
deruxtecan 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 approximately 600 patients in Asia, Europe,
North America, Oceania and South America. For more information
visit ClinicalTrials.gov.
Primary PFS and interim OS results from TROPION-Lung01
were presented at
the ESMO 2023 Congress. Final OS results
were presented at 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 datopotamab deruxtecan 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 datopotamab deruxtecan to
determine the recommended dose for expansion (6 mg/kg). The dose
expansion part of TROPION-PanTumor01 is enrolling several different
cohorts including patients with NSCLC, triple-negative breast
cancer (TNBC), HR-positive, HER2-low or negative breast cancer,
SCLC, urothelial, gastric, pancreatic, castration-resistant
prostate and esophageal 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 approximately 900 patients in Asia and
North America. For more information visit ClinicalTrials.gov.
Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational
TROP2-directed ADC. Designed using Daiichi Sankyo's proprietary DXd
ADC Technology, datopotamab deruxtecan 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.
Datopotamab deruxtecan is comprised of a humanized 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.
A comprehensive global clinical development programme is underway
with more than 20 trials evaluating the efficacy and safety of
datopotamab deruxtecan across multiple cancers, including NSCLC,
TNBC and HR-positive, HER2-low or negative breast cancer. The
programme includes seven Phase III trials in lung cancer and five
Phase III trials in breast cancer evaluating datopotamab deruxtecan
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 (trastuzumab deruxtecan)
in March
2019 and datopotamab
deruxtecan 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 datopotamab
deruxtecan.
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 (durvalumab) and Imjudo (tremelimumab); 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 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 November 2024.
2.
Cancer.net. Lung Cancer - Non-Small Cell: Statistics. Available
at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer.
Accessed November 2024.
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. Translational Lung Cancer Research. 2015; 4(2),
110-118.
6.
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 November 2024.
7. Chen R, et al. Emerging
therapeutic agents for advanced non-small cell lung cancer. J
Hematol Oncol. 2020;13(1):58.
8. 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.
9. Morgillo
F, et al. ESMO Open. 2016;1:e000060. Available
at: https://esmoopen.bmj.com/content/1/4/e000060.
Accessed November 2024.
10. Han B, et al. Onco
Targets Ther. 2018;11:2121-9. Available
at: https://www.dovepress.com/oncotargets-and-therapy-journal.
Accessed November 2024.
11. 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.
12. Rodríguez-Abreau D, et
al. Pemetrexed plus platinum with or
without pembrolizumab in patients with previously untreated
metastatic nonsquamous NSCLC: protocol-specified final analysis
from KEYNOTE-189. Ann Onc. 2021 Jul;32(7):
881-895.
Adrian Kemp
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:
12 November 2024
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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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