REG - AstraZeneca PLC - Datroway approved in US for EGFRm lung cancer

AstraZenecaAnnouncement

Tue 07:00

For best results when printing this announcement, please click on link below:
https://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20250624:nRSX0652Oa&default-theme=true

RNS Number : 0652O  AstraZeneca PLC  24 June 2025

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
(https://www.astrazeneca.com/media-centre/press-releases/2025/datopotamab-deruxtecan-granted-priority-review-in-the-us-for-patients-with-previously-treated-advanced-egfr-mutated-non-small-cell-lung-cancer.html)
and Breakthrough Therapy Designation
(https://www.astrazeneca.com/media-centre/press-releases/2024/datopotamab-deruxtecan-granted-breakthrough-therapy-designation-us-patients-previously-treated-advanced-egfr-mutated-non-small-cell-lung-cancer.html)
by the Food and Drug Administration (FDA) based on results from a subgroup
analysis of the TROPION-Lung05 (https://clinicaltrials.gov/study/NCT04484142)
Phase II trial and supported by data from the TROPION-Lung01
(https://clinicaltrials.gov/study/NCT04656652) 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 (https://clinicaltrials.gov/study/NCT06350097) and
TROPION-Lung15 (https://clinicaltrials.gov/study/NCT06417814) 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
(https://www.daiichisankyo.com/files/news/pressrelease/pdf/007172/20200727_E.pdf)
.

 
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 (https://clinicaltrials.gov/study/NCT04484142) 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 (https://clinicaltrials.gov/study/NCT04484142) .

 

Primary results from TROPION-Lung05 were published
(https://ascopubs.org/doi/10.1200/JCO-24-01349) in the Journal of Clinical
Oncology in January 2025.

 
TROPION-Lung01

TROPION-Lung01 (https://clinicaltrials.gov/study/NCT04656652) 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
(https://clinicaltrials.gov/study/NCT04656652) .

 

Primary results from TROPION-Lung01, as presented
(https://www.astrazeneca.com/media-centre/press-releases/2023/datopotamab-deruxtecan-improved-progression-free-survival-vs-chemotherapy-in-tropion-lung01-phase-iii-trial.html)
at the ESMO 2023 Congress, showed Datroway demonstrated a statistically
significant improvement in PFS over docetaxel. OS results were presented
(https://www.astrazeneca.com/media-centre/press-releases/2024/dato-dxd-showed-median-overall-survival-of-146-months-in-patients-with-advanced-nsclc-in-tropion-lung01-phase-iii-trial.html)
at the IASLC 2024 World Conference on Lung Cancer hosted by the International
Association for the Study of Lung Cancer and simultaneously published
(https://ascopubs.org/doi/10.1200/JCO-24-01544) in the Journal of Clinical
Oncology in September 2024.

 
TROPION-PanTumor01

TROPION-PanTumor01
(https://clinicaltrials.gov/study/NCT03401385?term=TROPION-PanTumor01&rank=1)
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
(https://clinicaltrials.gov/study/NCT03401385?term=TROPION-PanTumor01&rank=1)
.

 

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
(https://www.clinicaltrials.gov/study/NCT05104866) 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
(https://www.daiichisankyo.com/media/press_release/detail/index_3199.html) and
Datroway in July 2020
(https://www.daiichisankyo.com/media/press_release/detail/index_3126.html) ,
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 (https://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. Global Cancer Observatory: Lung. 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 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
(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
(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

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCFJMLTMTATBIA