A retrospective observational study to evaluate demographic/clinical characteristics, treatments, patterns of therapy, and outcomes of patients with advanced non-small cell lung cancer (aNSCLC) in England

Takeda Development Centre Americas, Inc. (hereafter referred to as "Takeda") requires Evidera Ltd to have access to NHS England Data for the purpose of the following research project:

A retrospective observational study to evaluate demographic/clinical characteristics, treatments, patterns of therapy, and outcomes of patients with advanced non-small cell lung cancer (aNSCLC) in England.

The following is a summary of the aims of the study provided on behalf of Takeda.

• Describe the demographic and clinical characteristics of patients with aNSCLC who have received treatment with tyrosine kinase inhibitors (TKI), or checkpoint inhibitors (CPI) followed by at least one subsequent line of therapy (LOT).

• Describe patterns and sequences of anti-cancer treatments in patients with aNSCLC who have received treatment with a TKI or CPI followed by at least one subsequent LOT (for up to 4 LOTs).

• Estimate overall survival and time to next treatment in patients with aNSCLC who have received treatment with a TKI or CPI followed by at least one subsequent LOT.

The following NHS England Data will be accessed:

• NDRS Hospital Episode Statistics-

o Linked Admitted Patient Care (APC)

o Linked Outpatients (OP)

NDRS HES data will be requested to describe the metastasis sites and history of radiotherapy and surgery.

• NCRAS (Cancer registry) data will be used to study the real-world overall survival. It will also be used to define the study cohorts and its subgroups (namely, the treatment cohorts), and to describe the sociodemographic and clinical characteristics of the patients, as well as cancer disease history. The morphology subtype (squamous/non squamous) will also be identified using this dataset, for stratified analyses.

• NDRS Systemic Anti-Cancer Therapy Dataset (SACT) - will be used to describe patients' clinical characteristics, to aid in selection of regimens that were specifically administered for aNSCLC, to select the treatment cohorts to be studied, to define the index date, to identify the LOT, to ascertain treatment sequences for treatment pattern analysis, and to study an outcome of interest (i.e., real-world time-to-next treatment). In addition, identified TKI treatment will be used as a proxy for EGFR and ALK+ mutations that will serve for analysis stratification. LOT received will also be used as a stratification variable.

• NDRS Somatic Molecular Dataset – will be used to look at oncogenic drivers (e.g., EGFR mutation, ALK mutation, KRAS mutation, BRAF mutation, etc.), which are important clinical factors for treatment selection and will be needed to determine whether treatment patterns identified within the data align with recommended treatments for patients with these mutations.

• NDRS National Radiotherapy Dataset (RTDS) - will be used to describe the history of radiotherapy and its use during the follow-up period.

The level of the Data will be Pseudonymised.

The Data will be minimised as follows:

• Limited to a study cohort identified by NHS England as meeting the following criteria:

All patients over 18 years of age diagnosed with advanced/metastatic aNSCLC on or after 01/01/2016 up to 6 months before the latest available. Treated with systemic anticancer therapy (SACT) for their disease and whose index line of therapy (LOT) has been initiated between 01/01/2016 and at least 6 months before the latest available data.

Baseline data will be obtained 5 years prior to diagnosis.

Takeda Development Center Americas, Inc. is the study sponsor and the controller responsible for ensuring that the Data will only be processed for the purposes described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(f) - processing is necessary for the purposes of the legitimate interests pursued by the controller or by a third party.

Takeda Development Centre Americas, Inc. has determined the processing is necessary for its legitimate interests because it allows the researcher to analyse linked cancer registry data to understand treatment patterns and real-world outcomes for advanced non-small cell lung cancer (aNSCLC) patients in England. By studying therapy effectiveness and variations in treatment response, they aim to refine strategies that improve patient care. The NCRAS datasets offer unique insights not available in standard UK healthcare data, enabling a more precise understanding of cancer progression.

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding is provided by Takeda. The funding is specifically for the project described. The funder will have no ability to suppress or otherwise limit the publication of findings.

Evidera Ltd is a processor acting under the instructions of Takeda. Evidera Ltd’s role is limited to designing the study, conducting data analysis, and drafting the study report.

Takeda is a pharmaceutical company and will be conducting this research to better understand the current treatment patterns and outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and how they respond to therapy. Takeda's commercial interest is based on the fact that the results will provide insights to enhance the design of clinical trials of immunotherapies that Takeda has in development for various solid cancers including NSCLC.

There is a commercial element to this research. Evidera Ltd benefits commercially as a global contract research organisation. Conducting this research contributes to Evidera's revenue and professional portfolio.

Takeda’s commercial benefit lies in using the research findings to support the development and strategic positioning of its COBRA and STING oncology platforms. By analysing treatment patterns and outcomes in patients with advanced non-small cell lung cancer (aNSCLC), Takeda gains valuable insights that can:

-Inform future clinical trial designs.

-Strengthen submissions for health technology assessments

-Identify patient populations most likely to benefit from its immunotherapy products.

-Enhance the market readiness and reimbursement potential of its cancer therapies.

-These insights help Takeda optimise its product development and improve the likelihood of successful market access across the UK and Europe.

Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out.

No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA).

NHS England will provide the relevant records from the requested datasets to Evidera Ltd. The Data will contain no direct identifying data items. The Data will be pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient.

The Data will not be transferred to any other location.

The Data will be stored on servers at the Evidera Ltd offices in England.

The Data will be accessed by authorised personnel via remote access.

Evidera Ltd must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

- Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

- Access controls granting users the minimum level of access required are in place;

- Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data;

- Multifactor authentication (MFA) is required for remote access;

- Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

- All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

The Data will not leave England/Wales at any time.

Access is restricted to employees of Evidera Ltd.

Employees of Takeda are only permitted to access anonymised data including information derived from NHS England Data. Such datasets will adhere to the relevant small number suppression rules to minimise the risk of individuals being identified.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

The Data will not be linked with any other data.

There will be no requirement and no attempt to reidentify individuals when using the Data.

Researchers from Evidera Ltd will process the Data for the purposes described above.

The expected outputs of the processing will be:

• A report of findings to Takeda after completion of the data analysis.

• Submissions to peer reviewed journals will occur after the completion of the study report.

• Presentations at high-impact real-world evidence and oncology conferences in 2026. These conferences will facilitate engagement with the scientific and clinical community.

• Key findings will be summarized in public reports and dashboards that will be made available on the Takeda website.

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Where possible, results will be published via the open access route to ensure free access to all stakeholders in England and Wales, including patients, the public, researchers, clinicians, and policy makers.

• Key findings will be summarized in public reports and dashboards that will be made available on the organisation's website. These will provide easily accessible and understandable information for a broad audience, including health and social care professionals in England and Wales.

Based on an assumed data delivery date in Q3 2025, Evidera Ltd estimates a data analysis completion in Q4 2025 and a study report delivered in Q1 2026. Once the study report has been drafted, manuscripts and abstracts will be prepared for submission to peer-reviewed journals and conferences in 2026.

The use of this data could:

• Improve Decision-Making – Policymakers, healthcare providers, and researchers will gain evidence-based insights into treatment patterns and patient outcomes, helping refine treatment strategies.

• Enhance Healthcare Planning – The study will identify regional and national trends in aNSCLC management, informing resource allocation and service provision.

• Advancement in Treatments – By highlighting unmet needs in disease progression and survival, the findings will support the development of new treatments and interventions.

• Support for Future Research – The results will contribute to broader cancer research, fostering innovation and improvements in oncology and public health.

The benefits to patients include:

• Personalised Care – Understanding treatment responses within different subgroups will help tailor therapies for better outcomes.

• Improved Survival Rates – Identifying effective treatment approaches can lead to better survival prospects for aNSCLC patients.

• Greater Patient Empowerment – Insights into treatment efficacy will enable patients to make more informed healthcare decisions.

• Access to Better Care – Research-driven improvements in aNSCLC management will enhance the quality of care available to patients across England and Wales.

The expected benefits can be measured by:

1. The number of scientific publications

2. Number of submissions to regulatory/payers/HTA incorporating relevant research findings

3. Citations of study publications by other researchers

4. Number of NICE evidence reviews that have cited findings from this study

5. Number of consultations and workshops held with clinicians, policy makers and patient groups

6. Number of conference presentations

7. Number of other dissemination materials published on the Takeda or other websites.

It is envisioned that results will be presented in medical journals and, where possible, results will be published via the open access route to ensure that all stakeholders, including clinicians, policymakers, and patients, can access the findings freely. There will also be communication of results with Key Opinion Leaders in the UK to help interpret the findings and facilitate their application in clinical practice. Finally, a lay summary of the key findings from this study will be published on the Takeda or other publicly accessible website.

Yielded Benefits is not a requirement for new applications.