NIS to Examine the Effectiveness of TDC in Patients With Metastatic Non-squamous NSCLC and High-risk Genetic Alterations (NAUTIC)

Prospective Non-interventional Study (NIS) to Examine the Effectiveness of Tremelimumab + Durvalumab + Platinum Chemotherapy (TDC) in Patients With Metastatic Non-squamous NSCLC and High-risk Genetic Alterations

This prospective, multicenter, non-interventional study (NIS) in Germany aims to collect real-life data of patients with non-squamous (NSQ) metastatic non-small cell lung cancer (mNSCLC) (incl. large cell neuroendocrine carcinoma (LCNEC) if considered NSCLC-like by the treating physician) for whom 1st line treatment initiation with tremelimumab and durvalumab in combination with a platinum-based chemotherapy (TDC) according to marketing authorization was scheduled. The study aims to describe the effectiveness with respect to mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS), Serine/threonine kinase 11 (STK11), Kelch-like ECH-associated protein 1 (KEAP1), and Tumor protein p53 (TP53) as well as expression of Thyroid transcription factor 1 (TTF-1) and Programmed death-ligand 1 (PD-L1) in routine clinical practice. The generated data aims to deepen the understanding of optimal, biomarker-guided treatment strategies for NSQ mNSCLC in distinct subgroups with a high medical need.

Study Overview

• Status: Recruiting
• Conditions: Non-squamous Metastatic Non-Small-Cell Lung Carcinoma

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Germany
  • Bad Homburg, Germany
    • Recruiting
    • Research Site
  • Berlin, Germany
    • Recruiting
    • Research Site
  • Bremen, Germany
    • Recruiting
    • Research Site
  • Celle, Germany
    • Withdrawn
    • Research Site
  • Chemnitz, Germany
    • Recruiting
    • Research Site
  • Cologne, Germany
    • Recruiting
    • Research Site
  • Deggendorf, Germany
    • Recruiting
    • Research Site
  • Frankfurt, Germany
    • Recruiting
    • Research Site
  • Georgsmarienhütte, Germany
    • Recruiting
    • Research Site
  • Gera, Germany
    • Withdrawn
    • Research Site
  • Goslar, Germany
    • Recruiting
    • Research Site
  • Greifswald, Germany
    • Recruiting
    • Research Site
  • Halle-Dolau, Germany
    • Recruiting
    • Research Site
  • Hanover, Germany
    • Recruiting
    • Research Site
  • Herne, Germany
    • Recruiting
    • Research Site
  • Hösbach, Germany
    • Recruiting
    • Research Site
  • Koln-Mehrheim, Germany
    • Recruiting
    • Research Site
  • Mainz, Germany
    • Recruiting
    • Research Site
  • Marburg, Germany
    • Recruiting
    • Research Site
  • Münnerstadt, Germany
    • Recruiting
    • Research Site
  • Neuss, Germany
    • Recruiting
    • Research Site
  • Offenbach, Germany
    • Recruiting
    • Research Site
  • Querfurt, Germany
    • Recruiting
    • Research Site
  • Ravensburg, Germany
    • Recruiting
    • Research Site
  • Rüsselsheim am Main, Germany
    • Recruiting
    • Research Site
  • Treuenbrietzen, Germany
    • Recruiting
    • Research Site
  • Ulm, Germany
    • Recruiting
    • Research Site
  • Wiesbaden, Germany
    • Recruiting
    • Research Site
  • Zwickau, Germany
    • Recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years) with a histologically or cytologically confirmed NSQ mNSCLC (incl. LCNEC if considered NSCLC-like by the treating physician), planned treatment initiation with TDC according to applicable Summary of product characteristics (SmPCs) within routine clinical practice and initiated molecular gene panel analysis (including KRAS, STK11, KEAP1, and TP53) as well as PD-L1 and TTF-1 expression analyses are eligible for enrolment.

Eligible patients will be included into the study after and independently of the treating physician's treatment and diagnostic decisions but no later than 21 days after application of the first TDC treatment cycle.

Description

Inclusion Criteria:

• Aged ≥ 18 years
• Decision to start first-line (1L) treatment with TDC according to the current SmPCs
• Histologically or cytologically confirmed diagnosis of NSQ mNSCLC (incl. LCNEC if considered NSCLC-like by the treating physician)
• No sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) alterations
• Molecular Next Generation Sequencing (NGS) panel as per institutional standard has been initiated (including the following genes: KRAS, STK11, KEAP1, and TP53)
• TTF-1 expression analysis has been initiated
• PD-L1 expression analysis has been initiated
• Women of childbearing potential must use effective contraception during treatment with durvalumab and for at least 3 months after the last dose of durvalumab
• Ability to understand the study concept
• Provision of signed informed consent form in accordance with applicable local provisions

Exclusion Criteria:

• Current participation in interventional clinical trials
• Contraindications according to current SmPCs
• Any active tumor other than metastatic NSCLC

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Two-year real-world overall survival (rwOS) rate of patients with NSQ mNSCLC in patients with mutations in KRAS	rwOS rate (percentage of patients being alive derived by Kaplan-Meier methods) at 24 months in patients with mutations in KRAS. Patients without a date of death will be censored at last activity in the database, or the end of the study period, whichever occurs first.	Time from patient's index date until death by any cause, up to 24 months
Two-year real-world overall survival (rwOS) rate of patients with NSQ mNSCLC in patients with mutations in STK11	rwOS rate (percentage of patients being alive derived by Kaplan-Meier methods) at 24 months in patients with mutations in STK11. Patients without a date of death will be censored at last activity in the database, or the end of the study period, whichever occurs first.	Time from patient's index date until death by any cause, up to 24 months
Two-year real-world overall survival (rwOS) rate of patients with NSQ mNSCLC in the total study population	rwOS rate (percentage of patients being alive derived by Kaplan-Meier methods) at 24 months in the total study population. Patients without a date of death will be censored at last activity in the database, or the end of the study period, whichever occurs first.	Time from patient's index date until death by any cause, up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world overall survival (rwOS) in a subgroup of patients with mutation in KRAS	rwOS rate (percentage of patients being alive derived by Kaplan-Meier methods) at 6, 12 and 18 months	6, 12 and 18 months
Median overall survival (mOS) in a subgroup of patients with mutation in KRAS	OS is defined as the time from the date of first documented dose of TDC until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. Median OS will be calculated using the Kaplan-Meier technique.	up to 24 months
Real-world overall survival (rwOS) in a subgroup of patients with mutation in STK11	rwOS rate (percentage of patients being alive derived by Kaplan-Meier methods) at 6, 12 and 18 months	6, 12 and 18 months
Median overall survival (mOS) in a subgroup of patients with mutation in STK11	OS is defined as the time from the date of first documented dose of TDC until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. Median OS will be calculated using the Kaplan-Meier technique.	up to 24 months
Real-world treatment response of TDC, as judged by the treating physician	Treatment response in terms of overall response rate (ORR), being defined as the proportion of patients with complete response (CR) or partial response (PR) as best overall response, CR or PR, at ≥1 visit during treatment with TDC.	up to 24 months
Safety: Collection of Adverse Events (AE)	Safety evaluated based on type of Adverse Event (AE), intensity, causal relationship to treatment, duration, handling, outcome, and seriousness.	up to 24 months
Real-world overall survival (rwOS) in the total study population	rwOS rate (percentage of patients being alive derived by Kaplan-Meier methods) at 6, 12 and 18 months	6, 12 and 18 months
Median overall survival (mOS) in the total study population	OS is defined as the time from the date of first documented dose of TDC until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. Median OS will be calculated using the Kaplan-Meier technique.	up to 24 months
Duration of response (DoR)	Duration of response (DoR), being defined as time from documented CR or PR until documentation of progressive disease (PD), or death by any cause will be analyzed with Kaplan-Meier methods. Patients without documentation of PD will be censored with their last date in the database known to be without PD, or the end of study date, whichever occurs first. Patients who received a subsequent line mNSCLC therapy after TDC before disease progression or death will be censored with the start date of this new therapy.	up to 24 months
Real-world progression-free survival (rwPFS)	rwPFS is defined as time from patient's index date until first date of PD or death by any cause and will be analyzed by Kaplan-Meier methods.	up to 24 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Durvalumab; NSCLC,; mNSCLC,; KRAS,; STK11,; KEAP1,; TP53,; POSEIDON,; Tremelimumab,
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Genetic Diseases, Inborn; Respiratory Tract Diseases; Peripheral Nervous System Diseases; Lung Diseases; Neurodegenerative Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Carcinoma, Bronchogenic; Bronchial Neoplasms; Nervous System Malformations; Polyneuropathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carcinoma, Non-Small-Cell Lung; Hereditary Sensory and Autonomic Neuropathies
• Other Study ID Numbers: D419MR00003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca (AZ) group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.