Clinical trial NCT06494540: NIS to Examine the Effectiveness of TDC in Patients With Metastatic Non-squamous NSCLC and High-risk Genetic Alterations
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-squamous Metastatic Non-Small-Cell Lung Carcinoma
Keywords: NSCLC,
mNSCLC,
KRAS,
STK11,
KEAP1,
TP53,
POSEIDON,
Tremelimumab,
Durvalumab
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-07-10
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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)
* Treatment-naïve for metastatic disease
* 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

Primary outcomes:
measure: Two-year real-world overall survival (rwOS) rate of patients with NSQ mNSCLC in the overall study population
timeFrame: Time from patient's index date until death by any cause, up to 24 months
measure: Two-year real-world overall survival (rwOS) rate of patients with NSQ mNSCLC in patients with mutations in KRAS
timeFrame: Time from patient's index date until death by any cause, up to 24 months
measure: Two-year real-world overall survival (rwOS) rate of patients with NSQ mNSCLC in patients with mutations in STK11
timeFrame: Time from patient's index date until death by any cause, up to 24 months
Secondary outcomes:
measure: Real-world overall survival (rwOS) in the overall study population
timeFrame: 6, 12 and 18 months
measure: Median overall survival (mOS) in the overall study population
timeFrame: up to 24 months
measure: Real-world overall survival (rwOS) in a subgroup of patients with mutation in KRAS
timeFrame: 6, 12 and 18 months
measure: Median overall survival (mOS) in a subgroup of patients with mutation in KRAS
timeFrame: up to 24 months
measure: Real-world overall survival (rwOS) in a subgroup of patients with mutation in STK11
timeFrame: 6, 12 and 18 months
measure: Median overall survival (mOS) in a subgroup of patients with mutation in STK11
timeFrame: up to 24 months
measure: Real-world treatment response of TDC, as judged by the treating physician
timeFrame: up to 24 months
measure: Duration of response (DoR)
timeFrame: up to 24 months
measure: Real-world progression-free survival (rwPFS)
timeFrame: up to 24 months
measure: Safety: Collection of Adverse Events (AE)
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Bad Homburg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Celle
country: Germany
facility: Research Site
city: Chemnitz
country: Germany
facility: Research Site
city: Georgsmarienhutte
country: Germany
facility: Research Site
city: Gera
country: Germany
facility: Research Site
city: Gostar
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Herne
country: Germany
facility: Research Site
city: Munnerstadt
country: Germany
facility: Research Site
city: Ravensburg
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Zwickau
country: Germany
facility: Research Site
Study officials:
References: