Non-squamous Metastatic Non-Small-Cell Lung Carcinoma
Conditions
Keywords
NSCLC,, mNSCLC,, KRAS,, STK11,, KEAP1,, TP53,, POSEIDON,, Tremelimumab,, Durvalumab
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.
Interventions
None listed
Sponsors
AstraZeneca
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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\* * Mixed histology NSCLC with both adenocarcinoma and squamous cell carcinoma components (adenosquamous carcinoma or any mixed NSQ- squamous tumor), regardless of the predominant component * determined by investigator as likely to influence the prognosis or management of mNSCLC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Two-year real-world overall survival (rwOS) rate of patients with NSQ mNSCLC in the total study population | Time from patient's index date until death by any cause, up to 24 months | 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. |
| Two-year real-world overall survival (rwOS) rate of patients with NSQ mNSCLC in patients with mutations in KRAS | Time from patient's index date until death by any cause, up to 24 months | 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. |
| Two-year real-world overall survival (rwOS) rate of patients with NSQ mNSCLC in patients with mutations in STK11 | Time from patient's index date until death by any cause, up to 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Real-world treatment response of TDC, as judged by the treating physician | up to 24 months | 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. |
| Duration of response (DoR) | up to 24 months | 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. |
| Real-world progression-free survival (rwPFS) | up to 24 months | 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. |
| Safety: Collection of Adverse Events (AE) | up to 24 months | Safety evaluated based on type of Adverse Event (AE), intensity, causal relationship to treatment, duration, handling, outcome, and seriousness. |
| Real-world overall survival (rwOS) in the total study population | 6, 12 and 18 months | rwOS rate (percentage of patients being alive derived by Kaplan-Meier methods) at 6, 12 and 18 months |
| Median overall survival (mOS) in the total study population | up to 24 months | 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. |
| Median overall survival (mOS) in a subgroup of patients with mutation in KRAS | up to 24 months | 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. |
| Real-world overall survival (rwOS) in a subgroup of patients with mutation in KRAS | 6, 12 and 18 months | rwOS rate (percentage of patients being alive derived by Kaplan-Meier methods) at 6, 12 and 18 months |
| Real-world overall survival (rwOS) in a subgroup of patients with mutation in STK11 | 6, 12 and 18 months | rwOS rate (percentage of patients being alive derived by Kaplan-Meier methods) at 6, 12 and 18 months |
| Median overall survival (mOS) in a subgroup of patients with mutation in STK11 | up to 24 months | 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. |
Countries
Germany
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed