TARGET-EU: Nivolumab plus ipilimumab with chemotherapy versus pembrolizumab with chemotherapy in patients with non-oncogenic metastatic non-small-cell lung cancer with <1% PD- L1 tumour expression

Study identification

• EU PAS number:
  EUPAS1000000987
• Study ID:
  1000000987
• Official title and acronym:
  TARGET-EU: Nivolumab plus ipilimumab with chemotherapy versus pembrolizumab with chemotherapy in patients with non-oncogenic metastatic non-small-cell lung cancer with <1% PD- L1 tumour expression
• DARWIN EU® study:
  No
• Study countries:
  Netherlands
• Study description:
  This case study is part of the broader TARGET-EU project (EUPAS1000000539) which aims to advance the use of real-world data through the application of target trial emulation and estimand methodologies. ; ; Background: Indirect comparisons of clinical trial data suggest that in patients with non-oncogenic metastatic NSCLC and with <1% PD-L1 tumour expression, first line nivolumab plus ipilimumab with chemotherapy is associated with better survival compared to pembrolizumab with chemotherapy. However, head-to-head comparative trials are lacking. This study is a comparative effectiveness assessment of overall survival from these two therapeutic options in the Dutch routine care clinical setting.; ; Objective: The objective of this study is to compare overall survival of nivolumab plus ipilimumab with chemotherapy versus pembrolizumab with chemotherapy in patients with non-oncogenic metastatic NSCLC and <1% PD-L1 tumour expression; ; Methods: This study will be conducted using real-world data from the Dutch national cancer registry (IKNL) and include all patients who started either treatment between 1-1-2022 and 31-12-2024. The primary estimand will be estimated using an inversed probability weighted Cox proportional hazard regression with treatment group as a single covariate and using inverse probability of treatment (IPTW) weighting based on propensity score estimation. The secondary estimand will be estimated using an accelerated failure time model to estimate restricted mean survival time at 1, 2 and 3 years after start of treatment using a Weibull distribution. A sensitivity analysis will be conducted to assess the potential impact of unmeasured confounding from corticosteroids use at baseline.
• Study status:
  Planned

Research institutions and networks

Institutions

Electronic Health Records (EHR) Research Group, London School of Hygiene & Tropical Medicine (LSHTM)

United Kingdom

Division of Pharmacoepidemiology & Clinical Pharmacology (PECP), Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University

Netherlands

Clinical Pharmacology, Vall d'Hebron Institut de Recerca (VHIR)

Spain

University Medical Center Utrecht (UMCU)

Netherlands

Teamit Institute

Spain

Sint Antonius Hospital, Utrecht/Nieuwegein, the Netherlands

Clinical Data Science (IKNL), Netherlands Comprehensive Cancer Organisation

Netherlands

Networks

Vaccine monitoring Collaboration for Europe (VAC4EU)

Belgium

Denmark

Finland

France

Germany

Italy

Netherlands

Norway

Spain

United Kingdom

EU Pharmacoepidemiology and Pharmacovigilance (PE&PV) Research Network

Netherlands

Study timelines

Date when funding contract was signed

Planned:19/09/2024

Study start date

Planned:09/03/2026

Date of final study report

Planned:10/07/2026

Sources of funding

EMA

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable