Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122)

Introduction: Pemetrexed-based immunochemotherapy represents an established standard of care as first line treatment for non-oncogenic driven metastatic non-small cell lung adenocarcinoma (NSCLC/ADC). However, retrospective analyses revealed better outcomes for pemetrexed-free regimens compared to pemetrexed-containing regimens in patients with thyroid transcription factor 1 (TTF-1) negative NSCLC/ADC. The multicenter, phase II, randomized, open label ANTELOPE trial evaluates whether atezolizumab, carboplatin and nab-paclitaxel is superior to pembrolizumab, cis-/carboplatin and pemetrexed in TTF-1 negative NSCLC/ADC. Methods: Eligible participants are >= 18 years of age, with histologically or cytologically confirmed, treatment-naive stage IV TTF-1 negative NSCLC/ADC without actionable genomic alterations or PD-L1-overexpression (TPS >= 50%) and will be randomized in a 1:1 fashion to pemetrexed-free (group A) vs. pemetrexed-based (group B) immunochemotherapy. The pr imary endpoint of this tr ial is overall survival (OS). Results: Enrollment will start in Q2 2023 at 30 sites in Germany with a planned inclusion of 136 participants. Conclusion: ANTELOPE will provide efficacy outcomes of the current standard-of-care for the specific subset of TTF-1 negative NSCLC/ADC in a head-to-head comparison of approved immunochemotherapy regimens.

Automated summary

Pemetrexed-free regimens may have better outcomes compared to pemetrexed-containing regimens in TTF-1 negative NSCLC/ADC patients. The ANTELOPE trial aims to compare atezolizumab, carboplatin, and nab-paclitaxel with pembrolizumab, cis-/carboplatin, and pemetrexed in this specific subset of patients.