1510TiP - Efficacy study of osimertinib in treatment-naïve patients with EGFR mutant non-small cell lung cancer (NSCLC) according to TP53 mutational status (TEMPLE-2/NCT05785208)

Background

Osimertinib (Osi) is the standard first-line therapy for patients (pts) with advanced NSCLC harbouring common Epidermal Growth Factor Receptor (EGFR) mutations. Not all pts achieve durable benefit during treatment developing early resistance. Increasing evidence suggest a potential implication of Tumor Protein 53 (TP53) in the biological mechanisms underlying resistance to Tyrosine Kinase Inhibitors (TKIs). Our previous study on EGFR+ advanced NSCLC pts receiving first-line gefitinib showed that additional coexisting mutations (ACM) significantly decrease the efficacy of TKIs and, among them, TP53 mutations were exclusively documented in poor/intermediate responders than in good, supporting the potential role of this gene in influencing the response to anti-EGFR agents. These data highlight the need of applying more informative and comprehensive techniques for molecular analysis and treatment monitoring to implement the prediction of the awaited TKIs efficacy, identify pts who will not benefit from TKIs and ideally build for them a rational polytherapy strategy.

Trial design

TEMPLE-2 (NCT05785208) is a prospective, biomarker-driven, multicenter, open-label, clinical trial to evaluate the efficacy of Osi in treatment-nai¨ve patients affected by EGFR+ NSCLC according to TP53 mutational status. Inclusion criteria are: age >18 years, histologically confirmed diagnosis of EGFR+ NSCLC, available tumor tissue sample. The study consists of a screening phase to assess eligibility; a treatment phase in which pts will receive Osi at standard dose of 80 mg daily and a follow-up phase to monitor survival status and subsequent therapies. A population of 122 enrolled pts is expected, 61 TP51-wilde type and 61 TP-53 mutant. Primary endpoint is Progression Free Survival (PFS) according to TP53 mutational status; key secondary endpoints are Overall Survival (OS), Overall Response Rate (ORR), Disease Control Rate (DCR), Time to Central Nervous System (CNS) Progression, CNS ORR and Safety. Concomitant genomic alterations will be evaluated in tissue and blood at baseline and progression; ctDNA will be monitored during treatment. Enrollment is ongoing.

Clinical trial identification

NCT05785208.

Editorial acknowledgement

Legal entity responsible for the study

Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Funding

AstraZeneca.

Disclosure

E. Bria: Financial Interests, Personal, Advisory Board: AZ, Roche, BMS, MSD, Eli Lilly, Amgen, Pfizer, Novartis; Financial Interests, Personal, Invited Speaker: AZ, Roche, BMS, MSD, Eli Lilly, Pfizer, Novartis; Financial Interests, Institutional, Research Grant: AZ, Roche. All other authors have declared no conflicts of interest.