2022 World Conference on Lung Cancer (ePosters)-EP08.02-011. Design of a Phase I Trial (TOTEM) to Test Repotrectinib in Combination with Osimertinib in Advanced, Metastatic EGFR-Mutant NSCLC

EP08.02-011. Design of a Phase I Trial (TOTEM) to Test Repotrectinib in Combination with Osimertinib in Advanced, Metastatic EGFR-Mutant NSCLC

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The TOTEM trial is a phase I study designed to test the safety and efficacy of repotrectinib in combination with osimertinib for patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring an EGFR mutation. Osimertinib is currently the standard first-line treatment for EGFR-mutant NSCLC, but resistance to the drug can develop through activation of other signaling pathways. Repotrectinib is a receptor TKI that inhibits various signaling pathways involved in resistance mechanisms.<br /><br />The trial aims to evaluate the safety and tolerability of repotrectinib at different doses in combination with osimertinib. The primary objectives include determining the dose-limiting toxicities and maximum tolerated dose of repotrectinib, as well as the recommended Phase II dose. The trial also aims to assess the effect of repotrectinib on the pharmacokinetics of osimertinib and vice versa. Additionally, the trial will evaluate the preliminary activity and efficacy of the combination therapy in terms of objective response rate, duration of response, clinical benefit rate, progression-free survival, and overall survival. Pharmacodynamic effects and potential biomarkers predictive of response will be assessed using tumor biopsy and blood samples.<br /><br />The trial is a single arm, multicenter study being conducted in four hospitals in Spain. The study has already been initiated, and recruitment is expected to be completed by March 2023. The trial is currently enrolling patients who have advanced or metastatic EGFR-mutant NSCLC and have progressed on osimertinib. As of now, six out of the expected 38 patients have been enrolled in the trial.<br /><br />Overall, the TOTEM trial aims to determine the safety, tolerability, and efficacy of combining repotrectinib with osimertinib in patients with EGFR-mutant NSCLC. The trial will provide valuable information on the potential benefits of this combination therapy for patients with advanced or metastatic NSCLC.

Asset Subtitle

Andrés Aguilar

Meta Tag

Speaker Andrés Aguilar

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

TOTEM trial

phase I study

repotrectinib

osimertinib

non-small cell lung cancer

NSCLC

EGFR mutation

combination therapy

dose-limiting toxicities

maximum tolerated dose