Phase I Study of Repotrectinib and Osimertinib in NSCLC Patients
Phase I Clinical Study to Assess Safety and Efficacy of Repotrectinib Combined With Osimertinib in Patients With Advanced, Metastatic EGFR Mutant NSCLC (TOTEM).
Instituto Oncológico Dr Rosell
32 participants
Feb 11, 2022
INTERVENTIONAL
Conditions
Summary
This is a Phase I study of repotrectinib in combination with osimertinib in patients with advanced or metastatic EGFR mutant non small cell lung cancer (NSCLC). The study will be conducted in 2 parts, Part Ia and Part Ib, and its purpose will be to find the incidence of dose-limiting toxicities (DLTs) as defined by the primary safety and tolerability endpoint. The Phase Ia study will also determine the impact of repotrectinib on osimertinib pharmacokinetics (PK) and the maximum tolerated dose (MTD), if reached, of repotrectinib given in combination with osimertinib and the recommended Phase II dose (RP2D). Dose escalation will be conducted according to a 'Rolling-6' based study design with 3 dose levels for repotrectinib: 80 mg once a day (QD), 160 mg QD or 160 mf QD during 14 days followed by 160 mg twice a day (BID); in combination with 80 mg QD of osimertinib. A total of 6 patients will be enrolled in each dose level cohort. In addition, this Phase Ib study will test early drug activity (efficacy) of the proposed combination treatment in an expansion cohort at the RP2D.
Eligibility
Plain Language Summary
Simplified for easier understanding
This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.
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Interventions
Repotrectinib will be taken orally once daily with or without food Part A: Dose escalation phase, with 3 dose levels for repotrectinib: (1) 80 mg QD, (2) 160 mg QD and (3) 160 mg QD for 14 days followed by 160 mg BID; in combination with 80 mg QD of osimertinib Part B: at the RP2D for all patients in combination with osimertinib.
Osimertinib will be taken orally at 80 mg once daily with or without food. Part A: lead in dose in monotherapy at 80 mg QD during 14 days. In combination with repotrectinib afterwards. Depending on the safety and PK/ dose dependent interactions (DDIs) readout during the DLT assessment period, osimertinib dose may be adjusted. Part B: at the RP2D level in combination with repotrectinib
Locations(4)
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NCT04772235