T-DM1 and Osimertinib Combination Treatment to Target HER2 Bypass Track Resistance in EGFR Mutation Positive NSCLC

Summary

Participation Requirements

Description

This study is a multicenter single arm phase II study with a phase I run in to study the toxicity and efficacy of T-DM1 and osimertinib combination treatment in patients with EGFR mutated NSCLC and HER2 bypass track activation (HER2 immunohistochemistry (IHC) ?2+ and/or HER2 amplification) after pro...

This study is a multicenter single arm phase II study with a phase I run in to study the toxicity and efficacy of T-DM1 and osimertinib combination treatment in patients with EGFR mutated NSCLC and HER2 bypass track activation (HER2 immunohistochemistry (IHC) ?2+ and/or HER2 amplification) after progression on an EGFR TKI. In the phase I run in, study safety will be assessed in a classical 3+3 design. Because of potential for overlapping hematologic and non-hematologic adverse events (AE), the first 3 patients will receive a reduced dose of T-DM1 3.0 mg/kg IV every 3 weeks combined with osimertinib 80 mg once daily. Dose-limiting toxicity (DLT) is defined as a grade 3 AE toxicity according to CTC AE 4.03 that does not recover to grade ?2 before the next cycle of T-DM1. DLT's will be collected up to 6 weeks after treatment initiation (2 T-DM1 cycles). Dose escalation within patients is not allowed. If 1 patient develops a dose-limiting toxicity (DLT), 3 more will be included and treated with T-DM1 3.0 mg/kg. If ?2 of the 6 patients develop a DLT, further study of the combination will be halted. Otherwise, T-DM1 3.0 mg/kg IV every 3 weeks combined with osimertinib 80 mg once daily will be the maximum tolerated dose (MTD) to put forward in the phase II part of this study. If none of the first three patients develops a DLT, the T-DM1 dose will be escalated to the standard dose of 3.6 mg/kg. If ?1 patient experiences a DLT in 6 patients (3+3), T-DM1 3.6 mg/kg IV every 3 weeks and osimertinib 80 mg once daily will be the MTD. If ?2 patients develop a DLT, the T-DM1 will be lowered to 3.0 mg/kg and three more patients will be enrolled in this dose cohort. When ?1 of these patients develops a DLT, this will be the MTD.

Tracking Information