2022 World Conference on Lung Cancer (ePosters)-EP08.02-109. A Drug-Drug Interaction Study of Mobocertinib and Midazolam in Patients With Advanced Non-Small Cell Lung Cancer

EP08.02-109. A Drug-Drug Interaction Study of Mobocertinib and Midazolam in Patients With Advanced Non-Small Cell Lung Cancer

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A drug-drug interaction study was conducted to evaluate the impact of co-administering mobocertinib and midazolam in patients with advanced non-small cell lung cancer (NSCLC). The study included 26 patients who received at least one dose of the study drug. Among these patients, 13 were evaluated for pharmacokinetics (PK). <br /><br />The results showed that the absorption of midazolam was not significantly affected by the presence of mobocertinib when administered orally or intravenously. However, co-administration of mobocertinib resulted in a 32% decrease in the area under the plasma concentration-time curve (AUC) for oral midazolam and a 16% decrease in the AUC for intravenous midazolam.<br /><br />The safety analysis revealed that the most common treatment-related adverse events (TRAEs) observed with mobocertinib were diarrhea, nausea, decreased appetite, fatigue, and vomiting. Grade 3 TRAEs were primarily limited to diarrhea.<br /><br />In terms of clinical activity, three out of 26 patients were classified as responders, with two of them having EGFR exon 20 insertion mutations. However, all three patients had discontinued treatment before the study ended.<br /><br />The study concluded that co-administration of mobocertinib with CYP3A substrates, such as midazolam, may lead to a decrease in plasma concentrations of these substrates, potentially reducing their efficacy. Therefore, it is suggested to avoid concurrent use of mobocertinib with CYP3A substrates, including hormonal contraceptives, where even minimal concentration changes can result in therapeutic failures.<br /><br />Overall, the safety findings of mobocertinib in patients with advanced NSCLC were consistent with its known safety profile, with diarrhea being the only Grade 3 TRAE observed. Mobocertinib is approved for patients with EGFR exon 20 insertion-positive locally advanced or metastatic NSCLC who have previously received platinum-based chemotherapy.

Asset Subtitle

Michael J. Hanley

Meta Tag

Speaker Michael J. Hanley

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

Keywords

drug-drug interaction

mobocertinib

midazolam

non-small cell lung cancer

pharmacokinetics

absorption

plasma concentration-time curve

adverse events

clinical activity

CYP3A substrates