# A phase 2 study of mobocertinib as first-line treatment in Japanese patients with non-small cell lung cancer harboring EGFR exon 20 insertion mutations

## TL;DR

A phase 2 study found that mobocertinib had limited effectiveness in treating Japanese patients with a specific type of lung cancer caused by EGFR exon 20 insertion mutations.

## Contribution

This study evaluates mobocertinib's efficacy as a first-line treatment for EGFR exon 20 insertion-mutated non-small cell lung cancer in Japanese patients.

## Key findings

- The objective response rate was 28.6% in an interim analysis of 14 patients.
- The full analysis showed an objective response rate of 18.2% across 33 patients.
- Common side effects included diarrhea, paronychia, stomatitis, and nausea.

## Abstract

Mobocertinib is a novel, synthetic, orally administered tyrosine kinase inhibitor that inhibits many activated forms of epidermal growth factor receptor (EGFR), including those containing exon 20 insertion (ex20ins) mutations. This study aimed to assess the efficacy of mobocertinib in Japanese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR ex20ins mutations.

This was a phase 2, open-label study. Patients with NSCLC harboring EGFR ex20ins mutations who had not had previous systemic treatment received mobocertinib 160 mg once daily. The primary endpoint was the confirmed objective response rate. A planned interim analysis was completed for the first 14 patients with a centrally confirmed EGFR ex20ins mutation, with enrollment stopped if the number of patients with an objective response was five or fewer.

In total, 33 patients were enrolled into the study (63.6% women; median age: 66 years). At the interim analysis, the objective response rate evaluated by a central independent review committee was 28.6% (4/14, 90% confidence interval: 10.4–54.0); therefore, enrollment was stopped for futility. In the full analysis set, the objective response rate was 18.2% (6/33, 95% confidence interval: 7.0–35.5); of the six responders, one patient (3.0%) had a complete response and five patients (15.2%) had partial responses. The most common treatment-related adverse events were diarrhea, paronychia, stomatitis, and nausea.

Although study enrollment was terminated early owing to futility, our results showed modest activity of mobocertinib in Japanese patients with NSCLC with EGFR ex20ins mutations with no additional safety concerns.

The online version contains supplementary material available at 10.1007/s10147-024-02588-y.