FDA Approval Summary: Mobocertinib for Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

Area of Science:

• Oncology
• Pharmacology
• Genetics

Background:

• Non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations represents a significant unmet medical need.
• Platinum-based chemotherapy is a standard treatment, but outcomes for patients with these specific mutations remain limited.
• Targeted therapies have revolutionized cancer treatment, but options for EGFR exon 20 insertion mutations have been scarce.

Purpose of the Study:

• To evaluate the efficacy and safety of mobocertinib in patients with advanced NSCLC and EGFR exon 20 insertion mutations.
• To support the accelerated approval of mobocertinib as a novel treatment option.

Main Methods:

• An international, non-randomized, multi-cohort clinical trial (Study AP32788-15-101) was conducted.
• The study included adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations.
• Patients had disease progression following platinum-based chemotherapy.

Main Results:

• Mobocertinib demonstrated an overall response rate of 28% (95% CI, 20%-37%) in 114 evaluable patients.
• The median duration of response was 17.5 months (95% CI, 7.4-20.3).
• Common adverse reactions included diarrhea, rash, nausea, and stomatitis. A Boxed Warning addresses QTc prolongation.

Conclusions:

• Mobocertinib is the first oral targeted therapy approved for advanced NSCLC with EGFR exon 20 insertion mutations.
• This approval provides a crucial new treatment option for a previously difficult-to-treat patient population.
• Continued monitoring for adverse events, including QTc prolongation, is essential.