The First Oral Drug for Lung Cancer with EGFR Exon 20 Mutations Received FDA Approval

For patients whose epidermal growth factor receptor (EGFR) has exon 20 insertion mutations and who have locally advanced or metastatic non-small cell lung cancer (NSCLC), the capsule-form drug mobocertinib (Exkivity, Takeda) received accelerated approval on September 15, 2021 from the FDA (US Food and Drug Administration).

The drug is approved for patients whose disease progressed during or after platinum -based chemotherapy and whose EGFR exon 20 insertion mutation was identified by an FDA-approved test — in other words, as second-line treatment.

EGFR Exon 20 Insertion Mutation

Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these exon 20 mutations, which are less common than other more prevalent EGFR mutations in lung cancer.

For EGFR exon 20 insertion mutations, mobocertinib is the 2nd drug to receive FDA approval. Previously, on May 21, 2021, the FDA approved Rybrevant, whose active ingredient is amivantamab-vmjw, for patients whose tumors carry EGFR exon 20 insertion mutations.

EGFR Exon20 insertion mutations account for approximately 1–2% of patients with NSCLC and are more common in Asian populations than in Western populations.

The Study Leading to FDA Approval of Mobocertinib

The new approval comes from a single-arm phase 1/2 clinical trial involving 114 patients. The primary endpoints the study aimed to measure were objective response rate and duration of response. All patients had previously received platinum-based chemotherapy, and the mobocertinib dose was 160 mg daily.

• According to an independent review committee, mobocertinib showed a confirmed objective response rate of 28% and a median response duration of 17.5 months.
• Median overall survival was 24 months, and progression-free survival was 7.3 months.

To determine eligibility for mobocertinib, the FDA approved the next-generation sequencing (NGS) test, Thermo Fisher Scientific's Oncomine Dx Target Test, which identifies patients with NSCLC and EGFR Exon20 insertions.

The NGS test, compared with a test detecting fewer than 50% of EGFR Exon20 insertions, polymerase chain reaction (PCR), is critical for these patients because it can provide more accurate diagnoses.

The most common (> 20%) side effects with mobocertinib were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia (infection around the nail), fatigue, dry skin and musculoskeletal pain.