Summary: EGFR Exon20ins+ non-small cell lung cancer (NSCLC) is an extremely rare cancer, primarily affecting young adults and non-smokers. Its prognosis is worse than other EGFR mutations, and currently available EGFR-TKIs and chemotherapy offer limited benefit to these patients.
Recently, Takeda Pharmaceutical announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional approval to its innovative lung cancer drug Exkivity (mobocertinib) as a monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations who have progressed after platinum-based chemotherapy.
Previously, Exkivity received priority review and was granted Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation by the US Food and Drug Administration (FDA). It is the first and only approved oral therapy specifically targeting EGFR exon 20 insertion mutations.
This approval gives Exkivity an advantage over Rybrevant, an intravenous therapy awaiting approval in the UK. In May 2021, the Food and Drug Administration (FDA) approved Rybrevant for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring EGFR ex20ins mutations who have progressed after failure of platinum-based chemotherapy. Notably, Rybrevant was the first targeted therapy to receive regulatory approval for EGFR ex20ins-mutant NSCLC.
In September 2021, the US FDA approved Exkivity (mobocertinib). FDA approval of Exkivity was based on results from an international, multicenter phase 1/2 clinical trial (NCT02716116). This trial included 114 patients with EGFR ex20ins-mutant NSCLC who had previously received platinum-based chemotherapy and received oral mobocertinib (160 mg once daily).
The study results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting: According to the assessment of the Independent Review Committee (IRC), the objective response rate (ORR) was 28%, the median duration of response (DOR) was 17.5 months, the disease control rate (DCR) was 78%, the median overall survival (OS) was 24 months, the 1-year survival rate was 70%, and the median progression-free survival (PFS) was 7.3 months. Treatment response was observed in NSCLC patients with various EGFR ex20ins mutations. The safety profile observed in this study was manageable and consistent with previous results.
It is understood that Exkivitiy and Rybrevant are the only drugs specifically designed for EGFR exon 20. Other EGFR inhibitors, such as AstraZeneca's Tagrisso, have shown poor performance against this subtype.
