On July 12, China's CDE official website announced that Takeda's new oral small molecule drug mobocertinib capsule has been formally accepted by the China Food and Drug Administration. It is the first domestic application for EGFR exon 20 (Exon20) insertion mutation NSCLC. Treatment, and the product’s marketing application was also included in the priority review by CDE. On May 21st, Johnson & Johnson's EGFR/cMet dual antibody Rybrevant (amivantamab-vmjw) has been approved by the FDA for accelerated marketing by virtue of a single-arm trial of 81 patients in Phase I, becoming the first drug approved by the FDA for this type of mutation.

According to the entry priority review record, the indications for this application for marketing are: treatment of locally advanced or metastatic non-small cell lung cancer that has previously received chemotherapy and carries epidermal growth factor receptor (EGFR) exon 20 (Exon20) insertion mutations ( NSCLC) adult patients.

EGFR mutations are common gene mutations in patients with non-small cell lung cancer, accounting for about 10% to 15%. In Asian populations, this value is about 40% to 50%. EGFR exon 20 insertion mutations account for approximately 9% of all EGFR-mutant non-small cell lung cancer patients. Patients with non-small cell lung cancer with EGFR exon 20 insertion mutations are usually insensitive to EGFR-TKI treatment, and have a worse prognosis than patients with more common EGFR mutations (exon 19 deletion/L858R substitution). At present, the standard treatment for such patients is conventional cytotoxic chemotherapy.

Mobocertinib is a next-generation small molecule tyrosine kinase inhibitor (TKI), specifically designed to selectively inhibit epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) exon 20 mutations. It was awarded a breakthrough therapy designation by the FDA in April 2020 for the treatment of patients with EGFR Exon20 insertion mutation NSCLC who had disease progression during or after platinum-containing chemotherapy. On April 27, mobocertinib's marketing application for this indication was granted priority review by the FDA. In October last year, mobocertinib also received the CDE breakthrough therapy designation.

Data from a phase I/II clinical trial (NCT0271611) proved the efficacy and safety of mobocertinib. A total of 114 patients with NSCLC who had previously received platinum-based chemotherapy and had EGFR Exon20 insertion mutations were included in the result analysis. The independent review committee assessed that the objective response rate (ORR) of patients who received mobocertinib (160 mg) once a day was 28%. The duration of response (mDoR) was 17.5 months, the median progression-free survival (mPFS) was 7.3 months, and the disease control rate was 78%.

The safety of Mobocertinib is controllable. The most common treatment-related adverse events (TRAEs) include diarrhea (90%), rash (45%), paronychia (34%), nausea (32%), and decreased appetite (32%) , Dry skin (30%) and vomiting (30%). TRAEs of grade 3 and above (≥5%) were diarrhea (21%). Nineteen patients (17%) discontinued the drug due to AEs. The most common AEs leading to discontinuation were diarrhea (4%) and nausea (4%).