• A new drug, Exkivity (mobocertinib), has been approved by the U.S. Food and Drug Administration (FDA) for treating advanced non-small cell lung cancer (NSCLC) with specific genetic changes.
• A clinical trial found that the drug was safe, effective, and improved median overall survival rates to 24 months.
• This drug is the first to target a specific genetic mutation found in 1 percent to 2 percent of cases of NSCLC.

A new medication to treat non-small cell lung cancer has been approved by the U.S. Food and Drug Administration. Pharmaceutical company Takeda’s Exkivity (mobocertinib) is the first drug developed to work against a specific mutation found in cancer cells in 1 percent to 2 percent of NSCLC cases. This mutation is called an epidermal growth factor receptor (EGFR) exon 20 insertion. In general, EGFR mutations are more prevalent in people who have never smoked, people with Eastern Asian ethnicity, and those with adenocarcinomas.

The FDA has approved Exkivity to treat people with locally advanced or metastatic NSCLC in which cancer cells have an EGFR exon 20 insertion. This means that a piece of DNA from another gene was inserted into the gene for EGFR, which controls cell growth and division. When this gene is mutated in lung cancer, it causes cells to grow and divide uncontrollably, causing a tumor to form. Exkivity works by blocking the mutated EGFR protein so that it cannot tell cells to grow and divide anymore.

An oral therapy, Exkivity was studied in a phase 1/2 clinical trial of 114 participants living with NSCLC with an EGFR exon 20 insertion. The participants all had all been previously treated with platinum-based chemotherapy. Each participant received a daily 160 milligram dose of Exkivity for the length of the study. The treatment was found to be safe and effective, with a median overall survival rate of 24 months. These results were presented last May at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

The most common side effects participants experienced during the study include:

• Fatigue
• Diarrhea
• Rash
• Nausea
• Vomiting
• Loss of appetite
• Musculoskeletal pain
• Inflammation and infection around the nails (known as paronychia)
• Dry skin

Some more serious cases of nausea and diarrhea which required medical intervention were noted during the study.

Some doctors and researchers have expressed optimism about Exkivity’s treatment potential. In a Takeda press release, Marcia Horn from the International Cancer Advocacy Network said, “Patients with EGFR exon 20 insertion-positive NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed, but also lacking targeted treatment options that can improve response rates.”

In the same press release, Pasi Jänne of Dana Farber Cancer Institute — who was involved in the clinical trials — said, “EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs (tyrosine kinase inhibitors),”

In addition to Exkivity, the FDA also recently approved a genetic test to look for EGFR exon 20 insertions in people with NSCLC. Thermo Fisher Scientific developed its Oncomine Dx Target Test, which sequences the DNA from a person’s NSCLC tumor to look for mutations. The test is more accurate than other methods used before, which detected less than 50 percent of EGFR exon 20 insertions. This testing, combined with Exkivity treatment, is providing hope for people with NSCLC with an EGFR exon 20 insertion.