Mobocertinib Approved in EGFR Exon 20 Insertion+ NSCLC

On September 15, FDA granted approval to mobocertinib, a first-in-class oral tyrosine kinase inhibitor (TKI) for locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. The therapy, to be sold as Exkivity by Takeda, is approved for adult patients whose disease has progressed on platinum-based chemotherapy.

Mutations will be detected with Thermo Fisher Scientific’s Oncomine Dx Target Test, which was simultaneously approved as a next-generation sequencing companion diagnostic.

NSCLC accounts for 85% of the 1.8 million new cases of lung cancer diagnosed each year worldwide, as estimated by the World Health Organization. Patients with EGFR Exon20 insertion+ NSCLC make up approximately 1% to 2% of patients with NSCLC and have lacked treatment options.

Approval of mobocertinib is based on phase 1/2 data presented during the 2021 meeting of the American Society of Clinical Oncology, which showed an overall response rate (ORR) of 28% and a median duration of response (DoR) of 17.5 months. Mobocertinib showed a median overall survival of 24 months in patients with platinum-based chemotherapy.

“The approval of Exkivity introduces a new and effective treatment option for patients with EGFR Exon20 insertion+ NSCLC, fulfilling an urgent need for this difficult-to-treat cancer,” Teresa Bitetti, president, Global Oncology Business Unit, Takeda, said in a statement. “Exkivity is the first and only oral therapy specifically designed to target EGFR Exon20 insertions, and we are particularly encouraged by the duration of the responses observed with a median of approximately 1.5 years. This approval milestone reinforces our commitment to meeting the needs of underserved patient populations within the oncology community.”

The review took place under Project Orbis, an initiative of the FDA Oncology Center of Excellence, which allows manufacturers to simultaneously have oncology products reviews among international partners.

“EGFR Exon20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi A. Jänne, MD, PhD, Dana Farber Cancer Institute. “The approval of Exkivity (mobocertinib) marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses.”

Common adverse reactions were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.