The Food and Drug Administration (FDA) has granted accelerated approval to Exkivity (mobocertinib) for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.
Exkivity is a first-in-class, oral tyrosine kinase inhibitor designed to selectively target EGFR exon 20 insertion mutations at lower concentrations than wild type EGFR. The approval was based on data from a multicenter, open-label phase 1/2 trial (ClinicalTrials.gov Identifier: NCT02716116), which assessed the efficacy and safety of Exkivity 160mg once daily in 114 adults with EGFR Exon20 insertion-positive locally advanced or metastatic NSCLC whose disease progressed on or after platinum-based chemotherapy.
An independent review committee found an overall response rate of 28% (n=32; 95% CI, 20%-37%), median duration of response (DOR) of 17.5 months (95% CI, 7.4-20.3), and 59% of patients had a DOR lasting at least 6 months. The median overall survival and progression-free survival were 24 and 7.3 months.
According to the investigator assessment, the overall response rate was 35% (95% CI, 26%-45%), with a median DOR of 11.2 months, and 63% of patients had a DOR lasting at least 6 months.
As for safety, Exkivity carries a Boxed Warning for life-threatening QTc prolongation, including Torsades de Pointes. Health care providers are required to monitor QTc and electrolytes at baseline and periodically during treatment.
The most common adverse reactions (incidence greater than or equal to 20%) are diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.
“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 from the 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.”
The FDA also approved Thermo Fisher Scientific’s Oncomine Dx Target Test as an NGS companion diagnostic to identify NSCLC patients with EGFR exon 20 insertions for Exkivity.
Exkivity will be available as 40mg capsules in 90- and 120-count bottles.
- Takeda’s Exkivity™ (mobocertinib) approved by US FDA as the first oral therapy specifically designed for patients with EGFR exon20 insertion+ NSCLC. News release. Takeda Pharmaceutical Company Limited. September 15, 2021. Accessed September 16, 2021. https://www.businesswire.com/news/home/20210915006101/en/Takeda%E2%80%99s-EXKIVITY%E2%84%A2-mobocertinib-Approved-by-U.S.-FDA-as-the-First-Oral-Therapy-Specifically-Designed-for-Patients-with-EGFR-Exon20-Insertion-NSCLC.
Exkivity. Package insert. Takeda Pharmaceutical Company Limited; 2021. Accessed September 16, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215310s000lbl.pdf