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Exkivity approved by U.S. FDA as the first oral therapy specifically designed for patients with EGFR exon 20 insertion mutation non-small cell lung cancer

The U.S. Food and Drug Administration ( FDA ) has approved Exkivity ( Mobocertinib ) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer ( NSCLC ) with epidermal growth factor receptor ( EGFR ) exon 20 insertion ( ex20-ins ) mutations as detected by an FDA-approved test, whose disease has progressed on or after Platinum-based chemotherapy.

Exkivity, which was granted priority review and received Breakthrough Therapy Designation, Fast Track Designation and Orphan Drug Designation from the FDA, is the first and only approved oral therapy specifically designed to target EGFR exon 20 insertion mutations.
This indication is approved under Accelerated Approval based on overall response rate ( ORR ) and duration of response ( DoR ).
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA simultaneously has approved Thermo Fisher Scientific’s Oncomine Dx Target Test as an Next Generation Sequencing ( NGS ) companion diagnostic for Exkivity to identify NSCLC patients with EGFR exon 20 insertions. NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction ( PCR ) testing, which detects less than 50% of EGFR exon 20 insertions.

The FDA approval is based on results from the Platinum-pretreated population in the phase 1/2 trial of Mobocertinib, which consisted of 114 patients with EGFR exon 20 insertion+ non-small cell lung cancer who received prior Platinum-based therapy and were treated at the 160 mg dose.
Results were presented at the 2021 American Society of Clinical Oncology ( ASCO ) Annual Meeting from the phase 1/2 trial and have demonstrated a confirmed overall survival rate of 28% per independent review committee ( IRC ) ( 35% per investigator ) as well as a median duration of response of 17.5 months per IRC, a median overall survival ( OS ) of 24 months and a median progression-free survival ( PFS ) of 7.3 months per IRC.

The most common adverse reactions ( more than 20% ) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.

Mobocertinib is a first-in-class, oral tyrosine kinase inhibitor ( TKI ) specifically designed to selectively target epidermal growth factor receptor exon 20 insertion mutations.

Non-small cell lung cancer is the most common form of lung cancer, accounting for approximately 85% of the estimated 2.2 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization ( WHO ).
Patients with EGFR exon 20 insertion+ non-small cell lung cancer make up approximately 1-2% of patients with NSCLC, and the disease is more common in Asian populations compared to Western populations.
This disease carries a worse prognosis than other EGFR mutations, as EGFR TKIs, which do not specifically target EGFR exon 20 insertions, and chemotherapy provide limited benefit for these patients.

Exkivity can cause life-threatening heart rate-corrected QT ( QTc ) prolongation, including Torsades de Pointes, which can be fatal, and requires monitoring of QTc and electrolytes at baseline and periodically during treatment.
Increase monitoring frequency in patients with risk factors for QTc prolongation.
Avoid use of concomitant drugs which are known to prolong the QTc interval and use of strong or moderate CYP3A inhibitors with Exkivity, which may further prolong the QTc.
Withhold, reduce the dose, or permanently discontinue Exkivity based on the severity of QTc prolongation. ( Xagena )

Source: Takeda, 2021