General Information

Exkivity (mobocertinib) is a kinase inhibitor specifically designed to selectively target epidermal growth factor receptor (EGFR) Exon20 insertion mutations.

Exkivity is specifically indicated 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 mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

Exkivity is supplied as a capsule for oral administration. The recommended dose is 160 mg orally once daily until disease progression or unacceptable toxicity. Take Exkivity with or without food at the same time each day. Swallow Exkivity capsules whole. Do not open, chew or dissolve the contents of the capsules. If a dose is missed by more than 6 hours, skip the dose and take the next dose the following day at its regularly scheduled time. If a dose is vomited, do not take an additional dose. Take the next dose as prescribed the following day.

Mechanism of Action

Exkivity (mobocertinib) is a kinase inhibitor specifically designed to selectively target epidermal growth factor receptor (EGFR) Exon20 insertion mutations at lower concentrations than wild type (WT) EGFR. Two pharmacologically-active metabolites (AP32960 and AP32914) with similar inhibitory profiles to mobocertinib have been identified in the plasma after oral administration of mobocertinib. In vitro, mobocertinib also inhibited the activity of other EGFR family members (HER2 and HER4) and one additional kinase (BLK) at clinically relevant concentrations (IC50 values <2 nM).

Side Effects

Adverse effects associated with the use of Exkivity may include, but are not limited to, the following:

• diarrhea
• rash
• nausea
• stomatitis
• vomiting
• decreased appetite
• paronychia
• fatigue
• dry skin
• Grade 3 or 4 laboratory abnormalities including decreased lymphocytes, increased amylase, increased lipase, decreased potassium, decreased hemoglobin, increased creatinine, and decreased magnesium

The Exkivity drug label comes with the following Black Box Warning: 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.

Clinical Trial Results

This indication is approved under Accelerated Approval based on overall response rate (ORR) and DoR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA approval is based on results from the platinum-pretreated population in the Phase 1/2 trial of EXKIVITY, which consisted of 114 patients with EGFR Exon20 insertion+ NSCLC who received prior platinum-based therapy and were treated at the 160 mg dose. Data demonstrated a confirmed ORR of 28% per independent review committee (IRC) (35% per investigator) as well as a median DoR 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.