On September 15, 2021, the kinase inhibitor mobocertinib was granted accelerated approval by the U.S. Food and Drug Administration (FDA) for adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.1 The FDA simultaneously approved the Oncomine Dx Target Test as a companion diagnostic device to select patients for mobocertinib treatment.
Supporting Efficacy Data
Approval was based on findings in the international multicohort AP32788-15-101 study (ClinicalTrials.gov identifier NCT02716116), in which 114 patients received oral mobocertinib at 160 mg once daily until disease progression or intolerable toxicity.1 On blinded independent central review, objective responses (all partial) were observed in 32 patients (28%, 95% confidence interval [CI] = 20%–37%). The median response duration was 17.5 months (95% CI = 7.4–20.3 months), with response for at least 6 months reported in 59% of responders.
How It Is Used
Patients must be selected for treatment in the current indication based on the presence of EGFR exon 20 insertion mutations, as detected by an FDA-approved test.
The recommended mobocertinib dose is 160 mg once daily until disease progression or unacceptable toxicity.
Product labeling provides instructions on dosage modification, including dose reduction, for adverse reactions including QTc interval prolongation and torsades de pointes; interstitial lung disease/pneumonitis; decreased ejection fraction or heart failure; diarrhea; and intolerable or recurrent grade 2 reactions and grade 3 or 4 reactions. Product labeling provides instructions on concomitant use with strong or moderate CYP3A inhibitors (which may contribute to QTc prolongation) and strong or moderate CYP3A inducers.
Among 114 patients receiving mobocertinib in study AP32788-15-101, the most common adverse events of any grade (> 20%) were diarrhea (92%), rash (78%), stomatitis (46%), vomiting (40%), decreased appetite (39%), paronychia (39%), nausea (37%), musculoskeletal pain (34%), fatigue (29%), pruritus (24%), cough (24%), and decreased weight (21%). The most common grade 3 or 4 adverse events included diarrhea (22%) and stomatitis, nausea, dyspnea, and hypertension (4.4% each). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (15%), increased amylase (13%), and increased lipase (10%).
Serious adverse events occurred in 46% of patients (diarrhea, dyspnea, vomiting, pyrexia, acute kidney injury, nausea, pleural effusion, and cardiac failure in ≥ 2% each). Adverse events led to treatment discontinuation in 17% (diarrhea and nausea in ≥ 2% each). Fatal adverse events occurred in 1.8% of patients, including cardiac failure (0.9%) and pneumonitis (0.9%).
Mobocertinib has a boxed warning for QTc prolongation and torsades de pointes. It has warnings/precautions for interstitial lung disease/pneumonitis, cardiac toxicity, diarrhea, and embryofetal toxicity. Patients should be advised not to breastfeed. while receiving mobocertinib.
1. Exkivity (mobocertinib) capsules prescribing information, Takeda Pharmaceuticals, September 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215310s000lbl.pdf. Accessed October 4, 2021.