FDA Grants Accelerated Approval to Mobocertinib for Metastatic Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Variants

September 16, 2021

On September 15, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to mobocertinib (Exkivity™) for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion variants, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

FDA Grants Accelerated Approval to Mobocertinib for Metastatic Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Variants

FDA also approved the Oncomine Dx Target Test as a companion diagnostic device to identify patients with the variants for mobocertinib treatment.

Approval was based on an international, nonrandomized, open-label, multicohort clinical trial (study 101, NCT02716116) which included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion variants. Efficacy was evaluated in 114 patients whose disease had progressed on or after platinum-based chemotherapy. Patients received mobocertinib 160 mg orally daily until they experienced disease progression or intolerable toxicity.

The main efficacy outcome measures were overall response rate (ORR) according to response evaluation criteria in solid tumors 1.1, as evaluated by blinded independent central review, and response duration. The ORR was 28% (95% CI = 20%, 37%) with a median response duration of 17.5 months (95% CI = 7.4, 20.3).

The most common adverse reactions reported in 20% or more of patients receiving mobocertinib were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. Product labeling includes a boxed warning for QTc prolongation and Torsades de Pointes, as well as warnings for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

The recommended mobocertinib dose is 160 mg orally once daily until the patient develops disease progression or unacceptable toxicity.

View the full prescribing information for mobocertinib.

The indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for the indication may be contingent on verification and description of clinical benefit in a confirmatory trial.

The review was conducted under Project Orbis, an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, and United Kingdom’s Medicines and Healthcare Products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application approximately six weeks ahead of FDA’s goal date.

FDA granted application priority review, breakthrough therapy designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for IndustryꟷExpedited Programs for Serious ConditionsꟷDrugs and Biologics. 

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088. 

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. 


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