FDA Grants Accelerated Approval to Mobocertinib for Patients With Metastatic NSCLC and EGFR Exon 20 Insertion Mutations

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On September 15, the U.S. Food and Drug Administration (FDA) granted accelerated approval to mobocertinib (Exkivity) for adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) and EGFR exon 20 insertion mutations (as detected by an FDA-approved test) whose disease has progressed on or after platinum-based chemotherapy. Mobocertinib is a small-molecule tyrosine kinase inhibitor designed to selectively target EGFR and HER2 exon 20 insertion mutations.

The FDA also approved the Oncomine Dx Target Test as a companion diagnostic device to select patients with the previously mentioned mutations for mobocertinib treatment.

Study 101

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

The main efficacy outcome measures were overall response rate according to Response Evaluation Criteria in Solid Tumors version 1.1 as evaluated by blinded independent central review and response duration. The overall response rate was 28% (95% confidence interval [CI] = 20%–37%), with a median response duration of 17.5 months (95% CI = 7.4–20.3 months).

The most common adverse reactions (> 20%) 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, and warnings for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

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

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

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

This review also used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application approximately 6 weeks ahead of the FDA goal date. This application was granted Priority Review, Breakthrough Therapy designation, and orphan drug designation.