FDA Approves First Oral Drug for NSCLC With EGFR Exon20 Insertion

Nick Mulcahy

September 16, 2021

The US Food and Drug Administration (FDA) has granted an accelerated approval to mobocertinib (Exkivity, Takeda) for the treatment of patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR exon20 insertion mutation detected on an FDA-approved test.

Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.

"EGFR Exon20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs," said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, Massachusetts, in a press statement from the maker, Takeda.

"The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses," Jänne added.

According to the company, EGFR Exon20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.

The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.

Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.

Median overall survival was 24 months and median progression-free survival was 7.3 months.

The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific's Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon20 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 Exon20 insertions," according to the company.

Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The most common adverse reactions (> 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.

The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

"Patients with EGFR Exon20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates," said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.

The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.

The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.

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