FDA Grants Priority Review to Mobocertinib for EGFR Exon 20 Insertion+ Metastatic NSCLC


Based on response efficacy in a phase 1/2 trial, the FDA granted the selective oral tyrosine kinase inhibitor mobocertinib priority review for patients with pretreated metastatic non–small cell lung cancer harboring insertion mutations in EGFR exon 20.

A new drug application for the oral tyrosine kinase inhibitor (TKI) mobocertinib (TAK-788) was granted priority review by the FDA for the treatment of patients with metastatic non–small cell lung cancer (mNSCLC) and an EGFR exon 20 insertion mutation who have received prior platinum-based chemotherapy, according to Takeda Pharmaceutical Company Limited, the company responsible for developing the agent.

The investigational, first-in-class, small-molecule TKI selectively targets exon 20 insertion mutations in EGFR. Data supporting the NDA are primarily based on a phase 1/2 trial (NCT04535557), which demonstrates promising responses with the therapy in this subpopulation of patients.1

“Patients with EGFR exon 20 insertion[–positive] mNSCLC face considerable challenges, as current treatment options provide limited benefit, resulting in poor survival outcomes,” Christopher Arendt, head of the Oncology Therapeutic Area Unit at Takeda, said in a press release. “We are excited to be one step closer to offering mobocertinib as an effective oral therapy for NSCLC patients with EGFR exon 20 insertions that have received prior platinum-based chemotherapy and look forward to continuing conversations with regulatory agencies in the US and around the globe.”

Data from the supporting trial were previously presented at the 2020 World Conference on Lung Cancer Singapore in January 2021. The efficacy analysis included 114 patients who received prior platinum-based therapy and were treated as part of the dose-escalation and dose-expansion portions of the phase 1/2 trial. Patients were treated with mobocertinib at 160 mg once daily.

In patients who were previously treated with platinum-based chemotherapy, the confirmed objective response rate (ORR) per an independent review committee (IRC) was 26% (95% CI, 19%-35%), and 35% (95% CI, 26%-45%) by investigator assessment. The median progression-free survival (PFS) was 7.3 months via both IRC and investigator assessment. Median duration of response by IRC was 17.5 months (95% CI, 7.4-20.3).2,3 

“Results show mobocertinib demonstrated clinically meaningful responses and a noteworthy duration of response in patients with EGFR exon 20 insertion–positive metastatic NSCLC who received prior platinum-based therapy,” Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, said during a presentation of the results. “These data are promising and provide further evidence for mobocertinib as a potential oral treatment for patients with EGFR exon 20 insertion–mutant metastatic NSCLC, who are in critical need of targeted treatment options.”

The safety profile of mobocertinib was consistent with the known profiles of other EGFR TKIs. Treatment-related adverse events (TRAEs) occurring in at least 20% of patients previously treated with platinum chemotherapy included diarrhea (90%), rash (45%), paronychia (34%), nausea (32%), decreased appetite (32%), dry skin (30%), and vomiting (30%). TRAEs occurring in 5% or more of patients included diarrhea (21%). Discontinuations due to AEs occurred in 17% of patients, most commonly from diarrhea (4%) and nausea (4%).

Of note, responses in patients who were previously treated with TKIs were also presented at the meeting, showing a confirmed ORR of 23% (95% CI, 15%-33%) per IRC and 32% (95% CI, 23%-43%) by investigator assessment. The median PFS by IRC and investigator assessment was 7.3 months and 7.1 months, respectively.

The NDA is being reviewed under the accelerated approval program. Project Orbis, an initiative of the FDA Oncology Center of Excellence, which allows concurrent submission and review of products to international agencies, is conducting the review.

In April 2020, the agent also received a breakthrough therapy designation by the FDA for the indicated patient population.


1. Takeda Announces U.S. FDA Grants Priority Review for New Drug Application for Mobocertinib (TAK-788) as a Treatment for EGFR Exon20 Insertion+ Metastatic Non-Small Cell Lung Cancer. News release. Takeda. April 28, 2021. Accessed April 28, 2021. https://bit.ly/32Wi45e

2. Zhou C, Ramalingam S, Li B, et al. OA04.03 Mobocertinib in NSCLC with EGFR exon 20 insertions: results from EXCLAIM and pooled platinum-pretreated patient populations. J Thorac Oncol. 2021;16(suppl 16):S108. doi: 10.1016/j.jtho.2021.01.283

3. Takeda presents positive results for mobocertinib in patients with EGFR exon20 insertion+ mNSCLC who received prior platinum-based chemotherapy. News release. Takeda. January 28, 2021. Accessed April 28, 2021. https://bit.ly/36oWCHT

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