Mobocertinib Receives FDA Approval for Previously Treated NSCLC With EGFR Exon 20 Insertion Mutations


The FDA granted approval to the first oral therapy for advanced or metastatic non–small cell lung cancer harboring EGFR exon 20 insertion mutations, mobocertinib.

The FDA has granted approval to a new drug application (NDA) for mobocertinib (Exkivity; TAK-788) as a treatment for patients with locally advanced or metastatic non–small cell lung cancer (mNSCLC) and EGFR exon 20 insertion mutations who have received prior platinum-based chemotherapy, according to Takeda Pharmaceutical Company Limited, the company responsible for developing the agent.1

EGFR exon 20 insertion mutations will require confirmation by an FDA-approved test. The FDA also granted premarket approval to Thermo Fisher Scientific’s Oncomine Dx Target Test as a companion diagnostic for identifying patients with EGFR exon 20 insertion mutation–positive NSCLC who may be candidates for mobocertinib.2

The NDA was supported by data from a phase 1/2 trial (NCT04535557) in which the investigational, first-in-class, selective small-molecule tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertion mutations demonstrated promising responses in the indicated patient population.

“The approval of Exkivity introduces a new and effective treatment option for patients with EGFR Exon 20 insertion[-positive] NSCLC, fulfilling an urgent need for this difficult-to-treat cancer,” Teresa Bitetti, president of Global Oncology Business Unit at Takeda, said in a press release. “Exkivity is the first and only oral therapy specifically designed to target EGFR Exon 20 insertions, and we are particularly encouraged by the duration of the responses observed with a median of approximately 1.5 years. This approval milestone reinforces our commitment to meeting the needs of underserved patient populations within the oncology community.”

Results from the trial were previously reported at the 2021 American Society of Clinical Oncology Annual Meeting in June 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 trial.

The primary end point for the study was confirmed objective response rate (ORR), as assessed by independent review committee (IRC), while secondary end points included safety, tolerability, and efficacy. In the platinum-pretreated population, the median age was 60 years (range, 27-84), 66% of patients were female, and 60% were of Asian descent.

The confirmed overall response rate (ORR) by independent review committee (IRC) assessment was 28% (95% CI, 20%-37%); all responses were partial responses (PRs). By investigator assessment, the confirmed ORR was 35% (95% CI, 26%-45%); the complete response (CR) rate was less than 1%, and the PR rate was 34%.

The median duration of response (DOR) was 17.5 months (95% CI, 7.4-20.3) by IRC and 11.2 months (95% CI, 5.6–not evaluable [NE]) by investigator assessment. The confirmed disease control rate (DCR) was 78% (95% CI, 69%-85%) by IRC and investigator assessment.

The median overall survival was 24.0 months (95% CI, 14.6-28.8), and the median progression-free survival was 7.3 months (95% CI, 5.5-9.2).

The safety profile of mobocertinib was consistent with the known profiles of other EGFR TKIs. Regarding safety in the platinum-pretreated patient cohort, all patients (100%) reported any-grade adverse effects (AEs), and 99% of patients reported any-grade treatment-related AEs (TRAEs). Of these, any grade 3 or greater AEs were observed in 69% of patients and any grade 3 or greater TRAEs were observed in 47% of patients.

EGFR Exon2 0 insertion[-positive] NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” Pasi A. Jänne, MD, PhD, of Dana Farber Cancer Institute, said in a statement. “The approval of Exkivity (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.”

Prior to approval, the NDA was granted priority review for this indication in April 2021 and breakthrough therapy designation in April 2020.3


  1. Takeda’s EXKIVITY™ (mobocertinib) approved by U.S. FDA as the first oral therapy specifically designed for patients with EGFR Exon20 insertion+ NSCLC. News release. Takeda Pharmaceutical Company Limited. September 15, 2021. Accessed, September 15, 2021.
  2. FDA Approves Tissue-Based NGS Companion Diagnostic for Takeda's Targeted Therapy for NSCLC Patients with EGFR Exon20 Insertion Mutations. News release. Thermo Fisher Scientific. September 15, 2021. Accessed September 16, 2021.
  3. 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 September 15, 2021.
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