FDA Approves Mobocertinib for EGFR Exon 20-Positive mNSCLC

The FDA has granted approval to mobocertinib for the treatment of adult patients with locally advanced or metastatic EGFR exon 20 insertion–mutant metastatic non–small cell lung cancer, as detected by an FDA-approved test, and who have received prior platinum-based chemotherapy.

The FDA has granted approval to mobocertinib (Exkivity) for the treatment of adult patients with locally advanced or metastatic EGFR exon 20 insertion–mutant metastatic non–small cell lung cancer (mNSCLC), as detected by an FDA-approved test, and who have received prior platinum-based chemotherapy, announced Takeda Pharmaceuticals, in a press release.1

The first-in-class oral tyrosine kinase inhibitor (TKI) approval represents the first oral therapy specifically designed to selectively target EGFR exon 20 insertion mutations. Results from a phase 1/2 study (NCT02716116) of mobocertinib serve as basis for the FDA’s decision.

EGFR exon 20 insertion-positive NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi A. Jänne, MD, PhD, Dana Farber Cancer Institute, in a press release. “The approval of Exkivity 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.”

Suresh S. Ramalingam, MD, FASCO, presented the most recent study results during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. In the study mobocertinib induced rapid, deep, and durable responses and showed a tolerable safety profile in patients with platinum-pretreated EGFR exon 20 insertion–positive mNSCLC.2

Of 144 patients with platinum-pretreated disease who received mobocertinib, the confirmed overall response rate (ORR) by independent review committee (IRC) assessment was 28% (95% CI, 20%-37%), which were all responses partial responses (PRs). By investigator assessment, the confirmed ORR was 35% (95% CI, 26%-45%), with complete responses (CRs) in fewer than 1% of patients, and PRs in 34%.

The median duration of response (DOR) observed with mobocertinib treatment in the study 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 study included roughly100 patients with EGFR exon 20-positive mNSCLC, and later access to the investigational drug was expand to what is referred to as the EXCLAIM cohort. The group consists of patients who received prior platinum-based therapy, had refractory EGFR exon 20 insertion–positive mNSCLC, and no active or measurable central nervous system metastases.

At baseline, the median age of patients was 60 years old (range, 27-84). Sixty-six percent of the population was female. The majority of patients were of Asian descent (60%). Most patients had adenocarcinoma histology (98%) and an ECOG performance status of 1 (75%). Also, most patients had no history of smoking (71%).

The median number of prior anticancer regimens was 2. All patients enrolled received prior platinum-based chemotherapy, 43% received prior immunotherapy, and 25% received prior EGFR TKIs. Baseline screening also identified brain metastases in 35% of patients.

Mobocertinib was administered at 160 mg in the study. In the study population, this dose level was found to be safe and consistent with other EGFR TKIs.

In the platinum-pretreated patient cohort, 100% of patients reported any-grade adverse events (AEs), and 99% of patients had treatment-related AEs (TRAEs) of any grade. Grade 3 or greater AEs were seen in 69% of patients and grade 3 or greater TRAEs were observed in 47% of patients.

There were serious AEs observed in 49% of patient in the study, and 46% of the serious AEs were grade 3 or greater n severity. Twenty-five percent of the population experienced an AE that led to dose reduction and there were treatment discontinuations in 17%. The most commonly reported AEs that led to treatment discontinuation in this cohort included diarrhea (4%), nausea (4%), vomiting (2%), decreased appetite (2%), and stomatitis (2%).

“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,” said Teresa Bitetti, president, Global Oncology Business Unit, Takeda, in a press release.1 “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.”


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 Pharmaceuticals. Septemebr 15, 2021. Accessed September 15, 2021.

2. Ramalingam SS, Zhou C, Kim TM, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion+ metastatic NSCLC: additional results from platinum-pretreated patients and EXCLAIM cohort of phase 1/2 study. J Clin Oncol. 2021;39(suppl 15):9014. doi:10.1200/JCO.2021.39.15_suppl.9014