Mobocertinib Demonstrates Clinically Meaningful Activity Compared With Real-World Data in Advanced EGFR Exon 20 Insertion+ NSCLC


For patients with advanced EGFR Exon 20 Insertion–positive non–small cell lung cancer, mobocertinib appears to yield clinically meaningful activity compared with real-world data.

Novel EGFR tyrosine kinase inhibitor (TKI) mobocertinib (Exkivity) yielded improved responses vs real-world data in a population of patients with non–small cell lung cancer (NSCLC) who are positive for EGFR exon 20 insertion mutations following treatment with frontline platinum-based chemotherapy, according to findings from a multicenter, open-label clinical trial that were presented during the 2021 ESMO Congress.1

Results showed that the weighted response rate was nearly 3 times higher with mobocertinib vs standard of care, and both progression-free survival (PFS) and overall survival (OS) were significantly prolonged with mobocertinib compared with treatment options used in the real-world setting, according to Sai-Hong I. Ou, MD, PhD, from the Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, and colleagues who presented the results in a poster presentation.

After propensity score weighting, the confirmed ORR for 114 patients treated with mobocertinib in the study was 35.1% (95% CI, 26.4%-44.6%) vs 11.9% (95% CI, 5.8%-18.0%) in the real-world group, an absolute difference of 23.2% (odds ratio [OR], 3.75; 95% CI, 2.05-6.89; P <.01).

The weighted median PFS was longer in mobocertinib-treated patients in the trial, at 7.3 months (95% CI, 5.6-8.8) compared with 3.3 months (95% CI, 2.2-7.3) in the real-world group (HR, 0.57; 95% CI, 0.36-0.90; P = .0138).

After weighting, the median OS for the mobocertinib group and RWD group was 24.0 months (95% CI, 14.6-28.8) and 12.4 months (95% CI, 7.1-16.6), respectively (HR, 0.53; 95% CI, 0.33-0.83; P = .0089).

The data come on the heels of the September 2021 FDA approval of mobocertinib for the treatment of adult patients with locally advanced or metastatic EGFR exon 20 insertion–mutant metastatic NSCLC, as detected by an FDA-approved test, and who have received prior platinum-based chemotherapy.

“Among platinum-pretreated patients with EGFRex20ine+ NSCLC, mobocertinib demonstrated significantly higher ORR, prolonged PFS and OS compared with treatment options used in the real-world setting, even after propensity score weighting,” the investigators noted.

EGFR exon 20 insertion mutations are present in 4% to 12% of patients with EGFR-mutant NSCLC. Standard frontline treatment in this setting is platinum-based chemotherapy, but outcomes are poor, representing an unmet need, according to the investigators. Mobocertinib is designed to selectively target in-frame EGFR exon 20 insertion mutations in NSCLC.

In an ongoing phase 1/2 trial (NCT02716116), mobocertinib demonstrated clinically meaningful benefit in platinum-pretreated patients with EGFR exon 20 insertion–mutant metastatic NSCLC, which was the basis for the September 2021 FDA approval in this setting.2

The study presented during the 2021 ESMO Congress compared clinical outcomes for platinum-pretreated patients with EGFR exon 20 insertion–mutant metastatic NSCLC who were treated with mobocertinib at 160 mg daily, as part of the phase 1/2 trial, vs standard of care in the post-platinum second- or later-line setting using data from 50 patients identified from the Flatiron Health electronic record database.

Because of the rarity of patients with NSCLC who have EGFR exon 20 insertion mutations, conducting a controlled clinical trial with a comparator arm is difficult; therefore, the investigators chose to use real-world data as a comparator.

The median age of participants was 60.0 years in the mobocertinib group and 64.0 years in the real-world group. Females represented 65.8% and 68.0% of the groups, respectively. A smoking history was present in 28.9% and 42.0%, respectively, and 35.1% and 34.0%, respectively, had brain metastases at baseline.

In the real-world group, second- or later-line standard-of-care treatment consisted of an EGFR TKI in 20.0%, immunotherapy alone in 40.0%, and chemotherapy with or without immunotherapy or monoclonal antibody in 40.0%.

The analysis was conducted in an unadjusted data set and in a set using propensity score modeling with inverse probability of treatment weightings to balance prognostic factors for NSCLC between patients in the mobocertinib and real-world data groups.

In the unweighted dataset, the confirmed ORR (P < .01), median PFS (P = .0072), and OS (P = .0053) were all significantly superior in patients on the mobocertinib arm compared with the real-world group, and notable differences remained following propensity weighting.

“Despite differences between controlled trial data and real-world data, in the absence of direct head-to-head trial data, real-world can be used as a comparator for single-arm clinical trials,” the investigators added.


  1. OuS-H I, Lin HM, Hong J-L, et al. Indirect comparison of mobocertinib and standard of care in platinum-pretreated patients with NSCLC with EGFR exon 20 insertion. Presented at: 2021 ESMO Congress; September 16-21, 2021; virtual. Abstract 1211P.
  2. Ramalingam SS, Zhou C, Kim TM, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic NSCLC (mNSCLC): additional results from platinum-pretreated patients (pts) 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
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