FDA Grants Priority Review to Mobocertinib for EGFR Ex20 Insertion mNSCLC

Christopher Arendt, PhD

The FDA has granted a priority review to mobocertinib (TAK-788) as a treatment for adult patients with 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, according to a press release from Takeda Pharmaceutical.¹

Mobocertinib, a first-in-class oral tyrosine kinase inhibitor (TKI) is the first oral therapy specifically designed to selectively target EGFR exon 20 insertion mutations.

“Patients with EGFR exon 20 insertion+ mNSCLC face considerable challenges, as current treatment options provide limited benefit, resulting in poor survival outcomes,” said Christopher Arendt, PhD, head, Oncology Therapeutic Area Unit, Takeda. “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 supporting the new drug application come from a phase 1/2 trial of mobocertinib in patients with mNSCLC. The study included a dose-escalation phase looking at mobocertinib monotherapy as well as the TKI in combination with chemotherapy, and expansion and extension cohorts explored mobocertinib in patients with mNSCLC harboring EGFR exon 20 insertion mutations.

The platinum-pretreated population cohort analysis included 114 patients with EGFR exon 20 insertion–mutant metastatic NSCLC who had received prior platinum-based therapy and were treated with mobocertinib at a 160-mg, once-daily dose in the dose-escalation and -expansion phases of the study.

According to data presented at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer,² patients in this cohort had a median age of 60 (range, 27-84), 66% were female, and 60% were of Asian descent. Thirty-two percent of patients had received at least 2 prior systemic lines of anticancer therapy (range, 1-7). Moreover, the median time on treatment was 7.0 months (range, 0-31).

The confirmed objective response rate (ORR) by independent review committee (IRC) assessment 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 by both IRC and investigator assessment.

Mobocertinib resulted in reductions of target lesions volume, with 82% of patients experiencing a reduction from baseline in the sum of the target lesion diameter.

The safety profile for mobocertinib was considered manageable. Common treatment-related adverse events (TRAEs; ≥20%) in platinum-pretreated patients included diarrhea (90%), rash (45%), paronychia (34%), nausea (32%), decreased appetite (32%), dry skin (30%) and vomiting (30%). Grade 3 or higher TRAEs (≥5%) included diarrhea (21%). Nineteen patients (17%) discontinued due to AEs, most commonly due to diarrhea (4%), nausea (4%), vomiting (2%), decreased appetite (2%), and stomatitis (2%).

The new drug application for mobocertinib is up for potential accelerated approval and also for concurrent international review through Project Orbis. Previously, the FDA also granted mobocertinib with a breakthrough therapy designation in this setting.

The developer of mobocertinib, Takeda, has also established an Expanded Access Program (NCT04535557) for patients to receive access to mobocertinib during the application review period.

_References

_{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 Pharmaceutical Company Limited. April 27, 2021. Accessed April 28, 2021. https://bit.ly/3aIjVhZ}

_{2. Zhou C, Ramalingam S, Li B, et al. Mobocertinib in NSCLC with EGFR exon 20 insertions: results from EXCLAIM and pooled platinum-pretreated patient populations. Presented at: International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer; January 28-31, 2021; virtual.}